Difference between revisions of "Timeline of calorie restriction"

Latest revision as of 18:51, 1 October 2024

This is a timeline of calorie restriction, attempting to describe significant events in the history of the topic, especially concerning scientific research. Many of the events described in this timeline are illustrative of a much greater body of research on calorie restriction.

Sample questions

The following are some interesting questions that can be answered by reading this timeline:

How and when was the concept of calorie established? What are some foundational events describing its discovery?
- Sort the full timeline by "Event type" and look for the group of rows with value "Background".
- You will mostly see early events in the field of bioenergetics establishing the existence and concept of calorie.
What are some notable research cases involving calorie restriction?
- Sort the full timeline by "Event type" and look for the group of rows with value "Research".
- For calorie restriction effect type in the organism, sort the full timeline by "Calorie restriction effect type (when applicable)".
- You will see a variety of effects, ranging from behavior to health and longevity.
What are some species having been studied in calorie restriction research?
- Sort the full timeline by "Research subject species (when applicable)".
- You will mostly see lab research in rodents. Other species, from nematodes to monkeys, are also mentioned.
What are beneficial and what are harmful results for the organism in calorie restriction research?
- Sort the full timeline by "Effect direction (when applicable)".
- You will mostly see research cases concluding in beneficial results for subjects, most often rodents, but also other species. Harmful results are also described. Helpful results in humans are often in the form of advocacy rather than research.
What are some books covering the topic of calorie restriction?
- Sort the full timeline by "Event type" and look for the group of rows with value "Literature".

Other events are described under the following types: "Concept development", "Diet introduction", "Notable case", "Organization", "Policy", and "Recommendation".

Big picture

Time period	Development summary	More details
19th century	Basic science	The concept of calorie is developed in this time. The concept of calorie restriction is practically non-existent.
20th century (first half)	Basic concept and first discoveries	In the early century, Carlo Moreschi becomes the first to describe the effects of calorie restriction on cancer prevention. This would be followed by a large body of work demonstrating calorie restriction tumor preventive effects in various animal models.^[1] However, the basic concept of calorie restriction is founded in the late 1930s.^[2] In that same decade, calorie restriction possible impact on the growth and health of children becomes an important topic, while mechanisms that underlie aging are not on the radar screen yet.^[3] Since the late 1930s, the term calorie restriction becomes more widely used. In the 1940s, many researchers report that calorie restriction retards or prevents the onset of age-related diseases such as kidney disease, tumors, and leukemia.^[2]
20th century (second half)	Increased link to longevity and clinical introduction	From the 1950s towards the 1980s, the longevity effect of calorie restriction is reported in multiple species.^[2] Beginning in the 1970s, research on calorie restriction and aging markedly intensifies.^[4] Around the late 1970s and early 1980s, a resurgence in interest begins in the potential of calorie restriction to extend life. The work of Roy Walford in the United States is notable at this time.^[5] In the 1980s, the very-low-calorie diet starts being used for clinical purposes.^[6]
1990s onwards	Modern approach	Molecular biology is increasingly put to use in the effort to understand the basis of the actions of calorie restriction. Prior to it, morphological pathology and physiology were the primary tools used to explore CR.^[7]

Full timeline

Year	Event type	Calorie restriction effect type (when applicable)	Effect direction (when applicable)	Research subject species (when applicable)	Details	Location/researcher affiliation
1819–1824	Background				The calorie is first introduced by French chemist Nicolas Clément, as a unit of heat energy, in lectures during these years.^[8]^[9]	France
1879	Background				French chemist Marcellin Berthelot distinguishes between gram-calorie (modern calorie) and kilogram-calorie (modern kilocalorie).^[8]	France
1887	Background				The use of the kilogram-calorie (kcal) for nutrition is introduced in the United States by American chemist Wilbur Olin Atwater, a professor at Wesleyan University.^[9]	United States (Wesleyan University, Connecticut)
1896	Background				The modern calorie (cal) is first recognized as a unit of the centimetre–gram–second system of units (cgs).^[8]
1909	Research	Health (cancer)	Helpful	Rodent (rat)	Italian immunologist in Germany Carlo Moreschi finds that tumors transplanted into rats that were underfed did not grow as well as those transplanted into Ad libitum fed rats. This is the first hint that calorie restriction may have an effect on tumor progression.^[5]	Germany
1914	Research	Health (cancer)	Helpful	Rodent	American virologist Francis Peyton Rous reports that reducing food intake inhibits the occurrence of spontaneous cancers in rodents.^[10]^[11]	United States
1917	Research	Lifespan and mortality	Helpful	Rodent (rat)	American biochemists Thomas Osborne and Lafayette Mendel publish the first scientific study showing that restricting food extends life.^[12]	United States (Yale University, New Haven, Connecticut)
1918	Literature	Weight loss	Helpful	Human	American doctor Lulu Hunt Peters publishes Diet & Health: With Key to the Calories, which is aimed at women and presents the concept of calorie reduction as the best form of weight loss and watching weight.^[13]
1920	Research	Longevity	Harmful	N/A	In opposition to 1917 report by Osborne and Mendel, T. Robertson and L.A. Ray publish scientific study concluding that restricting food shortens life.^[14]^[12]	Australia (University of Adelaide), Canada (University of Toronto)
1925	Background				The calorie starts being defined in terms of the joule.^[15]
1935	Research	Longevity	Helpful	Rodent (rat)	American biochemist Clive McCay and his colleagues publish a seminal paper, which shows that slowing the post-weaning growth of rats by markedly restricting their food intake significantly increases their longevity.^[7] This is the first widely known scientific publication on the impact of dietary restriction on life expectancy.^[16]^[17]^[18]	United States
1935	Research	Organ level effect (bone)	Harmful	Rodent (rat)	Study by Clive McCay and colleagues reports that calorie restriction results in extremely brittle femurs.^[18]	United States
1935	Research	Longevity	Helpful	Rodent (rat)	Clive McCay and colleagues publish a landmark paper in the Journal of Nutrition entitled The effect of retarded growth upon the length of life span and upon the ultimate body size which provides the first systematic research evidence that calorie restriction prolongs life.^[19]^[3]
1939	Research	Longevity	Neutral	N/A	C.M. McCay and colleagues publish a paper that defines for the first time the aging research value of the calorie restriction model, suggesting that calorie restriction may be a model for studying aging: “Retardation of growth by diets, complete except for calories, affords a means of producing very old animals for studying aging”.^[20]	United States (Cornell University, Ithaca, New York)
1942	Research	Health (cancer)	Helpful	Human	Albert Tannenbaum writes: “It follows that the avoidance of overweight through restriction of food intake may aid in the prevention of human cancer or at least delay its onset”.^[3]
1947	Research	Lifespan and mortality	Helpful	Rodent (mouse)	Research by Ball and colleagues reports that lifelong dietary restriction dramatically extends the life span of mice (a maximum life span of 850 days vs. 550 days), whereas dietary restriction for the first 240 days has little effect.^[12]
1948	Background				The current definition of the calorie is formally adopted as equivalent to approximately 4.2 joules.^[15]
1951	Research	Organ level effect (heart)	Helpful	Human	Study by Strom and Jensen recognizes beneficial effects of calorie restriction on heart function as a result of shortage of food during World War II.^[21]	Norway
1951	Research	Lifespan and mortality	Helpful	Tokophrya infusionum	Study by Maria A. Rudzinska reports that calorie restriction decreases the mortality rate in Tokophrya infusionum (protozoan).^[22]	United States (New York University)
1960	Research	Lifespan and mortality	Helpful	Rodent (rat)	Study by Benjamin N. Berg and Henry S. Simms published in the Journal of Nutrition proposes link between life extension and reduction in body fat content.^[23]^[7]	United States
1961	Research	Lifespan and mortality	Helpful	Rodent (brown rat)	Study by M.H. Ross reports on calorie restriction decreasing the mortality rate in Rattus norvegicus (rat).^[24]	United States (Biochemical Research Foundation, Newark, Delaware)
1963	Research	Lifespan and mortality	Helpful	Fish	Study by Alex Comfort reports that retarding the growth of fish by restricting food increases their longevity.^[25]	United Kingdom (University College London)
1965	Research	Lifespan and mortality	Helpful	Rotifer (Philodina acuticornis)	Study by D.D. Fanestil and C.H. Barrows Jr reports on calorie restriction decreasing the mortality rate in Philodina acuticornis, a species of freshwater bdelloid rotifers.^[26]
1973	Research	Health (immune system)	Helpful	Rodent	Study by American pathologist Roy Walford et al. in rodents using intermitent fasting protocol to explore the humoral responses of subjects reports that after 1 year of restriction, Immunoglobulin M and Immunoglobulin G antibodies activity was augmented.^[27] Being among the first to study the effects of calorie restriction on immune function in rodents, Walford would become a strong advocate for the use of calorie restriction in humans.^[5]	United States (UCLA School of Medicine, Los Angeles)
1977	Research	Metabolic effect	Helpful	N/A	American biologist George A. Sacher proposes that calorie restriction retards aging by decreasing the intensity of energy metabolism.^[4]	United States (Argonne National Laboratory)
1977	Research	Lifespan and mortality	Helpful	Nematode (Caenorhabditis elegans)	Study by M.R. Klass reports on calorie restriction decreasing the mortality rate in C. elegans.^[28]	United States (University of Colorado Boulder)
1978	Notable case	Mortality	Harmful	Human	In this year, 58 people die in the United States after following very-low-calorie liquid protein diets.^[29]	United States
1980	Research	Organ level effect (white adipose tissue)	Helpful	Rodent (rat)	Study by Helen A. Bertrand et al. in rats reports that, under calorie restriction, the loss of white adipose tissue is disproportionately large.^[30]	United States
1980	Research	Lifespan and mortality	Helpful	Rodent (Mus musculus)	Study by K.E. Cheney and colleagues reports on calorie restriction decreasing the mortality rate in house mice.^[31]	United States (University of California, Los Angeles)
1982	Research	Lifespan and mortality	Helpful	Rodent (mouse)	Study by Richard Weindruch and Roy Walford in 12- to 13-month-old mice on food restriction by using nutrient-enriched diets in accordance with the concept of "undernutrition without malnutrition" results in the mice on the restricted diet averaging 10 to 20 percent increases in mean and maximum survival times compared to the control mice.^[5]^[32]	United States
1984	Policy	Illness	Harmful	Human	The United States FDA starts requiring that very-low-calorie diets providing fewer than 400 calories a day to carry a warning that they can cause serious illness and need to be followed under medical supervision.^[29]	United States
1984	Literature	Lifespan and mortality	Helpful	Human	Roy Walford publishes Maximum Life Span a book on lifespan determination advocating calorie restriction.^[5]
1984	Research	Organ level effect (bone)	Helpful	Rodent (rat)	Research by Kalu et al. in rats concludes that calorie restriction completely prevents the senile bone loss recorded in ad libitum rats with femur strength to body weight ratios greater than in ad libitum.^[33]	United States (University of Texas Health Science Center at San Antonio)
1986	Literature	Lifespan and mortality	Helpful	Human	Richard Weindruch and Roy Walford publish The Retardation of Aging and Disease by Dietary Restriction, an influential and comprehensive encyclopedia of calorie restriction studies that would encourage many scientists to become interested in, and to investigate, calorie restriction and its impact on aging.^[19]	United States
1986	Literature	Lifespan and mortality	Helpful	Human	Roy Walford publishes The 120-Year Diet: How to Double Your Vital Years, advocating the use of calorie restriction to increase human longevity.^[5]^[34]	United States
1987	Research	Behavior (physical activity)	Helpful	Rodent	Study by D E Harrison and J R Archer reports that the response shown by many rodents to calorie restriction is actually to increase levels of activity.^[35]^[5]
1988	Literature	Lifespan and mortality	Helpful	Human	Roy Walford and Richard Weindruch publish The Retardation of Aging and Disease by Dietary Restriction.^[5]	United States
1991–1993	Diet introduction		Helpful	Human	Roy Walford's compiled data during his participation in Biosphere 2 is used to develop the CRON-diet, jointly with Lisa Walford, and Brian M. Delaney. IT consists in eating a diet low in fat and in calories but "nutrient-dense".^[36]^[37]	United States
1993	Research	Organ level effect (liver)	N/A	Rodent (rat)	Research by Alterman et al. in rats shows that calorie restriction has profound effects on the hepatic microsomal levels and activities of cytochrome P-450s, a superfamily of enzymes containing heme as a cofactor that functions as monooxygenases.^[38]	United States (Texas A&M University)
1994	Organization	Lifespan and mortality	Helpful	Human	The Calorie Restriction Society is founded. This organization sponsors conferences, funds anti-aging research, and offers practical guidance to its members.^[39]	United States
1994	Research	Health (cancer)	Helpful	Rodent (mouse)	Study by Peter P. Fu and colleagues shows that caloric restriction profoundly inhibits liver-tumor formation after initiation by 6-nitrochrysene in male-mice.^[40]^[5]	United States (National Center for Toxicological Research, Arkansas)
1994	Research	Metabolic effect (oxidative stress)	Helpful	Rodent (mouse)	Study by R.S. Sohal and colleagues in mice reports that isolated mitochondria from subjects under calorie restriction show reductions in superoxide radical production.^[41]	Unted States (Southern Methodist University, Dallas)
1995	Research	Behavior (cognitive effect)	Neutral	N/A	Study by M.W. Green et al. concludes that short-term food deprivation has little or no detrimental effect on cognitive function, also indicating that "deficits in cognitive function found to be associated with spontaneous dieting are unlikely to be due primarily to any direct physiological or nutritional effects of food deprivation".^[42]	United Kingdom (Institute of Food Research, Reading, Berkshire)
1995	Literature	Longevity	Helpful	Human	Roy Walford publishes The Anti-Aging Plan, which promotes calorie restriction in humans.^[5]
1995	Research	Endocrine effect (leptin and other adipokines)	Harmful	Rodent (mouse)	Study by Robert C. Frederich and colleagues in mice shows that the loss of body fat during calorie restriction results in profound reductions in circulating levels of several adipokines, including leptin.^[43]	United States (Beth Israel Hospital, Boston, Massachusetts)
1996	Research	Metabolic effect (oxidative stress)	Helpful	Rodent	Study by B.P. Yu in mice concludes that calorie restriction in subjects reduces oxidative stress.^[44]	United States (University of Texas Health Science Center, San Antonio)
1997	Research	Health (cancer)	Helpful	Rodent	Study by Hart and Turturro in rodents reports that calorie restriction in subjects reduces the susceptibility to cancer.^[45]	United States (National Center for Toxicological Research, Jefferson, Arkansas)
1997	Research	Organ level effect (alimentary tract)	Helpful	Rodent (mouse)	Study by Casirola et al. in mice reports that intestinal nutrient uptake in calorie restriction animals is significantly higher for D-sugars, L amino acids and L-glucose than in same-age ad libitum animals.^[46]	United States (University of Medicine and Dentistry of New Jersey)
1997	Research	Organ level effect (muscle)	Helpful	Rodent (mouse)	Study by Aspnes et al. in mice reports that calorie restriction has a protective effect against sarcopenic muscle loss in subjects.^[47]	United States (University of Wisconsin–Madison)
1998	Research	Health (cancer)	Helpful	Rodent (rat)	Study by T.J. Spady et al. shows that dietary energy restriction abolishes development of prolactin-producing pituitary tumors in rats treated with 17 beta-estradiol.^[48]	United States (University of Nebraska Medical Center, Omaha)
1998	Concept development				The term caloric restriction mimetic is coined by Lane, Ingram, and Roth, of the National Institute on Aging in a seminal paper in the Journal of Anti-Aging Medicine, the forerunner of Rejuvenation Research.^[49]	United States (National Institute on Aging, Maryland)
1998	Research	Health	Neutral	Human	Verdery and Walford show that calorie restriction in humans produces physiological effects that are similar to those found in rodents and monkeys.^[50]
1998	Research	Metabolic effect (oxidative stress)	Helpful	Rodent (rat)	Study by M.V. Aksenova and colleagues in rats concludes that calorie restriction relieves age-associated levels of oxidative stress and lessen protein damage in the brain.^[51]	United States (University of Kentucky)
1998	Research	Health (insulin resistance and metabolic syndrome)	Helpful	Rodent (rat)	Research by Barzilai et al. in rats shows that calorie restriction for 18 months restores hepatic insulin sensitivity to the same levels observed in young rats (4 months). Aging is accompanied by a marked increase in hepatic resistance to the action of insulin.^[52]	United States (Albert Einstein College of Medicine, New York)
1999	Research	Health (cancer)	Neutral	Rodent (mouse)	Study by Pugh et al. in mice shows that calorie restriction performed from the age of 12 months onwards resunts in the incidence of the most prevalent cancer (plasma cell neoplasm) being higher in calorie restricted mice (66%) than in controls (41%). However calorie restriction is found to increase the age at which tumor-bearing mice died, also reducing the percentage of mice dying with cancers, suggesting that CR retards the promotion and/or progression of existing lymphoid cancers.^[53]	United States (Institute on Aging, University of Wisconsin–Madison)
1999	Research	Mortality	Helpful	Monkey	Study by Roth et al. in monkeys suggests that mortality is reduced in subjects on calorie restriction.^[54]^[55]	United States (National Institute of Aging, National Institutes of Health, Baltimore, Maryland)
2000	Literature	Longevity	Helpful	Human	R.L. Walford publishes Beyond the 120-Year Diet: How to Double Your Vital Years, which argues that longevity can be significantly increased by a diet that contains all the required nutrients but about a third fewer calories.^[5]
2000	Research	Metabolic effect (autophagy)	Helpful	Rodent (rat)	Study by G.Cavallini and colleagues in rats reports that calorie restriction prevents the age-dependent decline of autophagic proteolysis and improves the sensitivity of liver cells to stimulation of lysosomal degradation.^[56]	Italy (Dipartimento di Patologia sperimentale, Biotecnologie mediche, Infettivologia e Epidemiologia, Pisa)
2000	Research	Health (disease)	Helpful	Monkey	Study by Black et al. in monkeys suggests that morbidity, in particular neoplastic disease, is reduced in subjects on calorie restriction.^[55]
2001	Research	Organ level effect (bone)	Harmful	Monkey	Study by Black et al. reports that short term (1 year) calorie restriction in young, 4 years old, male monkeys delayed skeletal maturation and reduced bone mass whereas adult-onset calorie restriction, 19 years old, had no significant effect on bone mass compared with control male monkeys.^[57]	United States (Gerontology Research Center, National Institute on Aging, Baltimore)
2001	Research	Organ level effect (skin)	Helpful	Rodent (rat)	Research by N.M. Elsayed in rodents reports that oxidative protection of the lung tissue is enhanced by calorie restriction and rats under CR exposed to ozone show lowered oxidative damage and elevated survivability.^[58]	United States (Walter Reed Army Institute of Research, Washington, D.C.)
2001	Research	Health (obesity)	Helpful	Human	A review by P. Mustajoki and T. Pekkarinen finds that the very-low-calorie diet in the treatment of obesity has no serious harmful effect when done under medical supervision, for periods of 8–16 weeks with an average weight loss of 1.5-2.5 kg/week.^[6]	Finland (Peijas Hospital, Department of Medicine, Vantaa)
2001	Research	Behavior (reproduction)	Harmful	Rodent	Research by Caprio et al. in rodents reports that when female animals are under calorie restriction their fertility is reduced, presumably as a mechanism to prevent them becoming pregnant at a time when insufficient resources are available to support a reproductive event.^[59]	Italy (Universita’ di Tor Vergata, Università La Sapienza)
2002	Research	Behavior (hunger)	Neutral	Human	Study by Hansen et al. reports that circulating levels of ghrelin, an orexigenic hormone secreted by the stomach, is increased in the plasma during diet induced weight loss in obese humans, suggesting that ghrelin may contribute to the sustained appetite associated with calorie restriction.^[60]^[5]	Denmark (Aarhus University Hospital), Japan (National Cardiovascular Center Research Institute, Osaka)
2002	Research	Longevity	Helpful	Multiple species	According to paper by Lane et al., there are more than 2,000 animal studies on calorie restriction showing dramatic results across many different species, which provide good evidence that restricting calories slows down aging and can extend youthfulness.^[50]
2003	Research	Lifespan and mortality	Harmful	Rodent	Research in rodents by Forster et al. shows that the effect of calorie restriction may be negative if the restriction is started very late in life.^[61]	United States (Institute for Aging and Alzheimer's Disease Research, University of North Texas Health Science Center at Fort Worth)
2003	Research	Endocrine effect (ghrelin)	Neutral	Rodent (rat)	Research by Barazzoni et al. in rats concludes that during calorie restriction, levels of ghrelin are increased.^[62]	Italy (Dipartmento di Scienze Cliniche, Morfologiche e Technologiche-DSCMT, Clinica Medica, Trieste)
2003	Research	Health (cancer)	Helpful	Rodent (mouse)	A systematic metaanalysis by Dirx et al. of 14 studies in mice suggests that subjects on calorie restriction develop between 41% and 69% less mammary tumors than the control groups.^[63]	Netherlands (Maastricht University)
2003	Research	Organ level effect (bone)	Harmful	Rodent (rat)	Research by LaMothe et al. in rats concludes that axial and appendicular bones are adversely influenced by calorie restriction in late-middle-aged subjects in different manners.^[64]
2003	Research	Longevity	Helpful	Rodent (mouse)	Research by Matthias Blüher et al. in mice suggests that reduced fat mass without calorie restriction can be associated with increased longevity.^[65]	United States (Harvard Medical School, Boston)
2003	Research	Organ level effect (liver)	Harmful	Rodent (rat)	Study by U.M. Apte reports rats under calorie restriction showing increased susceptibility to liver damage induced by the hepatotoxicant thioacetamide.^[66]	United States
2003	Research	Endocrine effect (adiponectin	Harmful	Rodent (mouse)	Study by Combs et al. in mice reports increased levels of adiponectin by calorie restriction.^[67]	United States (Albert Einstein College of Medicine)
2004	Research	Health (immune system)	Helpful	Rodent (mouse)	Research by Christopher A Jolly shows that calorie restriction delays thymic involution in mice.^[68]	United States (The University of Texas at Austin)
2004	Research	Organ level effect (lungs)	Harmful	Rodent (rat)	Study by Massaro et al. in rats suggests that calorie restriction increases the risk of development of emphysema, a lung condition that causes shortness of breath.^[69]	United States (University of Texas Health Science Center)
2005	Research	Health (cancer)	Helpful	Rodent (mouse)	Study by Stewart and colleagues in mice shows that skin cancer promotion is inhibited by calorie restriction.^[70]	United States (Iowa State University)
2005	Research	Organ level effect (skin)	Helpful	Rodent (rat)	Research by Bhattacharyya et al. in rats concludes that calorie restriction retards age related changes on the skin along with increased collagen and elastic fibers, fibroblasts, and capillaries in skin samples from the subjects.^[71]	United States (University of Illinois at Chicago)
2005	Research	Endocrine effect (insulin)	Neutral	Rodent (mouse)	Research by Argentino et al. in mice reports that calorie restriction reduces circulating levels of insulin-like growth factor 1 and insulin (and glucose).^[72]^[73]	Argentina (Instituto de Química y Fisicoquímica Biológicas (UBA-CONICET), Facultad de Farmacia y Bioquímica, Buenos Aires)
2005	Research	Metabolic effect (mitochondrial biogenesis)	Helpful	Rodent (mouse)	Study by Enzo Nisoli and colleagues reports that calorie restriction at 30% for 3 months results in mitochondrial biogenesis in the brain, heart, liver and particularly the adipose tissue of mice.^[74]	Italy, United Kingdom
2006	Research	Behavior (cognitive effects)	Helpful	Rodent (mouse)	Research by Martin et al. reports evidence suggesting that calorie restriction and intermittent fasting may benefit neurons by impinging upon fundamental metabolic and cellular signaling pathways that regulate life-span.^[75]
2006	Research	Behavior (reproduction)	Harmful	Rabbit	Study by Brecchia et al. reports that, in female rabbits, food deprived completely for 24 and 48 hours results in decline in fertility by 23.9 and 21.4% respectively, matched by major disturbances in the endocrine axis linked to reproduction.^[76]	Italy
2007	Research	Metabolic effect (oxidative stress)	Helpful	Rodent (rat)	Study by Cenk Aydin et al. in rats concludes that subjects on calorie restriction are protected against oxidative stress induced by swimming exercise in the liver, heart and kidney.^[77] Two years later, the researchers discover the same effects in the brain and lungs.^[78]	Turkey (Uludag University, Bursa)
2007	Research	Behavior (cognitive effects)	Neutral	Rodent (rat)	Research by Martin et al. in rats reports no consistent pattern of verbal memory, visual retention/memory, or attention/concentration deficits being found over 6 months, and the energy deficit by calorie restriction or exercise was not significantly associated cognitive test performance.^[79]
2007	Research	Organ level effect (alimentary tract)	Harmful	Rodent (mouse)	Study by Yang et al. in mice reports what is perhaps the most conspicuous change in the morphology of the alimentary tract under calorie restriction, which is the hypertrophy of the stomach observed in subjects.^[80]	United States (Louisiana State University System)
2007	Research	Longevity	Helpful	Human	Stydy by Speakman and Hambly calculates that if the lifespan effects observed in rodents translate faithfully to an effect in humans, then if a 48 year old engaged in 30% calorie restriction for 30 years, until the current mean life-expectancy of 78, they might expect to live only an extra 2.8 years because of the CR effect.^[81]
2007	Research	Organ level effect (kidney)	Helpful	Rodent	Research by Chen et al. in rodents concludes that calorie restriction attenuates increased susceptibility to kidney injury in old subjects.^[82]	United States (Texas A&M Health Science Center)
2008	Research	Health (cancer)	Helpful	Rodent (mouse)	Study by Wheatley et al. in mice suggests that although a low calorie diet does not induce weight loss, it may reduce colon cancer risk by lowering serum IGF-I levels.^[83]	United States (University of Texas at Austin)
2008	Research	Organ level effect (bone)	Harmful	Rodent (rat)	Research by Baek et al. in rats concludes that moderate caloric restriction may cause bone loss at susceptible bone sites to a similar degree as does the unloading effect of microgravity in astronauts.^[84]
2008	Research	Organ level effect (muscle)	Helpful	Non-human primate	Study by Colman et al. reports that calorie restriction has a protective effect against sarcopenic muscle loss in non-human primates.^[85]	United States (Wisconsin National Primate Research Center, University of Wisconsin-Madison)
2014	Recommendation				According to the NICE 2014 guidelines, the routine use of very-low-calorie diets is not recommended due to safety concerns, but this approach can be used under medical supervision if there is a clinical rationale for rapid weight loss in obese individuals, as part of a "multi-component weight management strategy" with continuous support and for a maximum of 12 weeks.^[86]
2018	Research	Health (brain)	Helpful/harmful	Grey mouse lemur	Researchers find that caloric restriction increases lifespan but affects brain integrity in grey mouse lemur primates.^[87]	France

Numerical and visual data

Mentions on Google Scholar

Year	calorie restriction	calorie restriction benefits	calorie restriction weight loss	calorie restriction longevity	calorie restriction oxidative stress
1980	444	236	714	67	53
1985	597	327	956	111	81
1990	778	544	1,280	176	164
1995	1,070	857	1,760	281	317
2000	1,880	1,500	2,850	559	1,230
2002	2,560	1,840	3,910	786	1,790
2004	3,380	2,550	4,600	1,120	2,260
2006	4,340	3,350	6,330	1,410	3,110
2008	5,500	4,080	8,020	1,780	4,090
2010	5,870	5,150	8,410	2,350	4,050
2012	7,620	9,170	10,900	2,820	5,240
2014	9,190	7,660	12,800	3,120	6,690
2016	9,110	8,240	13,000	3,140	6,400
2017	9,590	8,870	13,500	3,880	6,910
2018	9,840	9,280	14,200	3,570	7,220
2019	9,930	9,590	14,200	3,520	7,310
2020	12,000	10,100	13,400	3,760	7,420

Google Trends

The chart below shows Google Trends data for Calorie restriction (search term), from January 2004 to June 2021, when the screenshot was taken. Interest is also ranked by country and displayed on world map ^[88].

Google Ngram Viewer

The comparative chart below shows Google Ngram Viewer data for calorie restriction and caloric restriction, from 1900 to 2019.^[89]

Wikipedia Views

The chart below shows pageviews of the English Wikipedia article Calorie restriction, from July 2015 to May 2021.^[90]

Meta information on the timeline

How the timeline was built

The initial version of the timeline was written by User:Sebastian.

Funding information for this timeline is available.

Feedback and comments

Feedback for the timeline can be provided at the following places:

FIXME

What the timeline is still missing

Minnesota Starvation Experiment
Fluid restriction diet
Maybe more on how intermittent fasting and calorie restriction relate?
Relationship between calorie restriction and hormesis
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Category:Diets

Timeline update strategy

External links

References

↑ Brandhorst, Sebastian; Longo, Valter D. (2016). "Fasting and Caloric Restriction in Cancer Prevention and Treatment". Metabolism in Cancer. 207: 241–266. doi:10.1007/978-3-319-42118-6_12.
↑ ^2.0 ^2.1 ^2.2 Hwangbo, Dae-Sung; Lee, Hye-Yeon; Abozaid, Leen Suleiman; Min, Kyung-Jin (24 April 2020). "Mechanisms of Lifespan Regulation by Calorie Restriction and Intermittent Fasting in Model Organisms". Nutrients. 12 (4): 1194. doi:10.3390/nu12041194.
↑ ^3.0 ^3.1 ^3.2 McDonald, Roger B.; Ramsey, Jon J. (2010). "Honoring Clive McCay and 75 Years of Calorie Restriction Research". The Journal of Nutrition. 140 (7): 1205–1210. ISSN 0022-3166. doi:10.3945/jn.110.122804. Retrieved 26 February 2021.
↑ ^4.0 ^4.1 Masoro, E. J. (26 February 2003). "Subfield History: Caloric Restriction, Slowing Aging, and Extending Life". Science of Aging Knowledge Environment. 2003 (8): 2re–2. doi:10.1126/sageke.2003.8.re2.
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[Brandhorst-1] Brandhorst, Sebastian; Longo, Valter D. (2016). "Fasting and Caloric Restriction in Cancer Prevention and Treatment". Metabolism in Cancer. 207: 241–266. doi:10.1007/978-3-319-42118-6_12.

[Abozaid-2] 2.0 ^2.1 ^2.2 Hwangbo, Dae-Sung; Lee, Hye-Yeon; Abozaid, Leen Suleiman; Min, Kyung-Jin (24 April 2020). "Mechanisms of Lifespan Regulation by Calorie Restriction and Intermittent Fasting in Model Organisms". Nutrients. 12 (4): 1194. doi:10.3390/nu12041194.

[opiyu-3] 3.0 ^3.1 ^3.2 McDonald, Roger B.; Ramsey, Jon J. (2010). "Honoring Clive McCay and 75 Years of Calorie Restriction Research". The Journal of Nutrition. 140 (7): 1205–1210. ISSN 0022-3166. doi:10.3945/jn.110.122804. Retrieved 26 February 2021.

[Subfield_His-4] 4.0 ^4.1 Masoro, E. J. (26 February 2003). "Subfield History: Caloric Restriction, Slowing Aging, and Extending Life". Science of Aging Knowledge Environment. 2003 (8): 2re–2. doi:10.1126/sageke.2003.8.re2.

[Speakman-5] 5.00 ^5.01 ^5.02 ^5.03 ^5.04 ^5.05 ^5.06 ^5.07 ^5.08 ^5.09 ^5.10 ^5.11 Speakman, John R.; Mitchell, Sharon E. (June 2011). "Caloric restriction". Molecular Aspects of Medicine. 32 (3): 159–221. doi:10.1016/j.mam.2011.07.001.

[Mustajoki2001-6] 6.0 ^6.1 Mustajoki, P.; Pekkarinen, T. (February 2001). "Very low energy diets in the treatment of obesity". Obesity Reviews. 2 (1): 61–72. doi:10.1046/j.1467-789x.2001.00026.x.

[asqw-7] 7.0 ^7.1 ^7.2 Masoro, Edward J. (2010). "History of Caloric Restriction, Aging and Longevity". Calorie Restriction, Aging and Longevity. Springer Netherlands: 3–14. doi:10.1007/978-90-481-8556-6_1#:~:text=1.1+introduction,retarded+growth+on+life+span. Retrieved 26 February 2021.

[Hargrove-8] 8.0 ^8.1 ^8.2 Hargrove, James L (December 2007). "Does the history of food energy units suggest a solution to "Calorie confusion"?". Nutrition Journal. 6 (1): 44. doi:10.1186/1475-2891-6-44.

[Hist-9] 9.0 ^9.1 Hargrove, James L (2007). "Does the history of food energy units suggest a solution to "Calorie confusion"?". Nutrition Journal. 6 (44): 44. PMC 2238749. PMID 18086303. doi:10.1186/1475-2891-6-44.

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Difference between revisions of "Timeline of calorie restriction"

Latest revision as of 18:51, 1 October 2024

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@@ Line 10: / Line 10: @@
 *  What are some notable research cases involving calorie restriction?
 ** Sort the full timeline by "Event type" and look for the group of rows with value "Research".
-*** For calorie restriction effect type in the organism, the full timeline by "Calorie restriction effect type (when applicable)".
+** For calorie restriction effect type in the organism, sort the full timeline by "Calorie restriction effect type (when applicable)".
-*** You will see a variety of effects, ranging from behavior to health and longevity.
+** You will see a variety of effects, ranging from behavior to health and longevity.
+* What are some species having been studied in calorie restriction research?
+** Sort the full timeline by "Research subject species (when applicable)".
+** You will mostly see lab research in rodents. Other species, from nematodes to monkeys, are also mentioned.
+* What are beneficial and what are harmful results for the organism in calorie restriction research?
+** Sort the full timeline by "Effect direction (when applicable)".
+** You will mostly see research cases concluding in beneficial results for subjects, most often rodents, but also other species. Harmful results are also described. Helpful results in humans are often in the form of advocacy rather than research.
 * What are some books covering the topic of calorie restriction?
 ** Sort the full timeline by "Event type" and look for the group of rows with value "Literature".
@@ Line 31: / Line 37: @@
 |}
-== Numerical and visual data ==
+==Full timeline==
-=== Mentions on Google Scholar ===
 {| class="sortable wikitable"
-! Year
+! Year !! Event type !! Calorie restriction effect type (when applicable) !! Effect direction (when applicable) !! Research subject species (when applicable) !! Details !! Location/researcher affiliation
-! calorie restriction
-! calorie restriction benefits
-! calorie restriction weight loss
-! calorie restriction longevity
-! calorie restriction oxidative stress
 |-
-| 1980 || 444 || 236 || 714 || 67 || 53
+| 1819–1824 || Background || || || || The {{w|calorie}} is first introduced by French chemist {{w|Nicolas Clément}}, as a unit of {{w|heat}} energy, in lectures during these years.<ref name="Hargrove">{{cite journal |last1=Hargrove |first1=James L |title=Does the history of food energy units suggest a solution to "Calorie confusion"? |journal=Nutrition Journal |date=December 2007 |volume=6 |issue=1 |pages=44 |doi=10.1186/1475-2891-6-44}}</ref><ref name=Hist>{{cite journal|last=Hargrove|first=James L|title=Does the history of food energy units suggest a solution to "Calorie confusion"? |journal=Nutrition Journal |year=2007|volume=6|issue=44|pages=44|doi=10.1186/1475-2891-6-44 |pmid=18086303|pmc=2238749}}</ref> || {{w|France}}
 |-
-| 1985 || 597 || 327 || 956 || 111 || 81
+| 1879 || Background || || || || French chemist {{w|Marcellin Berthelot}} distinguishes between gram-calorie (modern calorie) and kilogram-calorie (modern kilocalorie).<ref name="Hargrove"/> || {{w|France}}
 |-
-| 1990 || 778 || 544 || 1,280 || 176 || 164
+| 1887 || Background || || || || The use of the kilogram-calorie (kcal) for nutrition is introduced in the United States by American chemist {{w|Wilbur Olin Atwater}}, a professor at {{w|Wesleyan University}}.<ref name=Hist/> || {{w|United States}} ({{w|Wesleyan University}}, {{w|Connecticut}})
 |-
-| 1995 || 1,070 || 857 || 1,760 || 281 || 317
+| 1896 || Background || || || || The modern {{w|calorie}} (cal) is first recognized as a unit of the {{w|centimetre–gram–second system of units}} (cgs).<ref name="Hargrove"/> ||
 |-
-| 2000 || 1,880 || 1,500 || 2,850 || 559 || 1,230
+| 1909 || Research || Health (cancer) || Helpful || {{w|Rodent}} ({{w|rat}}) || Italian immunologist in Germany {{w|Carlo Moreschi}} finds that tumors transplanted into rats that were underfed did not grow as well as those transplanted into ''{{w|Ad libitum}}'' fed rats. This is the first hint that calorie restriction may have an effect on tumor progression.<ref name="Speakman"/> || {{w|Germany}}
 |-
-| 2002 || 2,560 || 1,840 || 3,910 || 786 || 1,790
+| 1914 || Research || Health (cancer) || Helpful || {{w|Rodent}} || American virologist {{w|Francis Peyton Rous}} reports that reducing food intake inhibits the occurrence of spontaneous cancers in rodents.<ref>{{cite book |last1=Everitt |first1=Arthur V. |last2=Rattan |first2=Suresh I. S. |last3=Couteur |first3=David G. |last4=Cabo |first4=Rafael de |title=Calorie Restriction, Aging and Longevity |publisher=Springer Science & Business Media |isbn=978-90-481-8556-6 |url=https://books.google.com.ar/books?id=zWgEkmHwjo8C&pg=PA4&lpg=PA4&dq=%22Calorie+restriction%22+%22in+1900..1930%22&source=bl&ots=vldtO4AGUn&sig=ACfU3U1uZ05sGxTWAJ6_oV4JjgEO_sxvJw&hl=en&sa=X&ved=2ahUKEwjo68y4r5XoAhVGHbkGHcQRD2EQ6AEwC3oECA0QAQ#v=onepage&q=%22Calorie%20restriction%22%20%22in%201900..1930%22&f=false |language=en}}</ref><ref>{{cite journal |last1=Rous |first1=Peyton |title=THE INFLUENCE OF DIET ON TRANSPLANTED AND SPONTANEOUS MOUSE TUMORS |journal=Journal of Experimental Medicine |date=1 November 1914 |volume=20 |issue=5 |pages=433–451 |doi=10.1084/jem.20.5.433}}</ref> || {{w|United States}}
 |-
-| 2004 || 3,380 || 2,550 || 4,600 || 1,120 || 2,260
+| 1917 || Research || Lifespan and mortality || Helpful || {{w|Rodent}} ({{w|rat}}) || American biochemists [[w:Thomas Burr Osborne (chemist)|Thomas Osborne]] and {{w|Lafayette Mendel}} publish the first scientific study showing that restricting food extends life.<ref name="Handbook of the">{{cite book |title=Handbook of the biology of aging |date=2006 |publisher=Elsevier Academic Press |location=Amsterdam |isbn=9780120883875 |edition=6th}}</ref> || {{w|United States}} ({{w|Yale University}}, {{w|New Haven, Connecticut}})
 |-
-| 2006 || 4,340 || 3,350 || 6,330 || 1,410 || 3,110
+| 1918 || Literature || Weight loss || Helpful || {{w|Human}} || American doctor {{w|Lulu Hunt Peters}} publishes ''Diet & Health: With Key to the Calories'', which is aimed at women and  presents the concept of calorie reduction as the best form of weight loss and watching weight.<ref name=Lit>{{cite web |first=Emily |last=Temple |url=https://lithub.com/some-hilarious-illustrations-from-americas-first-bestselling-diet-book/ |title=Some Hilarious Illustrations from America’s First Bestselling Diet Book  |website=LitHub |date=January 15, 2019 }}</ref>
 |-
-| 2008 || 5,500 || 4,080 || 8,020 || 1,780 || 4,090
+| 1920 || Research || Longevity || Harmful || N/A || In opposition to 1917 report by Osborne and Mendel, T. Robertson and L.A. Ray publish scientific study concluding that restricting food shortens life.<ref>{{cite journal |last1=Robertson |first1=T.Brailsford |last2=Ray |first2=L.A. |title=EXPERIMENTAL STUDIES ON GROWTH |journal=Journal of Biological Chemistry |date=November 1920 |volume=44 |issue=2 |pages=439–453 |doi=10.1016/S0021-9258(18)86250-0}}</ref><ref name="Handbook of the"/> || {{w|Australia}} ({{w|University of Adelaide}}), {{w|Canada}} ({{w|University of Toronto}})
 |-
-| 2010 || 5,870 || 5,150 || 8,410 || 2,350 || 4,050
+| 1925 || Background || || || || The {{w|calorie}} starts being defined in terms of the {{w|joule}}.<ref name="Calorie vvv">{{cite web |title=Calorie {{!}} unit of measurement |url=https://www.britannica.com/science/calorie |website=Encyclopedia Britannica |access-date=7 July 2021 |language=en}}</ref> ||
 |-
-| 2012 || 7,620 || 9,170 || 10,900 || 2,820 || 5,240
+| 1935 || Research || Longevity || Helpful || {{w|Rodent}} ({{w|rat}}) || American biochemist {{w|Clive McCay}} and his colleagues publish a seminal paper, which shows that slowing the post-weaning growth of rats by markedly restricting their food intake significantly increases their longevity.<ref name="asqw"/> This is the first widely known scientific publication on the impact of dietary restriction on life expectancy.<ref name="Zainabadi">{{cite journal |last1=Zainabadi |first1=Kayvan |title=A brief history of modern aging research |journal=Experimental Gerontology |date=April 2018 |volume=104 |pages=35–42 |doi=10.1016/j.exger.2018.01.018}}</ref><ref>{{cite journal| vauthors = McCay CM, Crowell M |date=October 1934 |title=Prolonging the Life Span |url=https://www.jstor.org/stable/15813 |journal={{w|The Scientific Monthly}} |volume=39 |issue=5 |pages=405–414 |doi= |jstor=15813 |pmc= |pmid=}}</ref><ref name=wwwd>{{cite journal| vauthors = McCay CM, Crowell MF, Maynard LA |date=1 July 1935 |title=The Effect of Retarded Growth Upon the Length of Life Span and Upon the Ultimate Body Size |url=http://www.wealthandhealth.ltd.uk/over100/C.%20M.%20McCAY%201935.pdf |journal={{w|The Journal of Nutrition}} |volume=10 |issue=1 |pages=63–79 |doi=10.1093/jn/10.1.63 |pmc= |pmid=}}</ref> || {{w|United States}}
 |-
-| 2014 || 9,190 || 7,660 || 12,800 || 3,120 || 6,690
+| 1935 || Research || Organ level effect (bone) || Harmful || {{w|Rodent}} ({{w|rat}}) || Study by {{w|Clive McCay}} and colleagues reports that calorie restriction results in extremely brittle femurs.<ref name=wwwd/> || {{w|United States}}
 |-
-| 2016 || 9,110 || 8,240 || 13,000 || 3,140 || 6,400
+| 1935 || Research || Longevity || Helpful || {{w|Rodent}} ({{w|rat}}) || {{w|Clive McCay}} and colleagues publish a landmark paper in the ''{{w|Journal of Nutrition}}'' entitled ''The effect of retarded growth upon the length of life span and upon the ultimate body size'' which provides the first systematic research evidence that calorie restriction prolongs life.<ref name="Simpson">{{cite journal |last1=Le Couteur |first1=David G |last2=Simpson |first2=Stephen J |title=90th Anniversary Commentary: Caloric Restriction Effects on Aging |journal=The Journal of Nutrition |date=1 October 2018 |volume=148 |issue=10 |pages=1656–1659 |doi=10.1093/jn/nxy146 |url=https://academic.oup.com/jn/article/148/10/1656/5114312?rss=1 |issn=0022-3166}}</ref><ref name="opiyu">{{cite journal |last1=McDonald |first1=Roger B. |last2=Ramsey |first2=Jon J. |title=Honoring Clive McCay and 75 Years of Calorie Restriction Research |journal=The Journal of Nutrition |date=2010 |volume=140 |issue=7 |pages=1205–1210 |doi=10.3945/jn.110.122804 |url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2884327/ |access-date=26 February 2021 |issn=0022-3166}}</ref>
 |-
-| 2017 || 9,590 || 8,870 || 13,500 || 3,880 || 6,910
+| 1939 || Research || Longevity || Neutral || N/A || C.M. McCay and colleagues publish a paper that defines for the first time the aging research value of the calorie restriction model, suggesting that calorie restriction may be a model for studying aging: “Retardation of growth by diets, complete except for calories, affords a means of producing very old animals for studying aging”.<ref>{{cite journal |last1=McCay |first1=C. M. |last2=Maynard |first2=L. A. |last3=Sperling |first3=G. |last4=Barnes |first4=LeRoy L. |title=THE JOURNAL OF NUTRITION: RETARDED GROWTH, LIFE SPAN, ULTIMATE BODY SIZE AND AGE CHANGES IN THE ALBINO RAT AFTER FEEDING DIETS RESTRICTED IN CALORIES |journal=Nutrition Reviews |date=27 April 2009 |volume=33 |issue=8 |pages=241–243 |doi=10.1111/j.1753-4887.1975.tb05227.x}}</ref> || {{w|United States}} ({{w|Cornell University}}, {{w|Ithaca, New York}})
 |-
-| 2018 || 9,840 || 9,280 || 14,200 || 3,570 || 7,220
+| 1942 || Research || Health ({{w|cancer}}) || Helpful || Human || Albert Tannenbaum writes: “It follows that the avoidance of overweight through restriction of food intake may aid in the prevention of human cancer or at least delay its onset”.<ref name="opiyu"/> ||
 |-
-| 2019 || 9,930 || 9,590 || 14,200 || 3,520 || 7,310
+| 1947 || Research || Lifespan and mortality || Helpful || {{w|Rodent}} ({{w|mouse}}) || Research by Ball and colleagues reports that lifelong dietary restriction dramatically extends the life span of mice (a maximum life span of 850 days vs. 550 days), whereas dietary restriction for the first 240 days has little effect.<ref name="Handbook of the"/> ||
 |-
-| 2020 || 12,000 || 10,100 || 13,400 || 3,760 || 7,420
+| 1948 || Background || || || || The current definition of the {{w|calorie}} is formally adopted as equivalent to approximately 4.2 {{w|joule}}s.<ref name="Calorie vvv"/> ||
 |-
-|}
+| 1951 || Research || Organ level effect ({{w|heart}}) || Helpful || {{w|Human}} || Study by Strom and Jensen recognizes beneficial effects of calorie restriction on heart function as a result of shortage of food during {{w|World War II}}.<ref>{{cite journal |last1=Strøm |first1=Axel |last2=Jensen |first2=R.Adelsten |last3=Oslo |first3=M.D. |last4=Oslo |first4=M.D. |title=MORTALITY FROM CIRCULATORY DISEASES IN NORWAY 1940-1945 |journal=The Lancet |date=January 1951 |volume=257 |issue=6647 |pages=126–129 |doi=10.1016/s0140-6736(51)91210-x}}</ref> || {{w|Norway}}
-[[File:Calorie restriction.png|thumb|center|700px]]
-=== Google Trends ===
-The chart below shows {{w|Google Trends}} data for Calorie restriction (search term), from January 2004 to June 2021, when the screenshot was taken. Interest is also ranked by country and displayed on world map <ref>{{cite web |title=Calorie restriction |url=https://trends.google.com/trends/explore?date=all&q=Calorie%20restriction |website=Google Trends |access-date=28 June 2021}}</ref>.
-[[File:Calorie restriction gt.png|thumb|center|600px]]
-=== Google Ngram Viewer ===
-The comparative chart below shows {{w|Google Ngram Viewer}} data for calorie restriction and caloric restriction, from 1900 to 2019.<ref>{{cite web |title=calorie restriction and caloric restriction |url=https://books.google.com/ngrams/graph?content=calorie+restriction%2C+caloric+restriction&year_start=1900&year_end=2019&corpus=26&smoothing=3&direct_url=t1%3B%2Ccalorie%20restriction%3B%2Cc0%3B.t1%3B%2Ccaloric%20restriction%3B%2Cc0#t1%3B%2Ccalorie%20restriction%3B%2Cc0%3B.t1%3B%2Ccaloric%20restriction%3B%2Cc0 |website=books.google.com |access-date=28 June 2021 |language=en}}</ref>
-[[File:Calorie restriction ngram.png|thumb|center|700px]]
-=== Wikipedia Views ===
-The chart below shows pageviews of the English Wikipedia article {{w|Calorie restriction}}, from July 2015 to May 2021.<ref>{{cite web |title=Calorie restriction |url=https://wikipediaviews.org/displayviewsformultiplemonths.php?page=Calorie+restriction&allmonths=allmonths-api&language=en&drilldown=all |website=wikipediaviews.org |access-date=28 June 2021}}</ref>
-[[File:Calorie restriction wv.png|thumb|center|550px]]
-==Full timeline==
-{| class="sortable wikitable"
-! Year !! Event type !! Calorie restriction effect type (when applicable) !! Effect direction (when applicable) !! Research subject species (when applicable) !! Details !! Location/researcher affiliation
 |-
-| 1819–1824 || Background || || || || The {{w|calorie}} is first introduced by French chemist {{w|Nicolas Clément}}, as a unit of {{w|heat}} energy, in lectures during these years.<ref name="Hargrove">{{cite journal |last1=Hargrove |first1=James L |title=Does the history of food energy units suggest a solution to "Calorie confusion"? |journal=Nutrition Journal |date=December 2007 |volume=6 |issue=1 |pages=44 |doi=10.1186/1475-2891-6-44}}</ref><ref name=Hist>{{cite journal|last=Hargrove|first=James L|title=Does the history of food energy units suggest a solution to "Calorie confusion"? |journal=Nutrition Journal |year=2007|volume=6|issue=44|pages=44|doi=10.1186/1475-2891-6-44 |pmid=18086303|pmc=2238749}}</ref> || {{w|France}}
+| 1951 || Research || Lifespan and mortality || Helpful || ''{{w|Tokophrya infusionum}}'' || Study by Maria A. Rudzinska reports that calorie restriction decreases the mortality rate in ''Tokophrya infusionum'' ({{w|protozoan}}).<ref>{{cite journal |last1=Rudzinska |first1=M. A. |title=The Influence of Amount of Food on the Reproduction Rate and Longevity of a Suctorian (Tokophrya infusionum) |journal=Science |date=5 January 1951 |volume=113 |issue=2923 |pages=10–11 |doi=10.1126/science.113.2923.10}}</ref> || {{w|United States}} ({{w|New York University}})
 |-
-| 1879 || Background || || || || French chemist {{w|Marcellin Berthelot}} distinguishes between gram-calorie (modern calorie) and kilogram-calorie (modern kilocalorie).<ref name="Hargrove"/> || {{w|France}}
+| 1960 || Research || Lifespan and mortality || Helpful || {{w|Rodent}} ({{w|rat}}) || Study by Benjamin N. Berg and Henry S. Simms published in the ''{{w|Journal of Nutrition}}'' proposes link between {{w|life extension}} and reduction in body fat content.<ref>{{cite journal |last1=Berg |first1=Benjamin N. |last2=Simms |first2=Henry S. |title=Nutrition and Longevity in the Rat |journal=The Journal of Nutrition |date=1 July 1960 |volume=71 |issue=3 |pages=255–263 |doi=10.1093/jn/71.3.255}}</ref><ref name="asqw">{{cite journal |last1=Masoro |first1=Edward J. |title=History of Caloric Restriction, Aging and Longevity |journal=Calorie Restriction, Aging and Longevity |date=2010 |pages=3–14 |doi=10.1007/978-90-481-8556-6_1#:~:text=1.1+introduction,retarded+growth+on+life+span |url=https://link.springer.com/chapter/10.1007/978-90-481-8556-6_1#:~:text=1.1%20Introduction,retarded%20growth%20on%20life%20span |access-date=26 February 2021 |publisher=Springer Netherlands |language=en}}</ref> || {{w|United States}}
 |-
-| 1887 || Background || || || || The use of the kilogram-calorie (kcal) for nutrition is introduced in the United States by American chemist {{w|Wilbur Olin Atwater}}, a professor at {{w|Wesleyan University}}.<ref name=Hist/> || {{w|United States}} ({{w|Wesleyan University}}, {{w|Connecticut}})
+| 1961 || Research || Lifespan and mortality || Helpful || {{w|Rodent}} ({{w|brown rat}}) || Study by M.H. Ross reports on calorie restriction decreasing the mortality rate in ''{{w|Rattus norvegicus}}'' (rat).<ref>{{cite journal |last1=Ross |first1=Morris H. |title=Length of Life and Nutrition in the Rat |journal=The Journal of Nutrition |date=1 October 1961 |volume=75 |issue=2 |pages=197–210 |doi=10.1093/jn/75.2.197}}</ref> || {{w|United States}} (Biochemical Research Foundation, {{w|Newark, Delaware}})
 |-
-| 1896 || Background || || || || The modern {{w|calorie}} (cal) is first recognized as a unit of the {{w|centimetre–gram–second system of units}} (cgs).<ref name="Hargrove"/> ||
+| 1963 || Research || Lifespan and mortality || Helpful || {{w|Fish}} || Study by Alex Comfort reports that retarding the growth of {{w|fish}} by restricting food increases their longevity.<ref>{{cite journal |last1=Comfort |first1=A. |title=Effect of Delayed and Resumed Growth on the Longevity of a Fish (Lebistes reticulatus, Peters) in Captivity |journal=Gerontology |date=1963 |volume=8 |issue=2-3 |pages=150–155 |doi=10.1159/000211216}}</ref> || {{w|United Kingdom}} ({{w|University College London}})
 |-
-| 1909 || Research || Health (cancer) || Helpful || {{w|Rat}} || Italian immunologist in Germany {{w|Carlo Moreschi}} finds that tumors transplanted into rats that were underfed did not grow as well as those transplanted into ''{{w|Ad libitum}}'' fed rats. This is the first hint that calorie restriction may have an effect on tumor progression.<ref name="Speakman"/> || {{w|Germany}}
+| 1965 || Research || Lifespan and mortality || Helpful || {{w|Rotifer}} (''{{w|Philodina acuticornis}}'')  || Study by D.D. Fanestil and C.H. Barrows Jr reports on calorie restriction decreasing the mortality rate in ''{{w|Philodina acuticornis}}'', a species of freshwater bdelloid rotifers.<ref>{{c  ite journal |last1=Dd |first1=Fanestil |last2=Ch |first2=Barrows |title=Aging in the rotifer |journal=Journal of gerontology |date=1965 Oct |url=https://pubmed.ncbi.nlm.nih.gov/5835014/ |language=en}}</ref> ||
 |-
-| 1914 || Research || Health (cancer) || Helpful || {{w|Rodent}} || American virologist {{w|Francis Peyton Rous}} reports that reducing food intake inhibits the occurrence of spontaneous cancers in rodents.<ref>{{cite book |last1=Everitt |first1=Arthur V. |last2=Rattan |first2=Suresh I. S. |last3=Couteur |first3=David G. |last4=Cabo |first4=Rafael de |title=Calorie Restriction, Aging and Longevity |publisher=Springer Science & Business Media |isbn=978-90-481-8556-6 |url=https://books.google.com.ar/books?id=zWgEkmHwjo8C&pg=PA4&lpg=PA4&dq=%22Calorie+restriction%22+%22in+1900..1930%22&source=bl&ots=vldtO4AGUn&sig=ACfU3U1uZ05sGxTWAJ6_oV4JjgEO_sxvJw&hl=en&sa=X&ved=2ahUKEwjo68y4r5XoAhVGHbkGHcQRD2EQ6AEwC3oECA0QAQ#v=onepage&q=%22Calorie%20restriction%22%20%22in%201900..1930%22&f=false |language=en}}</ref><ref>{{cite journal |last1=Rous |first1=Peyton |title=THE INFLUENCE OF DIET ON TRANSPLANTED AND SPONTANEOUS MOUSE TUMORS |journal=Journal of Experimental Medicine |date=1 November 1914 |volume=20 |issue=5 |pages=433–451 |doi=10.1084/jem.20.5.433}}</ref> || {{w|United States}}
+| 1973 || Research || Health ({{w|immune system}}) || Helpful || {{w|Rodent}} || Study by American pathologist {{w|Roy Walford}} et al. in rodents using intermitent fasting protocol to explore the humoral responses of subjects reports that after 1 year of restriction, {{w|Immunoglobulin M}} and {{w|Immunoglobulin G}} antibodies activity was augmented.<ref>{{cite journal |last1=Walford |first1=R.L. |last2=Liu |first2=R.K. |last3=Gerbase-Delima |first3=M. |last4=Mathies |first4=M. |last5=Smith |first5=G.S. |title=Longterm dietary restriction and immune function in mice: Response to sheep red blood cells and to mitogenic agents |journal=Mechanisms of Ageing and Development |date=January 1973 |volume=2 |pages=447–454 |doi=10.1016/0047-6374(73)90035-3}}</ref> Being among the first to study the effects of calorie restriction on immune function in rodents, Walford would become a strong advocate for the use of calorie restriction in humans.<ref name="Speakman"/> || {{w|United States}} ([[w:David Geffen School of Medicine at UCLA|UCLA School of Medicine]], {{w|Los Angeles}})
 |-
-| 1917 || Research || Lifespan and mortality || Helpful || || American biochemists [[w:Thomas Burr Osborne (chemist)|Thomas Osborne]] and {{w|Lafayette Mendel}} publish the first scientific study showing that restricting food extends life.<ref name="Handbook of the">{{cite book |title=Handbook of the biology of aging |date=2006 |publisher=Elsevier Academic Press |location=Amsterdam |isbn=9780120883875 |edition=6th}}</ref> || {{w|United States}} ({{w|Yale University}}, {{w|New Haven, Connecticut}})
+| 1977 || Research || Metabolic effect || Helpful || N/A || American biologist George A. Sacher proposes that calorie restriction retards aging by decreasing the intensity of energy metabolism.<ref name="Subfield His"/> || {{w|United States}} ({{w|Argonne National Laboratory}})
 |-
-| 1918 || Literature || Weight loss || Helpful || {{w|Human}} || American doctor {{w|Lulu Hunt Peters}} publishes ''Diet & Health: With Key to the Calories'', which is aimed at women and  presents the concept of calorie reduction as the best form of weight loss and watching weight.<ref name=Lit>{{cite web |first=Emily |last=Temple |url=https://lithub.com/some-hilarious-illustrations-from-americas-first-bestselling-diet-book/ |title=Some Hilarious Illustrations from America’s First Bestselling Diet Book  |website=LitHub |date=January 15, 2019 }}</ref>
+| 1977 || Research || Lifespan and mortality || Helpful || {{w|Nematode}} (''{{w|Caenorhabditis elegans}}'') || Study by M.R. Klass reports on calorie restriction decreasing the mortality rate in ''{{w|C. elegans}}''.<ref>{{cite journal |last1=Klass |first1=Michael R. |title=Aging in the nematode Caenorhabditis elegans: Major biological and environmental factors influencing life span |journal=Mechanisms of Ageing and Development |date=January 1977 |volume=6 |pages=413–429 |doi=10.1016/0047-6374(77)90043-4}}</ref> || {{w|United States}} ({{w|University of Colorado Boulder}})
 |-
-| 1920 || Research || Longevity || Harmful || || In opposition to 1917 report by Osborne and Mendel, T. Robertson and L.A. Ray publish scientific study concluding that restricting food shortens life.<ref>{{cite journal |last1=Robertson |first1=T.Brailsford |last2=Ray |first2=L.A. |title=EXPERIMENTAL STUDIES ON GROWTH |journal=Journal of Biological Chemistry |date=November 1920 |volume=44 |issue=2 |pages=439–453 |doi=10.1016/S0021-9258(18)86250-0}}</ref><ref name="Handbook of the"/> || {{w|Australia}} ({{w|University of Adelaide}}), {{w|Canada}} ({{w|University of Toronto}})
+| 1978 || Notable case || Mortality || Harmful || {{w|Human}} || In this year, 58 people die in the United States after following very-low-calorie liquid protein diets.<ref name="Zoumbaris2014">{{cite book |last1=Zoumbaris |first1=Sharon K. |last2=Bijlefeld |first2=Marjolijn |title=Encyclopedia of diet fads : understanding science and society |publisher=Greenwood |date=25 November 2014 |isbn=9781610697606 |edition=2nd |url=https://books.google.com/books?id=4jq2BQAAQBAJ |type=Encyclopaedia}}</ref> || {{w|United States}}
 |-
-| 1925 || Background || || || || The {{w|calorie}} starts being defined in terms of the {{w|joule}}.<ref name="Calorie vvv">{{cite web |title=Calorie {{!}} unit of measurement |url=https://www.britannica.com/science/calorie |website=Encyclopedia Britannica |access-date=7 July 2021 |language=en}}</ref> ||
+| 1980 || Research || Organ level effect ({{w|white adipose tissue}}) || Helpful || {{w|Rodent}} ({{w|rat}}) || Study by Helen A. Bertrand et al. in rats reports that, under calorie restriction, the loss of {{w|white adipose tissue}} is disproportionately large.<ref>{{cite journal |last1=Bertrand |first1=H. A. |last2=Lynd |first2=F. T. |last3=Masoro |first3=E. J. |last4=Yu |first4=B. P. |title=Changes in Adipose Mass and Cellularity Through the Adult Life of Rats Fed Ad Libitum or a Life-Prolonging Restricted Diet |journal=Journal of Gerontology |date=1980-11-01 |volume=35 |issue=6 |pages=827–835 |doi=10.1093/geronj/35.6.827}}</ref> || {{w|United States}}
 |-
-| 1935 || Research || Longevity || Helpful || {{w|Rat}} || American biochemist {{w|Clive McCay}} and his colleagues publish a seminal paper, which shows that slowing the post-weaning growth of rats by markedly restricting their food intake significantly increases their longevity.<ref name="asqw"/> This is the first widely known scientific publication on the impact of dietary restriction on life expectancy.<ref name="Zainabadi">{{cite journal | vauthors = Zainabadi K | title = A brief history of modern aging research | journal = Experimental Gerontology | volume = 104 | pages = 35–42 | date = April 2018 | pmid = 29355705 | doi = 10.1016/j.exger.2018.01.018 | s2cid = 3972313 }}</ref><ref>{{cite journal| vauthors = McCay CM, Crowell M |date=October 1934 |title=Prolonging the Life Span |url=https://www.jstor.org/stable/15813 |journal=[[The Scientific Monthly]] |volume=39 |issue=5 |pages=405–414 |doi= |jstor=15813 |pmc= |pmid= |bibcode=1934SciMo..39..405M }}</ref><ref>{{cite journal| vauthors = McCay CM, Crowell MF, Maynard LA |date=1 July 1935 |title=The Effect of Retarded Growth Upon the Length of Life Span and Upon the Ultimate Body Size |url=http://www.wealthandhealth.ltd.uk/over100/C.%20M.%20McCAY%201935.pdf |journal=[[The Journal of Nutrition]] |volume=10 |issue=1 |pages=63–79 |doi=10.1093/jn/10.1.63 |pmc= |pmid=}}</ref> || {{w|United States}}
+| 1980 || Research || Lifespan and mortality || Helpful || {{w|Rodent}} ''({{w|Mus musculus}})''  || Study by K.E. Cheney and colleagues reports on calorie restriction decreasing the mortality rate in [[w:House mouse|house mice]].<ref>{{cite journal |last1=Cheney |first1=K.E. |last2=Liu |first2=R.K. |last3=Smith |first3=G.S. |last4=Leung |first4=R.E. |last5=Mickey |first5=M.R. |last6=Walford |first6=R.L. |title=Survival and disease patterns in C57BL/6J mice subjected to undernutrition |journal=Experimental Gerontology |date=January 1980 |volume=15 |issue=4 |pages=237–258 |doi=10.1016/0531-5565(80)90029-7}}</ref> || {{w|United States}} ({{w|University of California, Los Angeles}})
 |-
-| 1935 || Research || Organ level effect (bone) || Harmful || || Study by {{w|Clive McCay}} and colleagues reports that calorie restriction results in extremely brittle femurs.<ref>{{cite journal |last1=McCay |first1=C. M. |last2=Crowell |first2=Mary F. |last3=Maynard |first3=L. A. |title=The Effect of Retarded Growth Upon the Length of Life Span and Upon the Ultimate Body Size |journal=The Journal of Nutrition |date=1935-07-01 |volume=10 |issue=1 |pages=63–79 |doi=10.1093/jn/10.1.63}}</ref> || {{w|United States}}
+| 1982 || Research || Lifespan and mortality || Helpful || {{w|Rodent}} ({{w|mouse}}) || Study by Richard Weindruch and {{w|Roy Walford}} in 12- to 13-month-old mice on food restriction by using nutrient-enriched diets in accordance with the concept of "undernutrition without malnutrition" results in the mice on the restricted diet averaging 10 to 20 percent increases in mean and maximum survival times compared to the control mice.<ref name="Speakman">{{cite journal |last1=Speakman |first1=John R. |last2=Mitchell |first2=Sharon E. |title=Caloric restriction |journal=Molecular Aspects of Medicine |date=June 2011 |volume=32 |issue=3 |pages=159–221 |doi=10.1016/j.mam.2011.07.001}}</ref><ref>{{cite journal |last1=Weindruch |first1=R |last2=Walford |first2=R. |title=Dietary restriction in mice beginning at 1 year of age: effect on life-span and spontaneous cancer incidence |journal=Science |date=1982-03-12 |volume=215 |issue=4538 |pages=1415–1418 |doi=10.1126/science.7063854}}</ref> || {{w|United States}}
 |-
-| 1935 || Research || Longevity || Helpful || || {{w|Clive McCay}} and colleagues publish a landmark paper in the ''{{w|Journal of Nutrition}}'' entitled ''The effect of retarded growth upon the length of life span and upon the ultimate body size'' which provides the first systematic research evidence that calorie restriction prolongs life.<ref name="Simpson">{{cite journal |last1=Le Couteur |first1=David G |last2=Simpson |first2=Stephen J |title=90th Anniversary Commentary: Caloric Restriction Effects on Aging |journal=The Journal of Nutrition |date=1 October 2018 |volume=148 |issue=10 |pages=1656–1659 |doi=10.1093/jn/nxy146 |url=https://academic.oup.com/jn/article/148/10/1656/5114312?rss=1 |issn=0022-3166}}</ref><ref name="opiyu">{{cite journal |last1=McDonald |first1=Roger B. |last2=Ramsey |first2=Jon J. |title=Honoring Clive McCay and 75 Years of Calorie Restriction Research |journal=The Journal of Nutrition |date=2010 |volume=140 |issue=7 |pages=1205–1210 |doi=10.3945/jn.110.122804 |url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2884327/ |access-date=26 February 2021 |issn=0022-3166}}</ref>
+| 1984 || Policy || Illness || Harmful || Human || The United States {{w|FDA}} starts requiring that {{w|very-low-calorie diet}}s providing fewer than 400 calories a day to carry a warning that they can cause serious illness and need to be followed under medical supervision.<ref name="Zoumbaris2014" /> || {{w|United States}}
 |-
-| 1939 || Research || Longevity || Neutral || || C.M. McCay and colleagues publish a paper that defines for the first time the aging research value of the calorie restriction model, suggesting that calorie restriction may be a model for studying aging: “Retardation of growth by diets, complete except for calories, affords a means of producing very old animals for studying aging”.<ref>{{cite journal |last1=McCay |first1=C. M. |last2=Maynard |first2=L. A. |last3=Sperling |first3=G. |last4=Barnes |first4=LeRoy L. |title=THE JOURNAL OF NUTRITION: RETARDED GROWTH, LIFE SPAN, ULTIMATE BODY SIZE AND AGE CHANGES IN THE ALBINO RAT AFTER FEEDING DIETS RESTRICTED IN CALORIES |journal=Nutrition Reviews |date=27 April 2009 |volume=33 |issue=8 |pages=241–243 |doi=10.1111/j.1753-4887.1975.tb05227.x}}</ref> || {{w|United States}} ({{w|Cornell University}}, {{w|Ithaca, New York}})
+| 1984 || Literature || Lifespan and mortality || Helpful || Human || Roy Walford publishes ''Maximum Life Span'' a book on lifespan determination advocating calorie restriction.<ref name="Speakman"/>
 |-
-| 1942 || Research || Health ({{w|cancer}}) || Helpful || || Albert Tannenbaum writes: “It follows that the avoidance of overweight through restriction of food intake may aid in the prevention of human cancer or at least delay its onset”.<ref name="opiyu"/> ||
+| 1984 || Research || Organ level effect (bone) || Helpful || Rodent ({{w|rat}}) || Research by Kalu et al. in rats concludes that calorie restriction completely prevents the senile bone loss recorded in ''{{w|ad libitum}}'' rats with femur strength to body weight ratios greater than in ''{{w|ad libitum}}''.<ref>{{cite journal |last1=Kalu |first1=Dike N. |last2=Hardin |first2=Robert R. |last3=Cockerham |first3=Richard |last4=Yu |first4=Byung P. |last5=Norling |first5=Barry K. |last6=Egan |first6=John W. |title=Lifelong food restriction prevents senile osteopenia and hyperparathyroidism in F344 rats |journal=Mechanisms of Ageing and Development |date=July 1984 |volume=26 |issue=1 |pages=103–112 |doi=10.1016/0047-6374(84)90169-6}}</ref> || {{w|United States}} ({{w|University of Texas Health Science Center at San Antonio}})
 |-
-| 1947 || Research || Lifespan and mortality || Helpful || {{w|Mouse}} || Research by Ball and colleagues reports that lifelong dietary restriction dramatically extends the life span of mice (a maximum life span of 850 days vs. 550 days), whereas dietary restriction for the first 240 days has little effect.<ref name="Handbook of the"/> ||
+| 1986 || Literature || Lifespan and mortality || Helpful || Human || Richard Weindruch and {{w|Roy Walford}} publish ''The Retardation of Aging and Disease by Dietary Restriction'', an influential and comprehensive encyclopedia of calorie restriction studies that would encourage many scientists to become interested in, and to investigate, calorie restriction and its impact on aging.<ref name="Simpson"/> || {{w|United States}}
 |-
-| 1948 || Background || || || || The current definition of the {{w|calorie}} is formally adopted as equivalent to approximately 4.2 {{w|joule}}s.<ref name="Calorie vvv"/> ||
+| 1986 || Literature || Lifespan and mortality || Helpful || Human || {{w|Roy Walford}} publishes ''The 120-Year Diet: How to Double Your Vital Years'', advocating the use of calorie restriction to increase human longevity.<ref name="Speakman"/><ref>{{cite book |last1=Leary |first1=Timothy |title=Alternatives to Involuntary Death |date=1 April 2009 |publisher=Ronin Publishing |isbn=978-1-57951-096-1 |url=https://books.google.com.ar/books?id=h6LoBAAAQBAJ&pg=PA57&dq=The+120-Year+Diet:+How+to+Double+Your+Vital+Years&hl=en&sa=X&ved=2ahUKEwjFhtjt4MnxAhVUHbkGHQP0CkUQ6AEwCHoECAsQAg#v=onepage&q=The%20120-Year%20Diet%3A%20How%20to%20Double%20Your%20Vital%20Years&f=false |language=en}}</ref> || {{w|United States}}
 |-
-| 1951 || Research || Organ level effect ({{w|heart}}) || Helpful || {{w|Human}} || Study by Strom and Jensen recognizes beneficial effects of calorie restriction on heart function as a result of shortage of food during {{w|World War II}}.<ref>{{cite journal |last1=Strøm |first1=Axel |last2=Jensen |first2=R.Adelsten |last3=Oslo |first3=M.D. |last4=Oslo |first4=M.D. |title=MORTALITY FROM CIRCULATORY DISEASES IN NORWAY 1940-1945 |journal=The Lancet |date=January 1951 |volume=257 |issue=6647 |pages=126–129 |doi=10.1016/s0140-6736(51)91210-x}}</ref> || {{w|Norway}}
+| 1987 || Research || Behavior ({{w|physical activity}}) || Helpful || {{w|Rodent}} || Study by D E Harrison and J R Archer reports that the response shown by many rodents to calorie restriction is actually to increase levels of activity.<ref>{{cite journal |last1=Harrison |first1=D. E. |last2=Archer |first2=J. R. |title=Genetic Differences in Effects of Food Restriction on Aging in Mice |journal=The Journal of Nutrition |date=1987-02-01 |volume=117 |issue=2 |pages=376–382 |doi=10.1093/jn/117.2.376}}</ref><ref name="Speakman"/>
 |-
-| 1951 || Research || Lifespan and mortality || Helpful || ''{{w|Tokophrya infusionum}}'' || Study by Maria A. Rudzinska reports that calorie restriction decreases the mortality rate in ''Tokophrya infusionum'' ({{w|protozoan}}).<ref>{{cite journal |last1=Rudzinska |first1=M. A. |title=The Influence of Amount of Food on the Reproduction Rate and Longevity of a Suctorian (Tokophrya infusionum) |journal=Science |date=5 January 1951 |volume=113 |issue=2923 |pages=10–11 |doi=10.1126/science.113.2923.10}}</ref> || {{w|United States}} ({{w|New York University}})
+| 1988 || Literature || Lifespan and mortality || Helpful || Human || {{w|Roy Walford}} and Richard Weindruch publish ''The Retardation of Aging and Disease by Dietary Restriction''.<ref name="Speakman"/> || {{w|United States}}
 |-
-| 1960 || Research || Lifespan and mortality || Helpful || || Study by Benjamin N. Berg and Henry S. Simms published in the ''{{w|Journal of Nutrition}}'' proposes link between {{w|life extension}} and reduction in body fat content.<ref>{{cite journal |last1=Berg |first1=Benjamin N. |last2=Simms |first2=Henry S. |title=Nutrition and Longevity in the Rat |journal=The Journal of Nutrition |date=1 July 1960 |volume=71 |issue=3 |pages=255–263 |doi=10.1093/jn/71.3.255}}</ref><ref name="asqw">{{cite journal |last1=Masoro |first1=Edward J. |title=History of Caloric Restriction, Aging and Longevity |journal=Calorie Restriction, Aging and Longevity |date=2010 |pages=3–14 |doi=10.1007/978-90-481-8556-6_1#:~:text=1.1+introduction,retarded+growth+on+life+span |url=https://link.springer.com/chapter/10.1007/978-90-481-8556-6_1#:~:text=1.1%20Introduction,retarded%20growth%20on%20life%20span |access-date=26 February 2021 |publisher=Springer Netherlands |language=en}}</ref> || {{w|United States}}
+| 1991–1993 || Diet introduction || || Helpful || Human || {{w|Roy Walford}}'s compiled data during his participation in {{w|Biosphere 2}} is used to develop the {{w|CRON-diet}}, jointly with Lisa Walford, and {{w|Brian M. Delaney}}. IT consists in eating a diet low in fat and in calories but "nutrient-dense".<ref>{{Cite journal | pmid = 1454844 | year = 1992 | last= Walford | first = R. L. | title = The calorically restricted low-fat nutrient-dense diet in Biosphere 2 significantly lowers blood glucose, total leukocyte count, cholesterol, and blood pressure in humans| journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 89 | issue = 23 | pages = 11533–11537 | last2 = Harris | first2 = S. B. | last3 = Gunion | first3 = M. W. | pmc = 50586  | doi=10.1073/pnas.89.23.11533}}</ref><ref name="Nagourney NYT 2000">{{cite news |last1=Nagourney |first1=Eric |title=Ups and Downs for Diet Guinea Pigs |url=https://www.nytimes.com/2000/09/26/science/ups-and-downs-for-diet-guinea-pigs.html |work={{w|The New York Times}} |date=26 September 2000}}</ref> || {{w|United States}}
 |-
-| 1961 || Research || Lifespan and mortality || Helpful || {{w|Brown rat}} || Study by M.H. Ross reports on calorie restriction decreasing the mortality rate in ''{{w|Rattus norvegicus}}'' (rat).<ref>{{cite journal |last1=Ross |first1=Morris H. |title=Length of Life and Nutrition in the Rat |journal=The Journal of Nutrition |date=1 October 1961 |volume=75 |issue=2 |pages=197–210 |doi=10.1093/jn/75.2.197}}</ref> || {{w|United States}} (Biochemical Research Foundation, {{w|Newark, Delaware}})
+| 1993 || Research || Organ level effect (liver) || N/A || {{w|Rodent}} ({{w|rat}}) || Research by Alterman et al. in rats shows that calorie restriction has profound effects on the hepatic microsomal levels and activities of {{w|cytochrome P-450s}}, a [[w:Protein superfamily|superfamily]] of {{w|enzyme}}s containing {{w|heme}} as a [[w:cofactor (biochemistry)|cofactor]] that functions as {{w|monooxygenase}}s.<ref>{{cite journal |last1=Alterman |first1=Michail |last2=Carvan |first2=Michael |last3=Srivastava |first3=Vinod |last4=Leakey |first4=Julian |last5=Hart |first5=Ron |last6=Busbee |first6=David |title=Effects of aging and long-term caloric restriction on hepatic microsomal monooxygenases in female fischer 344 rats: Alterations in basal cytochrome P-450 catalytic activities |journal=AGE |date=January 1993 |volume=16 |issue=1 |pages=1–8 |doi=10.1007/BF02436124}}</ref> || {{w|United States}} ({{w|Texas A&M University}})
 |-
-| 1963 || Research || Lifespan and mortality || Helpful || {{w|Fish}} || Study by Alex Comfort reports that retarding the growth of {{w|fish}} by restricting food increases their longevity.<ref>{{cite journal |last1=Comfort |first1=A. |title=Effect of Delayed and Resumed Growth on the Longevity of a Fish (Lebistes reticulatus, Peters) in Captivity |journal=Gerontology |date=1963 |volume=8 |issue=2-3 |pages=150–155 |doi=10.1159/000211216}}</ref> || {{w|United Kingdom}} ({{w|University College London}})
+| 1994 || Organization || Lifespan and mortality || Helpful || Human || The {{w|Calorie Restriction Society}} is founded. This organization sponsors conferences, funds anti-aging research, and offers practical guidance to its members.<ref>{{cite web |title=Embryonic CR Society |url=https://www.crsociety.org/about/history/ |website=crsociety.org |access-date=5 May 2021}}</ref> || {{w|United States}}
 |-
-| 1965 || Research || Lifespan and mortality || Helpful || ''{{w|Philodina acuticornis}}'' ({{w|rotifera}}) || Study by D.D. Fanestil and C.H. Barrows Jr reports on calorie restriction decreasing the mortality rate in ''{{w|Philodina acuticornis}}'', a species of freshwater bdelloid rotifers.<ref>{{c  ite journal |last1=Dd |first1=Fanestil |last2=Ch |first2=Barrows |title=Aging in the rotifer |journal=Journal of gerontology |date=1965 Oct |url=https://pubmed.ncbi.nlm.nih.gov/5835014/ |language=en}}</ref> ||
+| 1994 || Research || Health (cancer) || Helpful || {{w|Rodent}} ({{w|mouse}}) || Study by Peter P. Fu and colleagues shows that caloric restriction profoundly inhibits liver-tumor formation after initiation by 6-nitrochrysene in male-mice.<ref>{{cite journal |last1=Fu |first1=Peter P. |last2=Dooley |first2=Kenneth L. |last3=Von Tungeln |first3=Linda S. |last4=Bucci |first4=Thomas |last5=Hart |first5=Ronald W. |last6=Kadlubar |first6=Fred F. |title=Caloric restriction profoundly inhibits liver tumor formation after initiation by 6-nitrochrysene in male mice |journal=Carcinogenesis |date=1994 |volume=15 |issue=2 |pages=159–161 |doi=10.1093/carcin/15.2.159}}</ref><ref name="Speakman"/> || {{w|United States}} ({{w|National Center for Toxicological Research}}, {{w|Arkansas}})
 |-
-| 1973 || Research || Health ({{w|immune system}}) || Helpful || {{w|Rodent}} || Study by American pathologist {{w|Roy Walford}} et al. in rodents using intermitent fasting protocol to explore the humoral responses of subjects reports that after 1 year of restriction, {{w|Immunoglobulin M}} and {{w|Immunoglobulin G}} antibodies activity was augmented.<ref>{{cite journal |last1=Walford |first1=R.L. |last2=Liu |first2=R.K. |last3=Gerbase-Delima |first3=M. |last4=Mathies |first4=M. |last5=Smith |first5=G.S. |title=Longterm dietary restriction and immune function in mice: Response to sheep red blood cells and to mitogenic agents |journal=Mechanisms of Ageing and Development |date=January 1973 |volume=2 |pages=447–454 |doi=10.1016/0047-6374(73)90035-3}}</ref> Being among the first to study the effects of calorie restriction on immune function in rodents, Walford would become a strong advocate for the use of calorie restriction in humans.<ref name="Speakman"/> || {{w|United States}} ([[w:David Geffen School of Medicine at UCLA|UCLA School of Medicine]], {{w|Los Angeles}})
+| 1994 || Research || Metabolic effect ({{w|oxidative stress}}) || Helpful || {{w|Rodent}} ({{w|mouse}}) || Study by R.S. Sohal and colleagues in mice reports that isolated {{w|mitochondria}} from subjects under calorie restriction show reductions in {{w|superoxide}} radical production.<ref>{{cite journal |last1=Sohal |first1=Rajindar S. |last2=Ku |first2=Hung-Hai |last3=Agarwal |first3=Sanjiv |last4=Forster |first4=Michael J. |last5=Lal |first5=Harbans |title=Oxidative damage, mitochondrial oxidant generation and antioxidant defenses during aging and in response to food restriction in the mouse |journal=Mechanisms of Ageing and Development |date=May 1994 |volume=74 |issue=1-2 |pages=121–133 |doi=10.1016/0047-6374(94)90104-x}}</ref> || {{w|Unted States}} ({{w|Southern Methodist University}}, {{w|Dallas}})
 |-
-| 1977 || Research || Metabolic effect || Helpful || || American biologist George A. Sacher proposes that calorie restriction retards aging by decreasing the intensity of energy metabolism.<ref name="Subfield His"/> || {{w|United States}} ({{w|Argonne National Laboratory}})
+| 1995 || Research || Behavior (cognitive effect) || Neutral || N/A || Study by M.W. Green et al. concludes that short-term food deprivation has little or no detrimental effect on cognitive function, also indicating that "deficits in cognitive function found to be associated with spontaneous dieting are unlikely to be due primarily to any direct physiological or nutritional effects of food deprivation".<ref>{{cite journal |last1=Green |first1=Michael W. |last2=Elliman |first2=Nicola A. |last3=Rogers |first3=Peter J. |title=Lack of effect of short-term fasting on cognitive function |journal=Journal of Psychiatric Research |date=May 1995 |volume=29 |issue=3 |pages=245–253 |doi=10.1016/0022-3956(95)00009-t}}</ref> || {{w|United Kingdom}} (Institute of Food Research, {{w|Reading, Berkshire}})
 |-
-| 1977 || Research || Lifespan and mortality || || || Study by M.R. Klass reports on calorie restriction decreasing the mortality rate in ''{{w|Caenorhabditis elegans}}'' ({{w|nematode}}).<ref>{{cite journal |last1=Klass |first1=Michael R. |title=Aging in the nematode Caenorhabditis elegans: Major biological and environmental factors influencing life span |journal=Mechanisms of Ageing and Development |date=January 1977 |volume=6 |pages=413–429 |doi=10.1016/0047-6374(77)90043-4}}</ref> || {{w|United States}} ({{w|University of Colorado Boulder}})
+| 1995 || Literature || Longevity || Helpful || Human || {{w|Roy Walford}} publishes ''The Anti-Aging Plan'', which promotes calorie restriction in humans.<ref name="Speakman"/>
 |-
-| 1978 || Notable case || Mortality || || || In this year, 58 people die in the United States after following very-low-calorie liquid protein diets.<ref name="Zoumbaris2014">{{cite book |last1=Zoumbaris |first1=Sharon K. |last2=Bijlefeld |first2=Marjolijn |title=Encyclopedia of diet fads : understanding science and society |publisher=Greenwood |date=25 November 2014 |isbn=9781610697606 |edition=2nd |url=https://books.google.com/books?id=4jq2BQAAQBAJ |type=Encyclopaedia}}</ref> || {{w|United States}}
+| 1995 || Research || Endocrine effect (leptin and other adipokines) || Harmful || {{w|Rodent}} ({{w|mouse}}) || Study by Robert C. Frederich and colleagues in mice shows that the loss of body fat during calorie restriction results in profound reductions in circulating levels of several {{w|adipokine}}s, including {{w|leptin}}.<ref>{{cite journal |last1=Frederich |first1=Robert C. |last2=Hamann |first2=Andreas |last3=Anderson |first3=Stephen |last4=Löllmann |first4=Bettina |last5=Lowell |first5=Bradford B. |last6=Flier |first6=Jeffrey S. |title=Leptin levels reflect body lipid content in mice: Evidence for diet-induced resistance to leptin action |journal=Nature Medicine |date=December 1995 |volume=1 |issue=12 |pages=1311–1314 |doi=10.1038/nm1295-1311}}</ref> || {{w|United States}} (Beth Israel Hospital, {{w|Boston}}, {{w|Massachusetts}})
 |-
-| 1980 || Research || Organ level effect ({{w|white adipose tissue}}) || || || Study by Helen A. Bertrand et al. in rats reports that, under calorie restriction, the loss of {{w|white adipose tissue}} is disproportionately large.<ref>{{cite journal |last1=Bertrand |first1=H. A. |last2=Lynd |first2=F. T. |last3=Masoro |first3=E. J. |last4=Yu |first4=B. P. |title=Changes in Adipose Mass and Cellularity Through the Adult Life of Rats Fed Ad Libitum or a Life-Prolonging Restricted Diet |journal=Journal of Gerontology |date=1980-11-01 |volume=35 |issue=6 |pages=827–835 |doi=10.1093/geronj/35.6.827}}</ref> || {{w|United States}}
+| 1996 || Research || Metabolic effect ({{w|oxidative stress}}) || Helpful || {{w|Rodent}} || Study by B.P. Yu in mice concludes that calorie restriction in subjects reduces oxidative stress.<ref>{{cite journal |last1=Yu |first1=Byung Pal |title=Aging and oxidative stress: Modulation by dietary restriction |journal=Free Radical Biology and Medicine |date=January 1996 |volume=21 |issue=5 |pages=651–668 |doi=10.1016/0891-5849(96)00162-1}}</ref> || {{w|United States}} (University of Texas Health Science Center, San Antonio)
 |-
-| 1980 || Research || Lifespan and mortality || || || Study by K.E. Cheney and colleagues reports on calorie restriction decreasing the mortality rate in ''{{w|Mus musculus}}'' (mouse).<ref>{{cite journal |last1=Cheney |first1=K.E. |last2=Liu |first2=R.K. |last3=Smith |first3=G.S. |last4=Leung |first4=R.E. |last5=Mickey |first5=M.R. |last6=Walford |first6=R.L. |title=Survival and disease patterns in C57BL/6J mice subjected to undernutrition |journal=Experimental Gerontology |date=January 1980 |volume=15 |issue=4 |pages=237–258 |doi=10.1016/0531-5565(80)90029-7}}</ref> || {{w|United States}} ({{w|University of California, Los Angeles}})
+| 1997 || Research || Health (cancer) || Helpful || {{w|Rodent}} || Study by Hart and Turturro in rodents reports that calorie restriction in subjects reduces the susceptibility to cancer.<ref>{{cite journal |last1=Hart |first1=R W |last2=Turturro |first2=A |title=Dietary restrictions and cancer. |journal=Environmental Health Perspectives |date=June 1997 |volume=105 |issue=suppl 4 |pages=989–992 |doi=10.1289/ehp.97105s4989}}</ref> || {{w|United States}} ({{w|National Center for Toxicological Research}}, [[w:Jefferson, Jefferson County, Arkansas|Jefferson]], {{w|Arkansas}})
 |-
-| 1982 || Research || Lifespan and mortality || || || Study by Richard Weindruch and {{w|Roy Walford}} in 12- to 13-month-old mice on food restriction by using nutrient-enriched diets in accordance with the concept of "undernutrition without malnutrition" results in the mice on the restricted diet averaging 10 to 20 percent increases in mean and maximum survival times compared to the control mice.<ref name="Speakman">{{cite journal |last1=Speakman |first1=John R. |last2=Mitchell |first2=Sharon E. |title=Caloric restriction |journal=Molecular Aspects of Medicine |date=June 2011 |volume=32 |issue=3 |pages=159–221 |doi=10.1016/j.mam.2011.07.001}}</ref><ref>{{cite journal |last1=Weindruch |first1=R |last2=Walford |first2=R. |title=Dietary restriction in mice beginning at 1 year of age: effect on life-span and spontaneous cancer incidence |journal=Science |date=1982-03-12 |volume=215 |issue=4538 |pages=1415–1418 |doi=10.1126/science.7063854}}</ref> ||
+| 1997 || Research || Organ level effect (alimentary tract) || Helpful || {{w|Rodent}} ({{w|mouse}}) || Study by Casirola et al. in mice reports that intestinal nutrient uptake in calorie restriction animals is significantly higher for D-sugars, L amino acids and L-glucose than in same-age ''{{w|ad libitum}}'' animals.<ref>{{cite journal |last1=Casirola |first1=D. M. |last2=Lan |first2=Y. |last3=Ferraris |first3=R. P. |title=Effects of Changes in Calorie Intake on Intestinal Nutrient Uptake and Transporter mRNA Levels in Aged Mice |journal=The Journals of Gerontology Series A: Biological Sciences and Medical Sciences |date=1997-11-01 |volume=52A |issue=6 |pages=B300–B310 |doi=10.1093/gerona/52a.6.b300}}</ref> || {{w|United States}} ({{w|University of Medicine and Dentistry of New Jersey}})
 |-
-| 1984 || Policy || Illness || || || The United States {{w|FDA}} starts requiring that {{w|very-low-calorie diet}}s providing fewer than 400 calories a day to carry a warning that they can cause serious illness and need to be followed under medical supervision.<ref name="Zoumbaris2014" /> || {{w|United States}}
+| 1997 || Research || Organ level effect (muscle) || Helpful || {{w|Rodent}} ({{w|mouse}}) || Study by Aspnes et al. in mice reports that calorie restriction has a protective effect against sarcopenic muscle loss in subjects.<ref>{{cite journal |last1=Aspnes |first1=Lauren E. |last2=Lee |first2=Connie M. |last3=Weindruch |first3=Richard |last4=Chung |first4=Susan S. |last5=Roecker |first5=Ellen B. |last6=Aiken |first6=Judd M. |title=Caloric restriction reduces fiber loss and mitochondrial abnormalities in aged rat muscle |journal=The FASEB Journal |date=June 1997 |volume=11 |issue=7 |pages=573–581 |doi=10.1096/fasebj.11.7.9212081}}</ref> || {{w|United States}} ({{w|University of Wisconsin–Madison}})
 |-
-| 1984 || Literature || Lifespan and mortality || || || Roy Walford publishes ''Maximum Life Span'' a bon lifespan determination advocating calorie restriction.<ref name="Speakman"/>
+| 1998 || Research || Health (cancer) || Helpful || {{w|Rodent}} ({{w|rat}}) || Study by T.J. Spady et al. shows that dietary energy restriction abolishes development of prolactin-producing pituitary tumors in rats treated with 17 beta-estradiol.<ref>{{cite journal |last1=Spady |first1=Thomas J. |last2=Lemus-Wilson |first2=Athena M. |last3=Pennington |first3=Karen L. |last4=Blackwood |first4=Darcy J. |last5=Paschall |first5=Tanya M. |last6=Birt |first6=Diane F. |last7=McComb |first7=Rodney D. |last8=Shull |first8=James D. |title=Dietary energy restriction abolishes development of prolactin-producing pituitary tumors in Fischer 344 rats treated with 17-βestradiol |journal=Molecular Carcinogenesis |date=1998 |volume=23 |issue=2 |pages=86–95 |doi=10.1002/(sici)1098-2744(199810)23:2<86::aid-mc5>3.0.co;2-5}}</ref> || {{w|United States}} ({{w|University of Nebraska Medical Center}}, {{w|Omaha}})
 |-
-| 1984 || Research || Organ level effect (bone) || || || Research by Kalu et al. in rats concludes that calorie restriction completely prevents the senile bone loss recorded in ''{{w|ad libitum}}'' rats with femur strength to body weight ratios greater than in ''{{w|ad libitum}}''.<ref>{{cite journal |last1=Kalu |first1=Dike N. |last2=Hardin |first2=Robert R. |last3=Cockerham |first3=Richard |last4=Yu |first4=Byung P. |last5=Norling |first5=Barry K. |last6=Egan |first6=John W. |title=Lifelong food restriction prevents senile osteopenia and hyperparathyroidism in F344 rats |journal=Mechanisms of Ageing and Development |date=July 1984 |volume=26 |issue=1 |pages=103–112 |doi=10.1016/0047-6374(84)90169-6}}</ref> || {{w|United States}} ({{w|University of Texas Health Science Center at San Antonio}})
+| 1998 || Concept development || || || || The term {{w|caloric restriction mimetic}} is coined by Lane, Ingram, and Roth, of the {{w|National Institute on Aging}} in a seminal paper in the ''Journal of Anti-Aging Medicine'', the forerunner of ''{{w|Rejuvenation Research}}''.<ref name=Lane1998>{{cite journal|author1=Lane MA |author2=Ingram DK |author3=Roth GS|title=2-Deoxy-D-glucose feeding in rats mimics physiologic effects of calorie restriction|journal=J Anti-Aging Med|date=Winter 1998|volume=1|issue=4|pages=327–37|doi=10.1089/rej.1.1998.1.327}}</ref> || {{w|United States}} ({{w|National Institute on Aging}}, {{w|Maryland}})
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-| 1986 || Literature || Lifespan and mortality || || || Richard Weindruch and {{w|Roy Walford}} publish ''The Retardation of Aging and Disease by Dietary Restriction'', an influential and comprehensive encyclopedia of calorie restriction studies that would encourage many scientists to become interested in, and to investigate, calorie restriction and its impact on aging.<ref name="Simpson"/> || {{w|United States}}
+| 1998 || Research || Health || Neutral || Human || Verdery and Walford show that calorie restriction in humans produces physiological effects that are similar to those found in rodents and monkeys.<ref name="The Future of"/>
 |-
-| 1986 || Literature || Lifespan and mortality || || || {{w|Roy Walford}} publishes ''The 120-Year Diet: How to Double Your Vital Years'', advocating the use of calorie restriction to increase human longevity.<ref name="Speakman"/><ref>{{cite book |last1=Leary |first1=Timothy |title=Alternatives to Involuntary Death |date=1 April 2009 |publisher=Ronin Publishing |isbn=978-1-57951-096-1 |url=https://books.google.com.ar/books?id=h6LoBAAAQBAJ&pg=PA57&dq=The+120-Year+Diet:+How+to+Double+Your+Vital+Years&hl=en&sa=X&ved=2ahUKEwjFhtjt4MnxAhVUHbkGHQP0CkUQ6AEwCHoECAsQAg#v=onepage&q=The%20120-Year%20Diet%3A%20How%20to%20Double%20Your%20Vital%20Years&f=false |language=en}}</ref> || {{w|United States}}
+| 1998 || Research || Metabolic effect ({{w|oxidative stress}}) || Helpful || {{w|Rodent}} ({{w|rat}}) || Study by M.V. Aksenova and colleagues in rats concludes that calorie restriction relieves age-associated levels of oxidative stress and lessen protein damage in the brain.<ref>{{cite journal |last1=Aksenova |first1=Marina V |last2=Aksenov |first2=Michael Y |last3=Carney |first3=John M |last4=Butterfield |first4=D.Allan |title=Protein oxidation and enzyme activity decline in old brown Norway rats are reduced by dietary restriction |journal=Mechanisms of Ageing and Development |date=January 1998 |volume=100 |issue=2 |pages=157–168 |doi=10.1016/s0047-6374(97)00133-4}}</ref> || {{w|United States}} ({{w|University of Kentucky}})
 |-
-| 1987 || Research || Behavior ({{w|physical activity}}) || || || Study by D E Harrison and J R Archer reports that the response shown by many rodents to calorie restriction is actually to increase levels of activity.<ref>{{cite journal |last1=Harrison |first1=D. E. |last2=Archer |first2=J. R. |title=Genetic Differences in Effects of Food Restriction on Aging in Mice |journal=The Journal of Nutrition |date=1987-02-01 |volume=117 |issue=2 |pages=376–382 |doi=10.1093/jn/117.2.376}}</ref><ref name="Speakman"/>
+| 1998 || Research || Health (insulin resistance and metabolic syndrome) || Helpful || {{w|Rodent}} ({{w|rat}}) || Research by Barzilai et al. in rats shows that calorie restriction for 18 months restores hepatic insulin sensitivity to the same levels observed in young rats (4 months). Aging is accompanied by a marked increase in hepatic resistance to the action of insulin.<ref>{{cite journal |last1=Barzilai |first1=N |last2=Banerjee |first2=S |last3=Hawkins |first3=M |last4=Chen |first4=W |last5=Rossetti |first5=L |title=Caloric restriction reverses hepatic insulin resistance in aging rats by decreasing visceral fat. |journal=Journal of Clinical Investigation |date=1998-04-01 |volume=101 |issue=7 |pages=1353–1361 |doi=10.1172/JCI485}}</ref> || {{w|United States}} ({{w|Albert Einstein College of Medicine}}, New York)
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-| 1988 || Literature || Lifespan and mortality || || || {{w|Roy Walford}} and Richard Weindruch publish ''The Retardation of Aging and Disease by Dietary Restriction''.<ref name="Speakman"/> || {{w|United States}}
+| 1999 || Research || Health (cancer) || Neutral || {{w|Rodent}} ({{w|mouse}}) || Study by Pugh et al. in mice shows that calorie restriction performed from the age of 12 months onwards resunts in the incidence of the most prevalent cancer (plasma cell neoplasm) being higher in calorie restricted mice (66%) than in controls (41%). However calorie restriction is found to increase the age at which tumor-bearing mice died, also reducing the percentage of mice dying with cancers, suggesting that CR retards the promotion and/or progression of existing lymphoid cancers.<ref>{{cite journal |last1=Pugh |first1=TD |last2=Oberley |first2=TD |last3=Weindruch |first3=R |title=Dietary intervention at middle age: caloric restriction but not dehydroepiandrosterone sulfate increases lifespan and lifetime cancer incidence in mice. |journal=Cancer research |date=1999-04-01 |volume=59 |issue=7 |pages=1642-8 |pmid=10197641}}</ref> || {{w|United States}} (Institute on Aging, {{w|University of Wisconsin–Madison}})
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-| 1991–1993 || Diet introduction || || || || {{w|Roy Walford}}'s compiled data during his participation in {{w|Biosphere 2}} is used to develop the {{w|CRON-diet}}, jointly with Lisa Walford, and {{w|Brian M. Delaney}}. IT consists in eating a diet low in fat and in calories but "nutrient-dense".<ref>{{Cite journal | pmid = 1454844 | year = 1992 | last= Walford | first = R. L. | title = The calorically restricted low-fat nutrient-dense diet in Biosphere 2 significantly lowers blood glucose, total leukocyte count, cholesterol, and blood pressure in humans| journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 89 | issue = 23 | pages = 11533–11537 | last2 = Harris | first2 = S. B. | last3 = Gunion | first3 = M. W. | pmc = 50586  | doi=10.1073/pnas.89.23.11533}}</ref><ref name="Nagourney NYT 2000">{{cite news |last1=Nagourney |first1=Eric |title=Ups and Downs for Diet Guinea Pigs |url=https://www.nytimes.com/2000/09/26/science/ups-and-downs-for-diet-guinea-pigs.html |work={{w|The New York Times}} |date=26 September 2000}}</ref> || {{w|United States}}
+| 1999 || Research || Mortality || Helpful || {{w|Monkey}} || Study by Roth et al. in monkeys suggests that mortality is reduced in subjects on calorie restriction.<ref>{{cite journal |last1=Roth |first1=George S. |last2=Ingram |first2=Donald K. |last3=Lane |first3=Mark A. |title=Calorie Restriction in Primates: Will It Work and How Will We Know? |journal=Journal of the American Geriatrics Society |date=July 1999 |volume=47 |issue=7 |pages=896–903 |doi=10.1111/j.1532-5415.1999.tb03851.x}}</ref><ref name="Lanevvv"/> || {{w|United States}} ({{w|National Institute of Aging}}, {{w|National Institutes of Health}}, {{w|Baltimore}}, {{w|Maryland}})
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-| 1993 || Research || Organ level effect (liver) || || || Research by Alterman et al. in rats shows that calorie restriction has profound effects on the hepatic microsomal levels and activities of {{w|cytochrome P-450s}}, a [[w:Protein superfamily|superfamily]] of {{w|enzyme}}s containing {{w|heme}} as a [[w:cofactor (biochemistry)|cofactor]] that functions as {{w|monooxygenase}}s.<ref>{{cite journal |last1=Alterman |first1=Michail |last2=Carvan |first2=Michael |last3=Srivastava |first3=Vinod |last4=Leakey |first4=Julian |last5=Hart |first5=Ron |last6=Busbee |first6=David |title=Effects of aging and long-term caloric restriction on hepatic microsomal monooxygenases in female fischer 344 rats: Alterations in basal cytochrome P-450 catalytic activities |journal=AGE |date=January 1993 |volume=16 |issue=1 |pages=1–8 |doi=10.1007/BF02436124}}</ref> || {{w|United States}} ({{w|Texas A&M University}})
+| 2000 || Literature || Longevity || Helpful || Human || R.L. Walford publishes ''Beyond the 120-Year Diet: How to Double Your Vital Years'', which argues that longevity can be significantly increased by a diet that contains all the required nutrients but about a third fewer calories.<ref name="Speakman"/>
 |-
-| 1994 || Organization || Lifespan and mortality || || || {{w|CR Society International}} is founded. This organization sponsors conferences, funds anti-aging research, and offers practical guidance to its members.<ref>{{cite web |title=Embryonic CR Society |url=https://www.crsociety.org/about/history/ |website=crsociety.org |access-date=5 May 2021}}</ref> || {{w|United States}}
+| 2000 || Research || Metabolic effect ({{w|autophagy}}) || Helpful || {{w|Rodent}} ({{w|rat}}) || Study by G.Cavallini and colleagues in rats reports that calorie restriction prevents the age-dependent decline of autophagic {{w|proteolysis}} and improves the sensitivity of liver cells to stimulation of lysosomal degradation.<ref>{{cite journal |last1=Cavallini |first1=G. |last2=Donati |first2=A. |last3=Gori |first3=Z. |last4=Pollera |first4=M. |last5=Bergamini |first5=E. |title=The protection of rat liver autophagic proteolysis from the age-related decline co-varies with the duration of anti-ageing food restriction |journal=Experimental Gerontology |date=March 2001 |volume=36 |issue=3 |pages=497–506 |doi=10.1016/S0531-5565(00)00224-2}}</ref> || {{w|Italy}} (Dipartimento di Patologia sperimentale, Biotecnologie mediche, Infettivologia e Epidemiologia, {{w|Pisa}})
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-| 1994 || Research || Health (cancer) || || || Study by Fu et al. shows that caloric restriction profoundly inhibits liver-tumor formation after initiation by 6-nitrochrysene in male-mice.<ref name="Speakman"/>
+| 2000 || Research || Health (disease) || Helpful || {{w|Monkey}} || Study by Black et al. in monkeys suggests that morbidity, in particular {{w|neoplastic disease}}, is reduced in subjects on calorie restriction.<ref name="Lanevvv">{{cite journal |last1=Lane |first1=Mark A. |last2=Mattison |first2=Julie |last3=Ingram |first3=Donald K. |last4=Roth |first4=George S. |title=Caloric restriction and aging in primates: Relevance to humans and possible CR mimetics |journal=Microscopy Research and Technique |date=15 November 2002 |volume=59 |issue=4 |pages=335–338 |doi=10.1002/jemt.10214}}</ref> ||
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-| 1994 || Research || Metabolic effect ({{w|oxidative stress}}) || || || Study by R.S. Sohal and colleagues in mice reports that isolated mitochondria from subjects under calorie restriction show reductions in {{w|superoxide}} radical production.<ref>{{cite journal |last1=Sohal |first1=Rajindar S. |last2=Ku |first2=Hung-Hai |last3=Agarwal |first3=Sanjiv |last4=Forster |first4=Michael J. |last5=Lal |first5=Harbans |title=Oxidative damage, mitochondrial oxidant generation and antioxidant defenses during aging and in response to food restriction in the mouse |journal=Mechanisms of Ageing and Development |date=May 1994 |volume=74 |issue=1-2 |pages=121–133 |doi=10.1016/0047-6374(94)90104-x}}</ref> || {{w|Unted States}} ({{w|Southern Methodist University}}, {{w|Dallas}})
+| 2001 || Research || Organ level effect (bone) || Harmful || {{w|Monkey}} || Study by Black et al. reports that short term (1 year) calorie restriction in young, 4 years old, male monkeys delayed skeletal maturation and reduced bone mass whereas adult-onset calorie restriction, 19 years old, had no significant effect on bone mass compared with control male monkeys.<ref>{{cite journal |last1=Black |first1=A. |last2=Allison |first2=D.B. |last3=Shapses |first3=S.A. |last4=Tilmont |first4=E.M. |last5=Handy |first5=A.M. |last6=Ingram |first6=D.K. |last7=Roth |first7=G.S. |last8=Lane |first8=M.A. |title=Calorie Restriction and Skeletal Mass in Rhesus Monkeys (Macaca mulatta): Evidence for an Effect Mediated Through Changes in Body Size |journal=The Journals of Gerontology Series A: Biological Sciences and Medical Sciences |date=2001-03-01 |volume=56 |issue=3 |pages=B98–B107 |doi=10.1093/gerona/56.3.B98}}</ref> || {{w|United States}} (Gerontology Research Center, {{w|National Institute on Aging}}, {{w|Baltimore}})
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-| 1995 || Research || Behavior (cognitive effect) || || || Study by M W Green et al. concludes that short-term food deprivation has little or no detrimental effect on cognitive function, also indicating that "deficits in cognitive function found to be associated with spontaneous dieting are unlikely to be due primarily to any direct physiological or nutritional effects of food deprivation".<ref>{{cite journal |last1=Green |first1=Michael W. |last2=Elliman |first2=Nicola A. |last3=Rogers |first3=Peter J. |title=Lack of effect of short-term fasting on cognitive function |journal=Journal of Psychiatric Research |date=May 1995 |volume=29 |issue=3 |pages=245–253 |doi=10.1016/0022-3956(95)00009-t}}</ref> || {{w|United Kingdom}} (Institute of Food Research, {{w|Reading, Berkshire}})
+| 2001 || Research || Organ level effect (skin) || Helpful || {{w|Rodent}} ({{w|rat}}) || Research by N.M. Elsayed in rodents reports that oxidative protection of the lung tissue is enhanced by calorie restriction and rats under CR exposed to ozone show lowered oxidative damage and elevated survivability.<ref>{{cite journal |last1=Elsayed |first1=Nabil M |title=Diet restriction modulates lung response and survivability of rats exposed to ozone |journal=Toxicology |date=February 2001 |volume=159 |issue=3 |pages=171–182 |doi=10.1016/s0300-483x(00)00427-3}}</ref> || {{w|United States}} ({{w|Walter Reed Army Institute of Research}}, {{w|Washington, D.C.}})
 |-
-| 1995 || Literature || Longevity || || || {{w|Roy Walford}} publishes ''The Anti-Aging Plan'', which promotes calorie restriction in humans.<ref name="Speakman"/>
+| 2001 || Research || Health ({{w|obesity}}) || Helpful || Human || A review by P. Mustajoki and T. Pekkarinen finds that the {{w|very-low-calorie diet}} in the treatment of {{w|obesity}} has no serious harmful effect when done under medical supervision, for periods of 8–16 weeks with an average weight loss of 1.5-2.5 kg/week.<ref name="Mustajoki2001">{{cite journal |last1=Mustajoki |first1=P. |last2=Pekkarinen |first2=T. |title=Very low energy diets in the treatment of obesity |journal=Obesity Reviews |date=February 2001 |volume=2 |issue=1 |pages=61–72 |doi=10.1046/j.1467-789x.2001.00026.x}}</ref> || {{w|Finland}} (Peijas Hospital, Department of Medicine, {{w|Vantaa}})
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-| 1995 || Research || Endocrine effect (leptin and other adipokines) || || || Study by Robert C. Frederich and colleagues in mice shows that the loss of body fat during calorie restriction results in profound reductions in circulating levels of several {{w|adipokine}}s, including {{w|leptin}}.<ref>{{cite journal |last1=Frederich |first1=Robert C. |last2=Hamann |first2=Andreas |last3=Anderson |first3=Stephen |last4=Löllmann |first4=Bettina |last5=Lowell |first5=Bradford B. |last6=Flier |first6=Jeffrey S. |title=Leptin levels reflect body lipid content in mice: Evidence for diet-induced resistance to leptin action |journal=Nature Medicine |date=December 1995 |volume=1 |issue=12 |pages=1311–1314 |doi=10.1038/nm1295-1311}}</ref> || {{w|United States}} (Beth Israel Hospital, {{w|Boston}}, {{w|Massachusetts}})
+| 2001 || Research || Behavior (reproduction) || Harmful || {{w|Rodent}} || Research by Caprio et al. in rodents reports that when female animals are under calorie restriction their fertility is reduced, presumably as a mechanism to prevent them becoming pregnant at a time when insufficient resources are available to support a reproductive event.<ref>{{cite journal |last1=Caprio |first1=Massimiliano |last2=Fabbrini |first2=Elisa |last3=Isidori |first3=Andrea M |last4=Aversa |first4=Antonio |last5=Fabbri |first5=Andrea |title=Leptin in reproduction |journal=Trends in Endocrinology & Metabolism |date=March 2001 |volume=12 |issue=2 |pages=65–72 |doi=10.1016/S1043-2760(00)00352-0}}</ref> || {{w|Italy}} (Universita’ di Tor Vergata, Università La Sapienza)
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-| 1996 || Research || Metabolic effect ({{w|oxidative stress}}) || || || Study by B.P. Yu in mice concludes that calorie restriction in subjects reduces oxidative stress.<ref>{{cite journal |last1=Yu |first1=Byung Pal |title=Aging and oxidative stress: Modulation by dietary restriction |journal=Free Radical Biology and Medicine |date=January 1996 |volume=21 |issue=5 |pages=651–668 |doi=10.1016/0891-5849(96)00162-1}}</ref> || {{w|United States}} (University of Texas Health Science Center, San Antonio)
+| 2002 || Research || Behavior (hunger) || Neutral || Human || Study by Hansen et al. reports that circulating levels of ghrelin, an {{w|orexigenic hormone}} secreted by the stomach, is increased in the plasma during diet induced weight loss in obese humans, suggesting that {{w|ghrelin}} may contribute to the sustained appetite associated with calorie restriction.<ref>{{cite journal |last1=Hansen |first1=Troels Krarup |last2=Dall |first2=Rolf |last3=Hosoda |first3=Hiroshi |last4=Kojima |first4=Masayasu |last5=Kangawa |first5=Kenji |last6=Christiansen |first6=Jens Sandahl |last7=Jørgensen |first7=Jens Otto Lunde |title=Weight loss increases circulating levels of ghrelin in human obesity: Weight loss and ghrelin |journal=Clinical Endocrinology |date=February 2002 |volume=56 |issue=2 |pages=203–206 |doi=10.1046/j.0300-0664.2001.01456.x}}</ref><ref name="Speakman"/> || {{w|Denmark}} (Aarhus University Hospital), {{w|Japan}} (National Cardiovascular Center Research Institute, Osaka)
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-| 1997 || Research || Health (cancer) || || || Study by Hart and Turturro in rodents reports that calorie restriction in subjects reduces the susceptibility to cancer.<ref>{{cite journal |last1=Hart |first1=R W |last2=Turturro |first2=A |title=Dietary restrictions and cancer. |journal=Environmental Health Perspectives |date=June 1997 |volume=105 |issue=suppl 4 |pages=989–992 |doi=10.1289/ehp.97105s4989}}</ref> || {{w|United States}} ({{w|National Center for Toxicological Research}}, [[w:Jefferson, Jefferson County, Arkansas|Jefferson]], {{w|Arkansas}})
+| 2002 || Research || Longevity || Helpful || Multiple species || According to paper by Lane et al., there are more than 2,000 animal studies on calorie restriction showing dramatic results across many different species, which provide good evidence that restricting calories slows down aging and can extend youthfulness.<ref name="The Future of">{{cite journal |title=The Future of Aging: Pathways to Human Life Extension |date=2010 |doi=10.1007/978-90-481-3999-6}}</ref> ||
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-| 1997 || Research || Organ level effect (alimentary tract) || || || Study by Casirola et al. in mice reports tha intestinal nutrient uptake in calorie restriction animals is significantly higher for D-sugars, L amino acids and L-glucose than in same-age ''{{w|ad libitum}}'' animals.<ref>{{cite journal |last1=Casirola |first1=D. M. |last2=Lan |first2=Y. |last3=Ferraris |first3=R. P. |title=Effects of Changes in Calorie Intake on Intestinal Nutrient Uptake and Transporter mRNA Levels in Aged Mice |journal=The Journals of Gerontology Series A: Biological Sciences and Medical Sciences |date=1997-11-01 |volume=52A |issue=6 |pages=B300–B310 |doi=10.1093/gerona/52a.6.b300}}</ref> || {{w|United States}} ({{w|University of Medicine and Dentistry of New Jersey}})
+| 2003 || Research || Lifespan and mortality || Harmful || {{w|Rodent}} || Research in rodents by Forster et al. shows that the effect of calorie restriction may be negative if the restriction is started very late in life.<ref>{{cite journal |last1=Forster |first1=Michael J. |last2=Morris |first2=Paul |last3=Sohal |first3=Rajindar S. |title=Genotype and age influence the effect of caloric intake on mortality in mice |journal=The FASEB Journal |date=April 2003 |volume=17 |issue=6 |pages=690–692 |doi=10.1096/fj.02-0533fje}}</ref> || {{w|United States}} (Institute for Aging and Alzheimer's Disease Research, {{w|University of North Texas Health Science Center}} at {{w|Fort Worth}})
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-| 1997 || Research || Organ level effect (muscle) || || || Study by Aspnes et al. in mice reports that calorie restriction has a protective effect against sarcopenic muscle loss in subjects.<ref>{{cite journal |last1=Aspnes |first1=Lauren E. |last2=Lee |first2=Connie M. |last3=Weindruch |first3=Richard |last4=Chung |first4=Susan S. |last5=Roecker |first5=Ellen B. |last6=Aiken |first6=Judd M. |title=Caloric restriction reduces fiber loss and mitochondrial abnormalities in aged rat muscle |journal=The FASEB Journal |date=June 1997 |volume=11 |issue=7 |pages=573–581 |doi=10.1096/fasebj.11.7.9212081}}</ref> || {{w|United States}} ({{w|University of Wisconsin–Madison}})
+| 2003 || Research || Endocrine effect ({{w|ghrelin}}) || Neutral || {{w|Rodent}} ({{w|rat}}) || Research by Barazzoni et al. in rats concludes that during calorie restriction, levels of {{w|ghrelin}} are increased.<ref>{{cite journal |last1=Barazzoni |first1=Rocco |last2=Zanetti |first2=Michela |last3=Stebel |first3=Marco |last4=Biolo |first4=Gianni |last5=Cattin |first5=Luigi |last6=Guarnieri |first6=Gianfranco |title=Hyperleptinemia prevents increased plasma ghrelin concentration during short-term moderate caloric restriction in rats |journal=Gastroenterology |date=May 2003 |volume=124 |issue=5 |pages=1188–1192 |doi=10.1016/s0016-5085(03)00281-6 |pmid=12730858}}</ref> || {{w|Italy}} (Dipartmento di Scienze Cliniche, Morfologiche e Technologiche-DSCMT, Clinica Medica, {{w|Trieste}})
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-| 1998 || Research || Health (cancer) || || || Study by T.J. Spady et al. shows that dietary energy restriction abolishes development of prolactin-producing pituitary tumors in rats treated with 17 beta-estradiol.<ref>{{cite journal |last1=Spady |first1=Thomas J. |last2=Lemus-Wilson |first2=Athena M. |last3=Pennington |first3=Karen L. |last4=Blackwood |first4=Darcy J. |last5=Paschall |first5=Tanya M. |last6=Birt |first6=Diane F. |last7=McComb |first7=Rodney D. |last8=Shull |first8=James D. |title=Dietary energy restriction abolishes development of prolactin-producing pituitary tumors in Fischer 344 rats treated with 17-βestradiol |journal=Molecular Carcinogenesis |date=1998 |volume=23 |issue=2 |pages=86–95 |doi=10.1002/(sici)1098-2744(199810)23:2<86::aid-mc5>3.0.co;2-5}}</ref> || {{w|United States}} ({{w|University of Nebraska Medical Center}}, {{w|Omaha}})
+| 2003 || Research || Health (cancer) || Helpful || {{w|Rodent}} ({{w|mouse}}) || A systematic metaanalysis by Dirx et al. of 14 studies in mice suggests that subjects on calorie restriction develop between 41% and 69% less mammary tumors than the control groups.<ref>{{cite journal |last1=Dirx |first1=Miranda J.M. |last2=Zeegers |first2=Maurice P.A. |last3=Dagnelie |first3=Pieter C. |last4=van den Bogaard |first4=Ton |last5=van den Brandt |first5=Piet A. |title=Energy restriction and the risk of spontaneous mammary tumors in mice: A meta-analysis |journal=International Journal of Cancer |date=20 September 2003 |volume=106 |issue=5 |pages=766–770 |doi=10.1002/ijc.11277}}</ref> || {{w|Netherlands}} ({{w|Maastricht University}})
 |-
-| 1998 || Concept development || || || || The term {{w|caloric restriction mimetic}} is coined by Lane, Ingram, and Roth, of the {{w|National Institute on Aging}} in a seminal paper in the ''Journal of Anti-Aging Medicine'', the forerunner of ''{{w|Rejuvenation Research}}''.<ref name=Lane1998>{{cite journal|author1=Lane MA |author2=Ingram DK |author3=Roth GS|title=2-Deoxy-D-glucose feeding in rats mimics physiologic effects of calorie restriction|journal=J Anti-Aging Med|date=Winter 1998|volume=1|issue=4|pages=327–37|doi=10.1089/rej.1.1998.1.327}}</ref> || {{w|United States}} ({{w|National Institute on Aging}}, {{w|Maryland}})
+| 2003 || Research || Organ level effect (bone) || Harmful || {{w|Rodent}} ({{w|rat}}) || Research by LaMothe et al. in rats concludes that axial and appendicular bones are adversely influenced by calorie restriction in late-middle-aged subjects in different manners.<ref>{{cite journal |last1=LaMothe |first1=Jeremy M. |last2=Hepple |first2=Russell T. |last3=Zernicke |first3=Ronald F. |title=Selected Contribution: Bone adaptation with aging and long-term caloric restriction in Fischer 344 × Brown-Norway F1-hybrid rats |journal=Journal of Applied Physiology |date=October 2003 |volume=95 |issue=4 |pages=1739–1745 |doi=10.1152/japplphysiol.00079.2003 |url=}}</ref>
 |-
-| 1998 || Research || Health || || || Verdery and Walford show that calorie restriction in humans produces physiological effects that are similar to those found in rodents and monkeys.<ref name="The Future of"/>
+| 2003 || Research || Longevity || Helpful || {{w|Rodent}} ({{w|mouse}}) || Research by Matthias Blüher et al. in mice suggests that reduced fat mass without calorie restriction can be associated with increased longevity.<ref>{{cite journal |last1=Bluher |first1=M. |title=Extended Longevity in Mice Lacking the Insulin Receptor in Adipose Tissue |journal=Science |date=2003-01-24 |volume=299 |issue=5606 |pages=572–574 |doi=10.1126/science.1078223}}</ref> || {{w|United States}} ({{w|Harvard Medical School}}, {{w|Boston}})
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-| 1998 || Research || Metabolic effect ({{w|oxidative stress}}) || || || Study by M.V. Aksenova and colleagues in rats concludes that calorie restriction relieves age-associated levels of oxidative stress and lessen protein damage in the brain.<ref>{{cite journal |last1=Aksenova |first1=Marina V |last2=Aksenov |first2=Michael Y |last3=Carney |first3=John M |last4=Butterfield |first4=D.Allan |title=Protein oxidation and enzyme activity decline in old brown Norway rats are reduced by dietary restriction |journal=Mechanisms of Ageing and Development |date=January 1998 |volume=100 |issue=2 |pages=157–168 |doi=10.1016/s0047-6374(97)00133-4}}</ref> || {{w|United States}} ({{w|University of Kentucky}})
+| 2003 || Research || Organ level effect (liver) || Harmful || {{w|Rodent}} ({{w|rat}}) || Study by U.M. Apte reports rats under calorie restriction showing increased susceptibility to liver damage induced by the hepatotoxicant thioacetamide.<ref>{{cite journal |last1=Apte |first1=U. M. |title=Mechanisms of Increased Liver Tissue Repair and Survival in Diet-Restricted Rats Treated with Equitoxic Doses of Thioacetamide |journal=Toxicological Sciences |date=2003-04-01 |volume=72 |issue=2 |pages=272–282 |doi=10.1093/toxsci/kfg021}}</ref> || {{w|United States}}
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-| 1998 || Research || Health (insulin resistance and metabolic syndrome) || || || Research by Barzilai et al. in rats shows that calorie restriction for 18 months restores hepatic insulin sensitivity to the same levels observed in young rats (4 months). Aging is accompanied by a marked increase in hepatic resistance to the action of insulin.<ref>{{cite journal |last1=Barzilai |first1=N |last2=Banerjee |first2=S |last3=Hawkins |first3=M |last4=Chen |first4=W |last5=Rossetti |first5=L |title=Caloric restriction reverses hepatic insulin resistance in aging rats by decreasing visceral fat. |journal=Journal of Clinical Investigation |date=1998-04-01 |volume=101 |issue=7 |pages=1353–1361 |doi=10.1172/JCI485}}</ref> || {{w|United States}} ({{w|Albert Einstein College of Medicine}}, New York)
+| 2003 || Research || Endocrine effect ({{w|adiponectin}} || Harmful || {{w|Rodent}} ({{w|mouse}}) || Study by Combs et al. in mice reports increased levels of adiponectin by calorie restriction.<ref>{{cite journal |last1=Combs |first1=T. P. |last2=Berg |first2=A. H. |last3=Rajala |first3=M. W. |last4=Klebanov |first4=S. |last5=Iyengar |first5=P. |last6=Jimenez-Chillaron |first6=J. C. |last7=Patti |first7=M. E. |last8=Klein |first8=S. L. |last9=Weinstein |first9=R. S. |last10=Scherer |first10=P. E. |title=Sexual Differentiation, Pregnancy, Calorie Restriction, and Aging Affect the Adipocyte-Specific Secretory Protein Adiponectin |journal=Diabetes |date=2003-02-01 |volume=52 |issue=2 |pages=268–276 |doi=10.2337/diabetes.52.2.268}}</ref> || {{w|United States}} ({{w|Albert Einstein College of Medicine}})
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-| 1999 || Research || Health (cancer) || || || Study by Pugh et al. in mice shows that calorie restriction performed from the age of 12 months onwards resunts in the incidence of the most prevalent cancer (plasma cell neoplasm) being higher in calorie restricted mice (66%) than in controls (41%). However calorie restriction is found to increase the age at which tumor-bearing mice died, also reducing the percentage of mice dying with cancers, suggesting that CR retards the promotion and/or progression of existing lymphoid cancers.<ref>{{cite journal |last1=Pugh |first1=TD |last2=Oberley |first2=TD |last3=Weindruch |first3=R |title=Dietary intervention at middle age: caloric restriction but not dehydroepiandrosterone sulfate increases lifespan and lifetime cancer incidence in mice. |journal=Cancer research |date=1999-04-01 |volume=59 |issue=7 |pages=1642-8 |pmid=10197641}}</ref> || {{w|United States}} (Institute on Aging, {{w|University of Wisconsin–Madison}})
+| 2004 || Research || Health (immune system) || Helpful || {{w|Rodent}} ({{w|mouse}}) || Research by Christopher A Jolly shows that calorie restriction delays thymic involution in mice.<ref>{{cite journal |last1=Jolly |first1=Christopher A. |title=Dietary Restriction and Immune Function |journal=The Journal of Nutrition |date=2004-08-01 |volume=134 |issue=8 |pages=1853–1856 |doi=10.1093/jn/134.8.1853}}</ref> || {{w|United States}} ({{w|The University of Texas at Austin}})
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-| 1999 || Research || Mortality || || || Study by Roth et al. in monkeys suggests that mortality is reduced in subjects on calorie restriction.<ref>{{cite journal |last1=Roth |first1=George S. |last2=Ingram |first2=Donald K. |last3=Lane |first3=Mark A. |title=Calorie Restriction in Primates: Will It Work and How Will We Know? |journal=Journal of the American Geriatrics Society |date=July 1999 |volume=47 |issue=7 |pages=896–903 |doi=10.1111/j.1532-5415.1999.tb03851.x}}</ref><ref name="Lanevvv"/> || {{w|United States}} ({{w|National Institute of Aging}}, {{w|National Institutes of Health}}, {{w|Baltimore}}, {{w|Maryland}})
+| 2004 || Research || Organ level effect (lungs) || Harmful || {{w|Rodent}} ({{w|rat}}) || Study by Massaro et al. in rats suggests that calorie restriction increases the risk of development of {{w|emphysema}}, a lung condition that causes shortness of breath.<ref>{{cite journal |last1=Masoro |first1=Edward J. |title=Role of sirtuin proteins in life extension by caloric restriction |journal=Mechanisms of Ageing and Development |date=September 2004 |volume=125 |issue=9 |pages=591–594 |doi=10.1016/j.mad.2004.08.011}}</ref> || {{w|United States (University of Texas Health Science Center)
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-| 2000 || Literature || Longevity || || || R.L. Walford publishes ''Beyond the 120-Year Diet: How to Double Your Vital Years''.<ref name="Speakman"/>
+| 2005 || Research || Health (cancer) || Helpful || {{w|Rodent}} ({{w|mouse}}) || Study by Stewart and colleagues in mice shows that skin cancer promotion is inhibited by calorie restriction.<ref>{{cite journal |last1=Stewart |first1=Jeanne W. |last2=Koehler |first2=Ken |last3=Jackson |first3=William |last4=Hawley |first4=Jacqueline |last5=Wang |first5=Weiqun |last6=Au |first6=Angela |last7=Myers |first7=Ron |last8=Birt |first8=Diane F. |title=Prevention of mouse skin tumor promotion by dietary energy restriction requires an intact adrenal gland and glucocorticoid supplementation restores inhibition |journal=Carcinogenesis |date=2005-06-01 |volume=26 |issue=6 |pages=1077–1084 |doi=10.1093/carcin/bgi051}}</ref> || {{w|United States}} ({{w|Iowa State University}})
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-| 2000 || Research || Metabolic effect ({{w|autophagy}}) || || || Study by G.Cavallini and colleagues in rats reports that calorie restriction prevents the age-dependent decline of autophagic proteolysis and improves the sensitivity of liver cells to stimulation of lysosomal degradation.<ref>{{cite journal |last1=Cavallini |first1=G. |last2=Donati |first2=A. |last3=Gori |first3=Z. |last4=Pollera |first4=M. |last5=Bergamini |first5=E. |title=The protection of rat liver autophagic proteolysis from the age-related decline co-varies with the duration of anti-ageing food restriction |journal=Experimental Gerontology |date=March 2001 |volume=36 |issue=3 |pages=497–506 |doi=10.1016/S0531-5565(00)00224-2}}</ref> || {{w|Italy}} (Dipartimento di Patologia sperimentale, Biotecnologie mediche, Infettivologia e Epidemiologia, {{w|Pisa}})
+| 2005 || Research || Organ level effect (skin) || Helpful || {{w|Rodent}} ({{w|rat}}) || Research by Bhattacharyya et al. in rats concludes that calorie restriction retards age related changes on the skin along with increased collagen and elastic fibers, fibroblasts, and capillaries in skin samples from the subjects.<ref>{{cite journal |last1=Bhattacharyya |first1=Tapan K. |last2=Merz |first2=Meredith |last3=Thomas |first3=J. Regan |title=Modulation of Cutaneous Aging With Calorie Restriction in Fischer 344 Rats: A Histological Study |journal=Archives of Facial Plastic Surgery |date=2005-01-01 |volume=7 |issue=1 |pages=12–16 |doi=10.1001/archfaci.7.1.12}}</ref> || {{w|United States}} ({{w|University of Illinois at Chicago}})
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-| 2000 || Research || Health (disease) || || || Study by Black et al. in monkeys suggests that morbidity, in particular {{w|neoplastic disease}}, is reduced in subjects on calorie restriction.<ref name="Lanevvv">{{cite journal |last1=Lane |first1=Mark A. |last2=Mattison |first2=Julie |last3=Ingram |first3=Donald K. |last4=Roth |first4=George S. |title=Caloric restriction and aging in primates: Relevance to humans and possible CR mimetics |journal=Microscopy Research and Technique |date=15 November 2002 |volume=59 |issue=4 |pages=335–338 |doi=10.1002/jemt.10214}}</ref> ||
+| 2005 || Research || Endocrine effect ({{w|insulin}}) || Neutral || {{w|Rodent}} ({{w|mouse}}) || Research by Argentino et al. in mice reports that calorie restriction reduces circulating levels of {{w|insulin-like growth factor 1}} and {{w|insulin}} (and {{w|glucose}}).<ref>{{cite journal |last1=Argentino |first1=D. P. |last2=Muñoz |first2=M. C. |last3=Rocha |first3=J. S. |last4=Bartke |first4=A. |last5=Turyn |first5=D. |last6=Dominici |first6=F. P. |title=Short-term Caloric Restriction Does Not Modify the In Vivo Insulin Signaling Pathway Leading to Akt Activation in Skeletal Muscle of Ames Dwarf (Prop1 df /Prop1 df ) Mice |journal=Hormone and Metabolic Research |date=November 2005 |volume=37 |issue=11 |pages=672–679 |doi=10.1055/s-2005-870577}}</ref><ref>{{cite journal |last1=Argentino |first1=D. P. |last2=Dominici |first2=F. P. |last3=Al-Regaiey |first3=K. |last4=Bonkowski |first4=M. S. |last5=Bartke |first5=A. |last6=Turyn |first6=D. |title=Effects of Long-Term Caloric Restriction on Early Steps of the Insulin-Signaling System in Mouse Skeletal Muscle |journal=The Journals of Gerontology Series A: Biological Sciences and Medical Sciences |date=2005-01-01 |volume=60 |issue=1 |pages=28–34 |doi=10.1093/gerona/60.1.28}}</ref> || {{w|Argentina}} (Instituto de Química y Fisicoquímica Biológicas ([[w:University of Buenos Aires|UBA]]-{{w|CONICET}}), Facultad de Farmacia y Bioquímica, {{w|Buenos Aires}})
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-| 2001 || Research || Organ level effect (bone) || || || Study by Black et al. reports that short term (1 year) calorie restriction in young, 4 years old, male monkeys delayed skeletal maturation and reduced bone mass whereas adult-onset calorie restriction, 19 years old, had no significant effect on bone mass compared with control male monkeys.<ref>{{cite journal |last1=Black |first1=A. |last2=Allison |first2=D.B. |last3=Shapses |first3=S.A. |last4=Tilmont |first4=E.M. |last5=Handy |first5=A.M. |last6=Ingram |first6=D.K. |last7=Roth |first7=G.S. |last8=Lane |first8=M.A. |title=Calorie Restriction and Skeletal Mass in Rhesus Monkeys (Macaca mulatta): Evidence for an Effect Mediated Through Changes in Body Size |journal=The Journals of Gerontology Series A: Biological Sciences and Medical Sciences |date=2001-03-01 |volume=56 |issue=3 |pages=B98–B107 |doi=10.1093/gerona/56.3.B98}}</ref> || {{w|United States}} (Gerontology Research Center, {{w|National Institute on Aging}}, {{w|Baltimore}})
+| 2005 || Research || Metabolic effect ({{w|mitochondrial biogenesis}}) || Helpful || {{w|Rodent}} ({{w|mouse}}) || Study by Enzo Nisoli and colleagues reports that calorie restriction at 30% for 3 months results in mitochondrial biogenesis in the brain, heart, liver and particularly the adipose tissue of mice.<ref>{{cite journal |last1=Nisoli |first1=E. |title=Calorie Restriction Promotes Mitochondrial Biogenesis by Inducing the Expression of eNOS |journal=Science |date=14 October 2005 |volume=310 |issue=5746 |pages=314–317 |doi=10.1126/science.1117728}}</ref> || {{w|Italy}}, {{w|United Kingdom}}
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-| 2001 || Research || Organ level effect (skin) || || || Research by N.M. Elsayed in rodents reports that oxidative protection of the lung tissue is enhanced by calorie restriction and rats under CR exposed to ozone show lowered oxidative damage and elevated survivability.<ref>{{cite journal |last1=Elsayed |first1=Nabil M |title=Diet restriction modulates lung response and survivability of rats exposed to ozone |journal=Toxicology |date=February 2001 |volume=159 |issue=3 |pages=171–182 |doi=10.1016/s0300-483x(00)00427-3}}</ref> || {{w|United States}} ({{w|Walter Reed Army Institute of Research}}, {{w|Washington, D.C.}})
+| 2006 || Research || Behavior (cognitive effects) || Helpful || {{w|Rodent}} ({{w|mouse}}) || Research by Martin et al. reports evidence suggesting that calorie restriction and {{w|intermittent fasting}} may benefit {{w|neuron}}s by impinging upon fundamental metabolic and cellular signaling pathways that regulate life-span.<ref>{{cite journal |last1=Martin |first1=Bronwen |last2=Mattson |first2=Mark P. |last3=Maudsley |first3=Stuart |title=Caloric restriction and intermittent fasting: Two potential diets for successful brain aging |journal=Ageing Research Reviews |date=August 2006 |volume=5 |issue=3 |pages=332–353 |doi=10.1016/j.arr.2006.04.002}}</ref> ||
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-| 2001 || Research || Health || || || A review by P. Mustajoki and T. Pekkarinen finds that the {{w|very-low-calorie diet}} in the treatment of {{w|obesity}} has no serious harmful effect when done under medical supervision, for periods of 8–16 weeks with an average weight loss of 1.5-2.5 kg/week.<ref name="Mustajoki2001">{{cite journal |last1=Mustajoki |first1=P. |last2=Pekkarinen |first2=T. |title=Very low energy diets in the treatment of obesity |journal=Obesity Reviews |date=February 2001 |volume=2 |issue=1 |pages=61–72 |doi=10.1046/j.1467-789x.2001.00026.x}}</ref> || {{w|Finland}} (Peijas Hospital, Department of Medicine, {{w|Vantaa}})
+| 2006 || Research || Behavior (reproduction) || Harmful || {{w|Rabbit}} || Study by Brecchia et al. reports that, in female rabbits, food deprived completely for 24 and 48 hours results in decline in fertility by 23.9 and 21.4% respectively, matched by major disturbances in the endocrine axis linked to reproduction.<ref>{{cite journal |last1=Brecchia |first1=Gabriele |last2=Bonanno |first2=Adriana |last3=Galeati |first3=Giovanna |last4=Federici |first4=Claudia |last5=Maranesi |first5=Margherita |last6=Gobbetti |first6=Anna |last7=Zerani |first7=Massimo |last8=Boiti |first8=Cristiano |title=Hormonal and metabolic adaptation to fasting: Effects on the hypothalamic–pituitary–ovarian axis and reproductive performance of rabbit does |journal=Domestic Animal Endocrinology |date=August 2006 |volume=31 |issue=2 |pages=105–122 |doi=10.1016/j.domaniend.2005.09.006}}</ref> || {{w|Italy}}
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-| 2001 || Research || Behavior (reproduction) || || || Research by Caprio et al. in rodents reports that when female animals are under calorie restriction their fertility is reduced, presumably as a mechanism to prevent them becoming pregnant at a time when insufficient resources are available to support a reproductive event.<ref>{{cite journal |last1=Caprio |first1=Massimiliano |last2=Fabbrini |first2=Elisa |last3=Isidori |first3=Andrea M |last4=Aversa |first4=Antonio |last5=Fabbri |first5=Andrea |title=Leptin in reproduction |journal=Trends in Endocrinology & Metabolism |date=March 2001 |volume=12 |issue=2 |pages=65–72 |doi=10.1016/S1043-2760(00)00352-0}}</ref> || {{w|Italy}} (Universita’ di Tor Vergata, Università La Sapienza)
+| 2007 || Research || Metabolic effect ({{w|oxidative stress}}) || Helpful || {{w|Rodent}} ({{w|rat}}) || Study by Cenk Aydin et al. in rats concludes that subjects on calorie restriction are protected against oxidative stress induced by swimming exercise in the liver, heart and kidney.<ref>{{cite journal |last1=Aydin |first1=Cenk |last2=Ince |first2=Erdal |last3=Koparan |first3=Senay |last4=Cangul |first4=I. Taci |last5=Naziroglu |first5=Mustafa |last6=Ak |first6=Fusun |title=Protective effects of long term dietary restriction on swimming exercise-induced oxidative stress in the liver, heart and kidney of rat |journal=Cell Biochemistry and Function |date=March 2007 |volume=25 |issue=2 |pages=129–137 |doi=10.1002/cbf.1279}}</ref> Two years later, the researchers discover the same effects in the brain and lungs.<ref>{{cite journal |last1=Aydin |first1=C |last2=Sonat |first2=F |last3=Sahin |first3=SK |last4=Cangul |first4=IT |last5=Ozkaya |first5=G |title=Long term dietary restriction ameliorates swimming exercise-induced oxidative stress in brain and lung of middle-aged rat. |journal=Indian journal of experimental biology |date=January 2009 |volume=47 |issue=1 |pages=24-31 |pmid=19317348}}</ref> || {{w|Turkey}} (Uludag University, {{w|Bursa}})
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-| 2002 || Research || Behavior (hunger) || || || Study by Hansen et al. reports that circulating levels of ghrelin, an {{w|orexigenic hormone}} secreted by the stomach, is increased in the plasma during dietinduced weight loss in obese humans, suggesting that {{w|ghrelin}} may contribute to the sustained appetite associated with calorie restriction.<ref>{{cite journal |last1=Hansen |first1=Troels Krarup |last2=Dall |first2=Rolf |last3=Hosoda |first3=Hiroshi |last4=Kojima |first4=Masayasu |last5=Kangawa |first5=Kenji |last6=Christiansen |first6=Jens Sandahl |last7=Jørgensen |first7=Jens Otto Lunde |title=Weight loss increases circulating levels of ghrelin in human obesity: Weight loss and ghrelin |journal=Clinical Endocrinology |date=February 2002 |volume=56 |issue=2 |pages=203–206 |doi=10.1046/j.0300-0664.2001.01456.x}}</ref><ref name="Speakman"/> || {{w|Denmark}} (Aarhus University Hospital), {{w|Japan}} (National Cardiovascular Center Research Institute, Osaka)
+| 2007 || Research || Behavior (cognitive effects) || Neutral || {{w|Rodent}} ({{w|rat}}) || Research by Martin et al. in rats reports no consistent pattern of verbal memory, visual retention/memory, or attention/concentration deficits being found over 6 months, and the energy deficit by calorie restriction or exercise was not significantly associated cognitive test performance.<ref>{{cite journal |last1=Martin |first1=Bronwen |last2=Pearson |first2=Michele |last3=Kebejian |first3=Lisa |last4=Golden |first4=Erin |last5=Keselman |first5=Alex |last6=Bender |first6=Meredith |last7=Carlson |first7=Olga |last8=Egan |first8=Josephine |last9=Ladenheim |first9=Bruce |last10=Cadet |first10=Jean-Lud |last11=Becker |first11=Kevin G. |last12=Wood |first12=William |last13=Duffy |first13=Kara |last14=Vinayakumar |first14=Prabhu |last15=Maudsley |first15=Stuart |last16=Mattson |first16=Mark P. |title=Sex-Dependent Metabolic, Neuroendocrine, and Cognitive Responses to Dietary Energy Restriction and Excess |journal=Endocrinology |date=September 2007 |volume=148 |issue=9 |pages=4318–4333 |doi=10.1210/en.2007-0161}}</ref> ||
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-| 2002 || Research || Longevity || || || According to paper by Lane et al., there are more than 2,000 animal studies on calorie restriction showing dramatic results across many different species, which provide good evidence that restricting calories slows down aging and can extend youthfulness.<ref name="The Future of">{{cite journal |title=The Future of Aging: Pathways to Human Life Extension |date=2010 |doi=10.1007/978-90-481-3999-6}}</ref> ||
+| 2007 || Research || Organ level effect ({{w|alimentary tract}}) || Harmful || {{w|Rodent}} ({{w|mouse}}) || Study by Yang et al. in mice reports what is perhaps the most conspicuous change in the morphology of the alimentary tract under calorie restriction, which is the hypertrophy of the stomach observed in subjects.<ref>{{cite journal |last1=Yang |first1=Hyunwon |last2=Youm |first2=Yun-Hee |last3=Nakata |first3=Chiaki |last4=Dixit |first4=Vishwa Deep |title=Chronic caloric restriction induces forestomach hypertrophy with enhanced ghrelin levels during aging |journal=Peptides |date=October 2007 |volume=28 |issue=10 |pages=1931–1936 |doi=10.1016/j.peptides.2007.07.030}}</ref> || {{w|United States}} ({{w|Louisiana State University System}})
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-| 2003 || Research || Lifespan and mortality || || || Research in rodents by Forster et al. shows that the effect of calorie restriction may be negative if the restriction is started very late in life.<ref>{{cite journal |last1=Forster |first1=Michael J. |last2=Morris |first2=Paul |last3=Sohal |first3=Rajindar S. |title=Genotype and age influence the effect of caloric intake on mortality in mice |journal=The FASEB Journal |date=April 2003 |volume=17 |issue=6 |pages=690–692 |doi=10.1096/fj.02-0533fje}}</ref> || {{w|United States}} (Institute for Aging and Alzheimer's Disease Research, {{w|University of North Texas Health Science Center}} at {{w|Fort Worth}})
+| 2007 || Research || Longevity || Helpful || Human || Stydy by Speakman and Hambly calculates that if the lifespan effects observed in rodents translate faithfully to an effect in humans, then if a 48 year old engaged in 30% calorie restriction for 30 years, until the current mean life-expectancy of 78, they might expect to live only an extra 2.8 years because of the CR effect.<ref>{{cite journal |last1=Speakman |first1=John R. |last2=Hambly |first2=Catherine |title=Starving for Life: What Animal Studies Can and Cannot Tell Us about the Use of Caloric Restriction to Prolong Human Lifespan |journal=The Journal of Nutrition |date=2007-04-01 |volume=137 |issue=4 |pages=1078–1086 |doi=10.1093/jn/137.4.1078}}</ref> ||
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-| 2003 || Research || Endocrine effect ({{w|ghrelin}}) || || || Research by Barazzoni et al. in rats concludes that during calorie restriction, levels of {{w|ghrelin}} are increased.<ref>{{cite journal |last1=Barazzoni |first1=Rocco |last2=Zanetti |first2=Michela |last3=Stebel |first3=Marco |last4=Biolo |first4=Gianni |last5=Cattin |first5=Luigi |last6=Guarnieri |first6=Gianfranco |title=Hyperleptinemia prevents increased plasma ghrelin concentration during short-term moderate caloric restriction in rats |journal=Gastroenterology |date=May 2003 |volume=124 |issue=5 |pages=1188–1192 |doi=10.1016/s0016-5085(03)00281-6 |pmid=12730858}}</ref> || {{w|Italy}} (Dipartmento di Scienze Cliniche, Morfologiche e Technologiche-DSCMT, Clinica Medica, {{w|Trieste}})
+| 2007 || Research || Organ level effect (kidney) || Helpful || {{w|Rodent}} || Research by Chen et al. in rodents concludes that calorie restriction attenuates increased susceptibility to kidney injury in old subjects.<ref>{{cite journal |last1=Chen |first1=G. |last2=Bridenbaugh |first2=E. A. |last3=Akintola |first3=A. D. |last4=Catania |first4=J. M. |last5=Vaidya |first5=V. S. |last6=Bonventre |first6=J. V. |last7=Dearman |first7=A. C. |last8=Sampson |first8=H. W. |last9=Zawieja |first9=D. C. |last10=Burghardt |first10=R. C. |last11=Parrish |first11=A. R. |title=Increased susceptibility of aging kidney to ischemic injury: identification of candidate genes changed during aging, but corrected by caloric restriction |journal=American Journal of Physiology-Renal Physiology |date=October 2007 |volume=293 |issue=4 |pages=F1272–F1281 |doi=10.1152/ajprenal.00138.2007}}</ref> || {{w|United States}} ({{w|Texas A&M Health Science Center}})
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-| 2003 || Research || Health (cancer) || || || A systematic metaanalysis by Dirx et al. of 14 studies in mice suggests that subjects on calorie restriction develop between 41% and 69% less mammary tumors than the control groups.<ref>{{cite journal |last1=Dirx |first1=Miranda J.M. |last2=Zeegers |first2=Maurice P.A. |last3=Dagnelie |first3=Pieter C. |last4=van den Bogaard |first4=Ton |last5=van den Brandt |first5=Piet A. |title=Energy restriction and the risk of spontaneous mammary tumors in mice: A meta-analysis |journal=International Journal of Cancer |date=20 September 2003 |volume=106 |issue=5 |pages=766–770 |doi=10.1002/ijc.11277}}</ref> || {{w|Netherlands}} ({{w|Maastricht University}})
+| 2008 || Research || Health (cancer) || Helpful || {{w|Rodent}} ({{w|mouse}}) || Study by Wheatley et al. in mice suggests that although a low calorie diet does not induce weight loss, it may reduce {{w|colon cancer}} risk by lowering serum IGF-I levels.<ref>{{cite journal |last1=Wheatley |first1=Karrie E. |last2=Williams |first2=Elizabeth A. |last3=Smith |first3=Nicole C. P. |last4=Dillard |first4=Alice |last5=Park |first5=Eun Young |last6=Nunez |first6=Nomeli P. |last7=Hursting |first7=Stephen D. |last8=Lane |first8=Michelle A. |title=Low-Carbohydrate Diet Versus Caloric Restriction: Effects on Weight Loss, Hormones, and Colon Tumor Growth in Obese Mice |journal=Nutrition and Cancer |date=2007-12-28 |volume=60 |issue=1 |pages=61–68 |doi=10.1080/01635580701510150}}</ref> || {{w|United States}} ({{w|University of Texas at Austin}})
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-| 2003 || Research || Organ level effect (bone) || || || Research by LaMothe et al. in rats concludes that axial and appendicular bones are adversely influenced by calorie restriction in late-middle-aged subjects in different manners.<ref>{{cite journal |last1=LaMothe |first1=Jeremy M. |last2=Hepple |first2=Russell T. |last3=Zernicke |first3=Ronald F. |title=Selected Contribution: Bone adaptation with aging and long-term caloric restriction in Fischer 344 × Brown-Norway F1-hybrid rats |journal=Journal of Applied Physiology |date=October 2003 |volume=95 |issue=4 |pages=1739–1745 |doi=10.1152/japplphysiol.00079.2003 |url=}}</ref>
+| 2008 || Research || Organ level effect (bone) || Harmful || {{w|Rodent}} ({{w|rat}}) || Research by Baek et al. in rats concludes that moderate caloric restriction may cause bone loss at susceptible bone sites to a similar degree as does the unloading effect of microgravity in astronauts.<ref>{{cite journal |last1=Baek |first1=Kyunghwa |last2=Barlow |first2=Alicia A. |last3=Allen |first3=Matt R. |last4=Bloomfield |first4=Susan A. |title=Food restriction and simulated microgravity: effects on bone and serum leptin |journal=Journal of Applied Physiology |date=April 2008 |volume=104 |issue=4 |pages=1086–1093 |doi=10.1152/japplphysiol.01209.2007}}</ref> ||
 |-
-| 2003 || Research || Longevity || || || Research by Matthias Blüher et al. in mice suggests that reduced fat mass without calorie restriction can be associated with increased longevity.<ref>{{cite journal |last1=Bluher |first1=M. |title=Extended Longevity in Mice Lacking the Insulin Receptor in Adipose Tissue |journal=Science |date=2003-01-24 |volume=299 |issue=5606 |pages=572–574 |doi=10.1126/science.1078223}}</ref> || {{w|United States}} ({{w|Harvard Medical School}}, {{w|Boston}})
+| 2008 || Research || Organ level effect (muscle) || Helpful || Non-human primate || Study by Colman et al. reports that calorie restriction has a protective effect against sarcopenic muscle loss in non-human primates.<ref>{{cite journal |last1=Colman |first1=R. J. |last2=Beasley |first2=T. M. |last3=Allison |first3=D. B. |last4=Weindruch |first4=R. |title=Attenuation of Sarcopenia by Dietary Restriction in Rhesus Monkeys |journal=The Journals of Gerontology Series A: Biological Sciences and Medical Sciences |date=2008-06-01 |volume=63 |issue=6 |pages=556–559 |doi=10.1093/gerona/63.6.556}}</ref> || {{w|United States}} (Wisconsin National Primate Research Center, {{w|University of Wisconsin-Madison}})
 |-
-| 2003 || Research || Organ level effect (liver) || || || Study by U.M. Apte reports rats under calorie restriction showing increased susceptibility to liver damage induced by the hepatotoxicant thioacetamide.<ref>{{cite journal |last1=Apte |first1=U. M. |title=Mechanisms of Increased Liver Tissue Repair and Survival in Diet-Restricted Rats Treated with Equitoxic Doses of Thioacetamide |journal=Toxicological Sciences |date=2003-04-01 |volume=72 |issue=2 |pages=272–282 |doi=10.1093/toxsci/kfg021}}</ref> || {{w|United States}}
+| 2014 || Recommendation || || || || According to the [[w:National Institute for Health and Care Excellence|NICE]] 2014 guidelines, the routine use of {{w|very-low-calorie diet}}s is not recommended due to safety concerns, but this approach can be used under medical supervision if there is a clinical rationale for rapid weight loss in obese individuals, as part of a "multi-component weight management strategy" with continuous support and for a maximum of 12 weeks.<ref name="Overview {{!}} Obesit">{{cite web |title=Overview {{!}} Obesity: identification, assessment and management {{!}} Guidance {{!}} NICE |url=https://www.nice.org.uk/guidance/cg189 |website=www.nice.org.uk |access-date=24 June 2021}}</ref> ||
 |-
-| 2003 || Research || Endocrine effect ({{w|adiponectin}} || || || Study by Combs et al. in mice reports increased levels of adiponectin by calorie restriction.<ref>{{cite journal |last1=Combs |first1=T. P. |last2=Berg |first2=A. H. |last3=Rajala |first3=M. W. |last4=Klebanov |first4=S. |last5=Iyengar |first5=P. |last6=Jimenez-Chillaron |first6=J. C. |last7=Patti |first7=M. E. |last8=Klein |first8=S. L. |last9=Weinstein |first9=R. S. |last10=Scherer |first10=P. E. |title=Sexual Differentiation, Pregnancy, Calorie Restriction, and Aging Affect the Adipocyte-Specific Secretory Protein Adiponectin |journal=Diabetes |date=2003-02-01 |volume=52 |issue=2 |pages=268–276 |doi=10.2337/diabetes.52.2.268}}</ref> || {{w|United States}} ({{w|Albert Einstein College of Medicine}})
+| 2018 || Research || Health (brain) || Helpful/harmful || {{w|Grey mouse lemur}} || Researchers find that {{w|caloric restriction}} increases lifespan but affects brain integrity in {{w|grey mouse lemur}} primates.<ref>{{cite journal |last1=Pifferi |first1=Fabien |last2=Terrien |first2=Jérémy |last3=Marchal |first3=Julia |last4=Dal-Pan |first4=Alexandre |last5=Djelti |first5=Fathia |last6=Hardy |first6=Isabelle |last7=Chahory |first7=Sabine |last8=Cordonnier |first8=Nathalie |last9=Desquilbet |first9=Loïc |last10=Hurion |first10=Murielle |last11=Zahariev |first11=Alexandre |last12=Chery |first12=Isabelle |last13=Zizzari |first13=Philippe |last14=Perret |first14=Martine |last15=Epelbaum |first15=Jacques |last16=Blanc |first16=Stéphane |last17=Picq |first17=Jean-Luc |last18=Dhenain |first18=Marc |last19=Aujard |first19=Fabienne |title=Caloric restriction increases lifespan but affects brain integrity in grey mouse lemur primates |journal=Communications Biology |date=December 2018 |volume=1 |issue=1 |pages=30 |doi=10.1038/s42003-018-0024-8}}</ref> || {{w|France}}
 |-
-| 2004 || Research || Health (immune system) || || || Research by Christopher A Jolly shows that calorie restriction delays thymic involution in mice.<ref>{{cite journal |last1=Jolly |first1=Christopher A. |title=Dietary Restriction and Immune Function |journal=The Journal of Nutrition |date=2004-08-01 |volume=134 |issue=8 |pages=1853–1856 |doi=10.1093/jn/134.8.1853}}</ref> || {{w|United States}} ({{w|The University of Texas at Austin}})
+|}
+== Numerical and visual data ==
+=== Mentions on Google Scholar ===
+{| class="sortable wikitable"
+! Year
+! calorie restriction
+! calorie restriction benefits
+! calorie restriction weight loss
+! calorie restriction longevity
+! calorie restriction oxidative stress
 |-
-| 2004 || Research || Organ level effect (lungs) || || || Study by Massaro et al. suggests that calorie restriction increases the risk of development of {{w|emphysema}}, a lung condition that causes shortness of breath.<ref>{{cite journal |last1=Masoro |first1=Edward J. |title=Role of sirtuin proteins in life extension by caloric restriction |journal=Mechanisms of Ageing and Development |date=September 2004 |volume=125 |issue=9 |pages=591–594 |doi=10.1016/j.mad.2004.08.011}}</ref> || {{w|United States (University of Texas Health Science Center)
+| 1980 || 444 || 236 || 714 || 67 || 53
 |-
-| 2005 || Research || Health (cancer) || || || Study by Stewart et al. shows that skin cancer promotion is inhibited by calorie restriction.<ref>{{cite journal |last1=Stewart |first1=Jeanne W. |last2=Koehler |first2=Ken |last3=Jackson |first3=William |last4=Hawley |first4=Jacqueline |last5=Wang |first5=Weiqun |last6=Au |first6=Angela |last7=Myers |first7=Ron |last8=Birt |first8=Diane F. |title=Prevention of mouse skin tumor promotion by dietary energy restriction requires an intact adrenal gland and glucocorticoid supplementation restores inhibition |journal=Carcinogenesis |date=2005-06-01 |volume=26 |issue=6 |pages=1077–1084 |doi=10.1093/carcin/bgi051}}</ref> || {{w|United States}} ({{w|Iowa State University}})
+| 1985 || 597 || 327 || 956 || 111 || 81
 |-
-| 2005 || Research || Organ level effect (skin) || || || Research by Bhattacharyya et al. in rats concludes that calorie restriction retards age related changes on the skin along with increased collagen and elastic fibers, fibroblasts, and capillaries in skin samples from the subjects.<ref>{{cite journal |last1=Bhattacharyya |first1=Tapan K. |last2=Merz |first2=Meredith |last3=Thomas |first3=J. Regan |title=Modulation of Cutaneous Aging With Calorie Restriction in Fischer 344 Rats: A Histological Study |journal=Archives of Facial Plastic Surgery |date=2005-01-01 |volume=7 |issue=1 |pages=12–16 |doi=10.1001/archfaci.7.1.12}}</ref> || {{w|United States}} ({{w|University of Illinois at Chicago}})
+| 1990 || 778 || 544 || 1,280 || 176 || 164
 |-
-| 2005 || Research || Endocrine effect ({{w|insulin}}) || || || Research by Argentino et al. in mice reports that calorie restriction reduces circulating levels of {{w|insulin-like growth factor 1}} and {{w|insulin}} (and {{w|glucose}}).<ref>{{cite journal |last1=Argentino |first1=D. P. |last2=Muñoz |first2=M. C. |last3=Rocha |first3=J. S. |last4=Bartke |first4=A. |last5=Turyn |first5=D. |last6=Dominici |first6=F. P. |title=Short-term Caloric Restriction Does Not Modify the In Vivo Insulin Signaling Pathway Leading to Akt Activation in Skeletal Muscle of Ames Dwarf (Prop1 df /Prop1 df ) Mice |journal=Hormone and Metabolic Research |date=November 2005 |volume=37 |issue=11 |pages=672–679 |doi=10.1055/s-2005-870577}}</ref><ref>{{cite journal |last1=Argentino |first1=D. P. |last2=Dominici |first2=F. P. |last3=Al-Regaiey |first3=K. |last4=Bonkowski |first4=M. S. |last5=Bartke |first5=A. |last6=Turyn |first6=D. |title=Effects of Long-Term Caloric Restriction on Early Steps of the Insulin-Signaling System in Mouse Skeletal Muscle |journal=The Journals of Gerontology Series A: Biological Sciences and Medical Sciences |date=2005-01-01 |volume=60 |issue=1 |pages=28–34 |doi=10.1093/gerona/60.1.28}}</ref> || {{w|Argentina}} (Instituto de Química y Fisicoquímica Biológicas ([[w:University of Buenos Aires|UBA]]-{{w|CONICET}}), Facultad de Farmacia y Bioquímica, {{w|Buenos Aires}})
+| 1995 || 1,070 || 857 || 1,760 || 281 || 317
 |-
-| 2005 || Research || Metabolic effect ({{w|mitochondrial biogenesis}}) || || || Study by Enzo Nisoli and colleagues reports that calorie restriction at 30% for 3 months results in mitochondrial biogenesis in the brain, heart, liver and particularly the adipose tissue of mice.<ref>{{cite journal |last1=Nisoli |first1=E. |title=Calorie Restriction Promotes Mitochondrial Biogenesis by Inducing the Expression of eNOS |journal=Science |date=14 October 2005 |volume=310 |issue=5746 |pages=314–317 |doi=10.1126/science.1117728}}</ref> || {{w|Italy}}, {{w|United Kingdom}}
+| 2000 || 1,880 || 1,500 || 2,850 || 559 || 1,230
 |-
-| 2006 || Research || Behavior (cognitive effects) || || || Research by Martin et al. reports evidence suggesting that calorie restriction and {{w|intermittent fasting}} may benefit {{w|neuron}}s by impinging upon fundamental metabolic and cellular signaling pathways that regulate life-span.<ref>{{cite journal |last1=Martin |first1=Bronwen |last2=Mattson |first2=Mark P. |last3=Maudsley |first3=Stuart |title=Caloric restriction and intermittent fasting: Two potential diets for successful brain aging |journal=Ageing Research Reviews |date=August 2006 |volume=5 |issue=3 |pages=332–353 |doi=10.1016/j.arr.2006.04.002}}</ref> ||
+| 2002 || 2,560 || 1,840 || 3,910 || 786 || 1,790
 |-
-| 2006 || Research || Behavior (reproduction) || || || Study by Brecchia et al. reports that, in female rabbits, food deprived completely for 24 and 48 hours results in decline in fertility by 23.9 and 21.4% respectively, matched by major disturbances in the endocrine axis linked to reproduction.<ref>{{cite journal |last1=Brecchia |first1=Gabriele |last2=Bonanno |first2=Adriana |last3=Galeati |first3=Giovanna |last4=Federici |first4=Claudia |last5=Maranesi |first5=Margherita |last6=Gobbetti |first6=Anna |last7=Zerani |first7=Massimo |last8=Boiti |first8=Cristiano |title=Hormonal and metabolic adaptation to fasting: Effects on the hypothalamic–pituitary–ovarian axis and reproductive performance of rabbit does |journal=Domestic Animal Endocrinology |date=August 2006 |volume=31 |issue=2 |pages=105–122 |doi=10.1016/j.domaniend.2005.09.006}}</ref> || {{w|Italy}}
+| 2004 || 3,380 || 2,550 || 4,600 || 1,120 || 2,260
 |-
-| 2007 || Research || Metabolic effect ({{w|oxidative stress}}) || || || Study by Cenk Aydin et al. in rats concludes that subjects on calorie restriction are protected against oxidative stress induced by swimming exercise in the liver, heart and kidney.<ref>{{cite journal |last1=Aydin |first1=Cenk |last2=Ince |first2=Erdal |last3=Koparan |first3=Senay |last4=Cangul |first4=I. Taci |last5=Naziroglu |first5=Mustafa |last6=Ak |first6=Fusun |title=Protective effects of long term dietary restriction on swimming exercise-induced oxidative stress in the liver, heart and kidney of rat |journal=Cell Biochemistry and Function |date=March 2007 |volume=25 |issue=2 |pages=129–137 |doi=10.1002/cbf.1279}}</ref> Two years later, the researchers discover the same effects in the brain and lungs.<ref>{{cite journal |last1=Aydin |first1=C |last2=Sonat |first2=F |last3=Sahin |first3=SK |last4=Cangul |first4=IT |last5=Ozkaya |first5=G |title=Long term dietary restriction ameliorates swimming exercise-induced oxidative stress in brain and lung of middle-aged rat. |journal=Indian journal of experimental biology |date=January 2009 |volume=47 |issue=1 |pages=24-31 |pmid=19317348}}</ref> || {{w|Turkey}} (Uludag University, {{w|Bursa}})
+| 2006 || 4,340 || 3,350 || 6,330 || 1,410 || 3,110
 |-
-| 2007 || Research || Behavior (cognitive effects) || || || Research by Martin et al. in rats reports no consistent pattern of verbal memory, visual retention/memory, or attention/concentration deficits being found over 6 months, and the energy deficit by calorie restriction or exercise was not significantly associated cognitive test performance.<ref>{{cite journal |last1=Martin |first1=Bronwen |last2=Pearson |first2=Michele |last3=Kebejian |first3=Lisa |last4=Golden |first4=Erin |last5=Keselman |first5=Alex |last6=Bender |first6=Meredith |last7=Carlson |first7=Olga |last8=Egan |first8=Josephine |last9=Ladenheim |first9=Bruce |last10=Cadet |first10=Jean-Lud |last11=Becker |first11=Kevin G. |last12=Wood |first12=William |last13=Duffy |first13=Kara |last14=Vinayakumar |first14=Prabhu |last15=Maudsley |first15=Stuart |last16=Mattson |first16=Mark P. |title=Sex-Dependent Metabolic, Neuroendocrine, and Cognitive Responses to Dietary Energy Restriction and Excess |journal=Endocrinology |date=September 2007 |volume=148 |issue=9 |pages=4318–4333 |doi=10.1210/en.2007-0161}}</ref> ||
+| 2008 || 5,500 || 4,080 || 8,020 || 1,780 || 4,090
 |-
-| 2007 || Research || Organ level effect ({{w|alimentary tract}}) || || || Study by Yang et al. in mice reports what is perhaps the most conspicuous change in the morphology of the alimentary tract under calorie restriction, which is the hypertrophy of the stomach observed in subjects.<ref>{{cite journal |last1=Yang |first1=Hyunwon |last2=Youm |first2=Yun-Hee |last3=Nakata |first3=Chiaki |last4=Dixit |first4=Vishwa Deep |title=Chronic caloric restriction induces forestomach hypertrophy with enhanced ghrelin levels during aging |journal=Peptides |date=October 2007 |volume=28 |issue=10 |pages=1931–1936 |doi=10.1016/j.peptides.2007.07.030}}</ref> || {{w|United States}} ({{w|Louisiana State University System}})
+| 2010 || 5,870 || 5,150 || 8,410 || 2,350 || 4,050
 |-
-| 2007 || Research || Longevity || || || Stydy by Speakman and Hambly calculates that if the lifespan effects observed in rodents translate faithfully to an effect in humans, then if a 48 year old engaged in 30% calorie restriction for 30 years, until the current mean life-expectancy of 78, they might expect to live only an extra 2.8 years because of the CR effect.<ref>{{cite journal |last1=Speakman |first1=John R. |last2=Hambly |first2=Catherine |title=Starving for Life: What Animal Studies Can and Cannot Tell Us about the Use of Caloric Restriction to Prolong Human Lifespan |journal=The Journal of Nutrition |date=2007-04-01 |volume=137 |issue=4 |pages=1078–1086 |doi=10.1093/jn/137.4.1078}}</ref> ||
+| 2012 || 7,620 || 9,170 || 10,900 || 2,820 || 5,240
 |-
-| 2007 || Research || Organ level effect (kidney) || || || Research by Chen et al. in rodents concludes that calorie restriction attenuates increased susceptibility to kidney injury in old subjects.<ref>{{cite journal |last1=Chen |first1=G. |last2=Bridenbaugh |first2=E. A. |last3=Akintola |first3=A. D. |last4=Catania |first4=J. M. |last5=Vaidya |first5=V. S. |last6=Bonventre |first6=J. V. |last7=Dearman |first7=A. C. |last8=Sampson |first8=H. W. |last9=Zawieja |first9=D. C. |last10=Burghardt |first10=R. C. |last11=Parrish |first11=A. R. |title=Increased susceptibility of aging kidney to ischemic injury: identification of candidate genes changed during aging, but corrected by caloric restriction |journal=American Journal of Physiology-Renal Physiology |date=October 2007 |volume=293 |issue=4 |pages=F1272–F1281 |doi=10.1152/ajprenal.00138.2007}}</ref> || {{w|United States}} ({{w|Texas A&M Health Science Center}})
+| 2014 || 9,190 || 7,660 || 12,800 || 3,120 || 6,690
 |-
-| 2008 || Research || Health (cancer) || || || Study by Wheatley et al. in mice suggests that although a low calorie diet does not induce weight loss, it may reduce {{w|colon cancer}} risk by lowering serum IGF-I levels.<ref>{{cite journal |last1=Wheatley |first1=Karrie E. |last2=Williams |first2=Elizabeth A. |last3=Smith |first3=Nicole C. P. |last4=Dillard |first4=Alice |last5=Park |first5=Eun Young |last6=Nunez |first6=Nomeli P. |last7=Hursting |first7=Stephen D. |last8=Lane |first8=Michelle A. |title=Low-Carbohydrate Diet Versus Caloric Restriction: Effects on Weight Loss, Hormones, and Colon Tumor Growth in Obese Mice |journal=Nutrition and Cancer |date=2007-12-28 |volume=60 |issue=1 |pages=61–68 |doi=10.1080/01635580701510150}}</ref> || {{w|United States}} ({{w|University of Texas at Austin}})
+| 2016 || 9,110 || 8,240 || 13,000 || 3,140 || 6,400
 |-
-| 2008 || Research || Organ level effect (bone) || || || Research by Baek et al. in rats concludes that moderate caloric restriction may cause bone loss at susceptible bone sites to a similar degree as does the unloading effect of microgravity in astronauts.<ref>{{cite journal |last1=Baek |first1=Kyunghwa |last2=Barlow |first2=Alicia A. |last3=Allen |first3=Matt R. |last4=Bloomfield |first4=Susan A. |title=Food restriction and simulated microgravity: effects on bone and serum leptin |journal=Journal of Applied Physiology |date=April 2008 |volume=104 |issue=4 |pages=1086–1093 |doi=10.1152/japplphysiol.01209.2007}}</ref> ||
+| 2017 || 9,590 || 8,870 || 13,500 || 3,880 || 6,910
 |-
-| 2008 || Research || Organ level effect (muscle) || || || Study by Colman et al. reports that calorie restriction has a protective effect against sarcopenic muscle loss in non-human primates.<ref>{{cite journal |last1=Colman |first1=R. J. |last2=Beasley |first2=T. M. |last3=Allison |first3=D. B. |last4=Weindruch |first4=R. |title=Attenuation of Sarcopenia by Dietary Restriction in Rhesus Monkeys |journal=The Journals of Gerontology Series A: Biological Sciences and Medical Sciences |date=2008-06-01 |volume=63 |issue=6 |pages=556–559 |doi=10.1093/gerona/63.6.556}}</ref> || {{w|United States}} (Wisconsin National Primate Research Center, {{w|University of Wisconsin-Madison}})
+| 2018 || 9,840 || 9,280 || 14,200 || 3,570 || 7,220
 |-
-| 2014 || Recommendation || || || || According to the [[w:National Institute for Health and Care Excellence|NICE]] 2014 guidelines, the routine use of {{w|very-low-calorie diet}}s is not recommended due to safety concerns, but this approach can be used under medical supervision if there is a clinical rationale for rapid weight loss in obese individuals, as part of a "multi-component weight management strategy" with continuous support and for a maximum of 12 weeks.<ref name="Overview {{!}} Obesit">{{cite web |title=Overview {{!}} Obesity: identification, assessment and management {{!}} Guidance {{!}} NICE |url=https://www.nice.org.uk/guidance/cg189 |website=www.nice.org.uk |access-date=24 June 2021}}</ref> ||
+| 2019 || 9,930 || 9,590 || 14,200 || 3,520 || 7,310
 |-
-| 2018 || Research || Health (brain) || || || Researchers find that {{w|caloric restriction}} increases lifespan but affects brain integrity in {{w|grey mouse lemur}} primates.<ref>{{cite journal |last1=Pifferi |first1=Fabien |last2=Terrien |first2=Jérémy |last3=Marchal |first3=Julia |last4=Dal-Pan |first4=Alexandre |last5=Djelti |first5=Fathia |last6=Hardy |first6=Isabelle |last7=Chahory |first7=Sabine |last8=Cordonnier |first8=Nathalie |last9=Desquilbet |first9=Loïc |last10=Hurion |first10=Murielle |last11=Zahariev |first11=Alexandre |last12=Chery |first12=Isabelle |last13=Zizzari |first13=Philippe |last14=Perret |first14=Martine |last15=Epelbaum |first15=Jacques |last16=Blanc |first16=Stéphane |last17=Picq |first17=Jean-Luc |last18=Dhenain |first18=Marc |last19=Aujard |first19=Fabienne |title=Caloric restriction increases lifespan but affects brain integrity in grey mouse lemur primates |journal=Communications Biology |date=December 2018 |volume=1 |issue=1 |pages=30 |doi=10.1038/s42003-018-0024-8}}</ref> || {{w|France}}
+| 2020 || 12,000 || 10,100 || 13,400 || 3,760 || 7,420
 |-
 |}
+[[File:Calorie restriction.png|thumb|center|700px]]
+=== Google Trends ===
+The chart below shows {{w|Google Trends}} data for Calorie restriction (search term), from January 2004 to June 2021, when the screenshot was taken. Interest is also ranked by country and displayed on world map <ref>{{cite web |title=Calorie restriction |url=https://trends.google.com/trends/explore?date=all&q=Calorie%20restriction |website=Google Trends |access-date=28 June 2021}}</ref>.
+[[File:Calorie restriction gt.png|thumb|center|600px]]
+=== Google Ngram Viewer ===
+The comparative chart below shows {{w|Google Ngram Viewer}} data for calorie restriction and caloric restriction, from 1900 to 2019.<ref>{{cite web |title=calorie restriction and caloric restriction |url=https://books.google.com/ngrams/graph?content=calorie+restriction%2C+caloric+restriction&year_start=1900&year_end=2019&corpus=26&smoothing=3&direct_url=t1%3B%2Ccalorie%20restriction%3B%2Cc0%3B.t1%3B%2Ccaloric%20restriction%3B%2Cc0#t1%3B%2Ccalorie%20restriction%3B%2Cc0%3B.t1%3B%2Ccaloric%20restriction%3B%2Cc0 |website=books.google.com |access-date=28 June 2021 |language=en}}</ref>
+[[File:Calorie restriction ngram.png|thumb|center|700px]]
+=== Wikipedia Views ===
+The chart below shows pageviews of the English Wikipedia article {{w|Calorie restriction}}, from July 2015 to May 2021.<ref>{{cite web |title=Calorie restriction |url=https://wikipediaviews.org/displayviewsformultiplemonths.php?page=Calorie+restriction&allmonths=allmonths-api&language=en&drilldown=all |website=wikipediaviews.org |access-date=28 June 2021}}</ref>
+[[File:Calorie restriction wv.png|thumb|center|550px]]
 ==Meta information on the timeline==
@@ Line 303: / Line 308: @@
 ===What the timeline is still missing===
-[https://sci-hub.do/10.1016/j.mam.2011.07.001]
+* {{w|Minnesota Starvation Experiment}}
-[https://sci-hub.do/10.1002/jemt.10214]
+* {{w|Fluid restriction diet}}
-[https://sci-hub.do/10.3181/00379727-183-42422]
+* Maybe more on how intermittent fasting and calorie restriction relate?
-[https://sci-hub.do/10.1007/978-3-319-42118-6_12]
+* Relationship between calorie restriction and hormesis
-[https://sci-hub.do/10.1016/j.mad.2005.03.012]
+* [https://sci-hub.do/10.1016/j.mam.2011.07.001]
-[https://sci-hub.do/10.1016/j.bbagen.2009.02.011]
+* [https://sci-hub.do/10.1002/jemt.10214]
-[https://sci-hub.do/10.1525/hsns.2010.40.1.79]
+* [https://sci-hub.do/10.3181/00379727-183-42422]
-[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2884327/]
+* [https://sci-hub.do/10.1007/978-3-319-42118-6_12]
-[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2884327/]
+* [https://sci-hub.do/10.1016/j.mad.2005.03.012]
-[http://sageke.sciencemag.org/cgi/content/full/sageke;2003/8/re2]
+* [https://sci-hub.do/10.1016/j.bbagen.2009.02.011]
-[https://www.jstor.org/stable/2640568?seq=1]
+* [https://sci-hub.do/10.1525/hsns.2010.40.1.79]
-[https://books.google.com.ar/books?id=yiLLDwAAQBAJ&pg=PA332&lpg=PA332&dq=%22Calorie+restriction%22+%22in+1900..1930%22&source=bl&ots=coo2beRkij&sig=ACfU3U3QyXTPsJPs368LK6kiqEQZdj3OCA&hl=en&sa=X&ved=2ahUKEwjo68y4r5XoAhVGHbkGHcQRD2EQ6AEwCnoECAgQAQ#v=onepage&q=%22Calorie%20restriction%22%20%22in%201900..1930%22&f=false]
+* [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2884327/]
-[https://books.google.com.ar/books?id=zWgEkmHwjo8C&pg=PA4&lpg=PA4&dq=%22Calorie+restriction%22+%22in+1900..1930%22&source=bl&ots=vldtO4AGUn&sig=ACfU3U1uZ05sGxTWAJ6_oV4JjgEO_sxvJw&hl=en&sa=X&ved=2ahUKEwjo68y4r5XoAhVGHbkGHcQRD2EQ6AEwC3oECA0QAQ#v=onepage&q=%22Calorie%20restriction%22%20%22in%201900..1930%22&f=false]
+* [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2884327/]
-[https://www.jstage.jst.go.jp/article/jnsv1973/47/1/47_1_13/_article])
+* [http://sageke.sciencemag.org/cgi/content/full/sageke;2003/8/re2]
-[https://books.google.com.ar/books?id=BIQSDAAAQBAJ&pg=PA43&lpg=PA43&dq=%22Calorie+restriction%22+%22in+1900..1930%22&source=bl&ots=3yJS1DbDia&sig=ACfU3U03vLLH2nuTz-jzZxlO0HWnbSPPIQ&hl=en&sa=X&ved=2ahUKEwjo68y4r5XoAhVGHbkGHcQRD2EQ6AEwD3oECAsQAQ#v=onepage&q=%22Calorie%20restriction%22%20%22in%201900..1930%22&f=false]
+* [https://www.jstor.org/stable/2640568?seq=1]
+* [https://books.google.com.ar/books?id=yiLLDwAAQBAJ&pg=PA332&lpg=PA332&dq=%22Calorie+restriction%22+%22in+1900..1930%22&source=bl&ots=coo2beRkij&sig=ACfU3U3QyXTPsJPs368LK6kiqEQZdj3OCA&hl=en&sa=X&ved=2ahUKEwjo68y4r5XoAhVGHbkGHcQRD2EQ6AEwCnoECAgQAQ#v=onepage&q=%22Calorie%20restriction%22%20%22in%201900..1930%22&f=false]
+* [https://books.google.com.ar/books?id=zWgEkmHwjo8C&pg=PA4&lpg=PA4&dq=%22Calorie+restriction%22+%22in+1900..1930%22&source=bl&ots=vldtO4AGUn&sig=ACfU3U1uZ05sGxTWAJ6_oV4JjgEO_sxvJw&hl=en&sa=X&ved=2ahUKEwjo68y4r5XoAhVGHbkGHcQRD2EQ6AEwC3oECA0QAQ#v=onepage&q=%22Calorie%20restriction%22%20%22in%201900..1930%22&f=false]
+* [https://www.jstage.jst.go.jp/article/jnsv1973/47/1/47_1_13/_article])
+* [https://books.google.com.ar/books?id=BIQSDAAAQBAJ&pg=PA43&lpg=PA43&dq=%22Calorie+restriction%22+%22in+1900..1930%22&source=bl&ots=3yJS1DbDia&sig=ACfU3U03vLLH2nuTz-jzZxlO0HWnbSPPIQ&hl=en&sa=X&ved=2ahUKEwjo68y4r5XoAhVGHbkGHcQRD2EQ6AEwD3oECAsQAQ#v=onepage&q=%22Calorie%20restriction%22%20%22in%201900..1930%22&f=false]
 {{w|Category:Diets}}
@@ Line 324: / Line 333: @@
 ==See also==
+* [[Timeline of weight loss]]
+* [[Timeline of fats]]
 * [[Timeline of senescence research]]
 * [[Timeline of malnutrition]]