Timeline of senescence research

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This page is a timeline of senescence research, including major theories, breakthroughs and organizations. "Senescence" here refers to "Ageing" rather than the phenomena of cellular senescence, which is a change in cell state associated with ageing, cancer prevention, wound healing, regeneration and embryonic/placenta development.

Big picture

Year/period Event
Ancient Greece Early speculations on aging are focussed on the bodily humoral imbalance and on the gradual loss of inner heat.[1]
Middle Age/Renaissance Rejuvenating or stopping the aging process is a major concern in this period.[1]
Renaissance–18th century Some themes around which aging and senescence research revolve are the idea that senescence is itself an illness, the image of the aged body as a lamp in which life-fuel has run out, the character alterations of elders, and the attempt to prolong life through specific diet or by substituting damaged body parts.[1]
Late 19th–20th century Starting from the so-called "fin-de-siècle" period, scientific optimism flourishes, and life-extensionism represents the most radical form of the trend.[2] Life expectancy starts to rise in the Western world.[3]
20th century "Since the 1930s, it has been found that restricting calories can extend lifespan in laboratory animals"[4] Modern anti-aging organizations merge and their proliferation multiplies toward the 2000s.[2] " The 1950s saw the first attempts to distinguish, measure and compare the functional and chronological ages of individuals, of which biological considerations were an important component"[5] The beginning of the term “senescence” in the context of mammalian cell cultures begins in the 1960s with the work of Hayflick and Moorhead.[6] In the 1980s, the field of life-span psychology is born.[7]

Visual and numerical data

Mentions on Google Scholar

The table below summarizes per-year mentions of senescence–related topics (entries without quotation marks) on Google Scholar as of month day, 2021.

Year Senescence Aging Longevity Life extension
1980 2,840 24,300 7,200 48,900
1985 3,760 36,300 9,210 43,400
1990 5,840 69,200 13,400 101,000
1995 8,150 114,000 18,300 131,000
2000 12,200 237,000 33,600 269,000
2002 13,400 302,000 41,600 299,000
2004 16,600 403,000 51,300 296,000
2006 21,500 470,000 62,900 341,000
2008 26,800 481,000 74,500 364,000
2010 33,500 587,000 85,400 397,000
2012 43,500 712,000 109,000 409,000
2014 47,900 653,000 103,000 366,000
2016 47,200 466,000 88,800 298,000
2017 45,300 441,000 81,500 254,000
2018 43,800 297,000 74,600 194,000
2019 39,500 201,000 59,400 148,000
2020 34,800 130,000 44,200 103,000
Senescence research.png

Google Trends

The comparative chart below shows Google Trends data for Senescence (Topic), Cellular senescence (Topic) and Negligible senescence (Topic), from January 2004 to April 021, when the screenshot was taken. Interest is also ranked by country and displayed on world map.[8]

Senescence research gt.png

Google Ngram Viewer

The chart below shows Google Ngram Viewer data for Senescence research, from 1950 to 2019.[9]

Senescence research ngram.png

Wikipedia Views

The chart below shows pageviews of the English Wikipedia article Senescence, on desktop from December 2007, and on mobile-web, desktop-spider, mobile-web-spider and mobile app, from July 2015; to March 2021.[10]

Senescence wv.png

Full timeline

Year/period Type of Event Key topic Event Location
c. 99 BC – c. 55 BC Scientific development (theory) Roman poet and philosopher Lucretius argues that aging and death are beneficial because they make room for the next generation. This view will persist among biologists well into the 20th century.[11]
Lucretius1.png
5th century Scientific development (theory) Early formulations, described by Hippocrates' system of four humours, theorize old age as a consequence of the gradual consumption of the innate heat with the inevitable loss of body moisture.[1] Greece
Hippocrates.jpg
1825 Scientific development British mathematician Benjamin Gompertz proposes an exponential increase in death rates with age, giving birth to what later will be called The Gompertz-Makeham law.[12][13] United Kingdom
Gompertz.png
1882 German biologist August Weismann introduces the wear and tear theory of ageing, which sustains that cells and tissues have vital parts that wear out resulting in aging. "Like components of an aging car, parts of the body eventually wear out from repeated use, killing them and then the body."[4]
1891 Scientific development (theory) German evolutionary biologist August Weismann proposes the first formal programmed aging theory as an evolutionary explanation of aging driven by group selection. His argument is that aging evolved to the advantage of the species (e.g., by replacing worn out individuals with younger ones), not the individual.[14][15] Germany
August Weismann.jpg
1904 Scientific development (theory) Biological ageing theory Metchnikoff introduces the Autointoxication theory of ageing, which is considered important at the whole animal level.[16] This is one of the first toxic theories as Metchnikoffs proposes the idea of autointoxication by products of bacterial origin, primarily from bacterial processes in the large intestine. Metchnikoff believes that even simple changes of acidity by the consumption of yogurt could inhibit the production of bacterial toxins.[17]
1908 Scientific development (theory) Biological ageing theory (Rate-of-living theory) German physiologist Max Rubner describes his rate-of-living theory, which proposes that a slow metabolism increases an animal's longevity. It states that fast basal metabolic rate corresponds to short maximum life span.[18][19] Germany
Max Rubner.jpg
1928 Scientific development (theory) Biological ageing theory (rate of living hypothesis American biologist Raymond Pearl describes the rate of living hypothesis as an expansion of the earlier theory by Max Rubner. It states that organisms with a high metabolic rate have shorter lives.[20] United States
Dr. Raymond Pearl, Food. Adm. LCCN2016824384 (cropped).jpg
1934 Scientific development Calorie restriction Mary Crowell and Clive McCay at Cornell University discover that calorie restriction can extend lifespan twofold in rats.[21] United States
1939 Organization (non-profit) Ageing The British Society for Research on Ageing is founded by Russian-British gerontologist Vladimir Korenchevsky.[22] It promotes research to understand the causes and effects of the ageing process.[23] United Kingdom
1940 Ageing theory Nagorny introduces a theory of ageing based on age changes, which is described as the stabilization and inactivation (insolubilization) of intercellular structural proteins. Nagorny postulates that ageing is linked to the accumulation of intercellular inactivated "metaplasmic" proteins due to the inability of enzymes to destroy them.[17]
1942 Scientific development Ageing theory (cross-linking theory of aging) Johan Björkstein proposes the cross‐linkage theory of aging. According to it, aging results from the accumulation of intra‐ and intermolecular covalent bonds between molecules, termed “cross‐links.”[24][4]
1945 Scientific development The idea that free radicals are toxic agents is first proposed by Rebeca Gerschman and colleagues.[25]
1945–1949 Scientific development The advent of molecular biology changes the theoretical perception of aging dramatically, as the precise molecular structure of proteins and genetic material becomes known.[2] United States
1947 Scientific development Ageing theory Bogomolets links ageing with the functional deterioration of connective tissues.[17]
1952 Scientific development Ageing theory (Mutation accumulation) British biologist Peter Medawar formulates the first modern theory of mammal aging, known as mutation accumulation, whereby the mechanism of action involves random, detrimental germline mutations of a kind that happen to show their effect only late in life.[11]
Peter Brian Medawar.jpg
1954 Ageing theory The free radicals theory is first introduced by Dr. Gerschman. Later developed by Dr. Denham Harman, this theory proposes that superoxide and other free radicals cause damage to the macromolecular components of the cell, giving rise to accumulated damage causing cells, and eventually organs, to stop functioning.[4]
1954 Research by Nikitin introduces a theory of ageing based on age changes, and described as the accumulation of protein-DNA cross-links and progressive stabilization of chromatin complexes. This theory is further elaborated by von Hahn.[17]
1956 Scientific development (theory) Free radical theory of aging American chemist Denham Harman presents the free radical theory of aging, which states that organisms age over time due to the accumulation of damage from free radicals in the body.[20] Harman is known as the "father of the free radical theory of aging".[26][27] United States
1956 Benefitted by the cosolidation of knowledge of the toxic intermediate products of normal metabolism, Vladimir Korenchevsky introduces a general toxic theory of ageing.[17]
1957 Scientific development (theory) Biological ageing theory (Antagonistic pleiotropy hypothesis) American evolutionary biologist George C. Williams proposes the today called Antagonistic pleiotropy hypothesis (AP) for the evolution of aging. It occurs when one gene controls for more than one phenotypic trait where at least one of these is beneficial to the organism's fitness and at least one is detrimental, thus accumulating damage.[11][28] United States
1957 Scientific development Biological ageing theory M. F. Sinex publishes article titled Aging and the lability of irreplacable molecules, establishing a theory based on quantitative changes of proteins, and describing as the loss of irreplaceable molecules or enzymes.[17][29]
1958 Scientific development (theory) Somatic mutation theory American physicists Gioacchino Failla and Leo Szilard propose the somatic mutation theory, which suggests that aging is caused by random DNA damage in somatic cells and that the extent of damage is enhanced by radiation.[2] United States
1958 Scientific development (clinical research program) Baltimore Longitudinal Study of Aging The Baltimore Longitudinal Study of Aging begins in the United States as a clinical research program on human aging. As of 2020, it is the longest-running study of aging in that country. "Volunteers of different ages join the study when they are healthy, and have follow-up visits for life. Visits last for multiple days. Participants are evaluated for many physical elements as well as for brain function. Physical tests are given. Information on mood, personality, and social aspects of life is also collected. This program has contributed more than any other research project to our understanding of aging."[30] United States
1959 Scientific development Biological ageing theory Sacher introduces a size-lifespan correlation theory, positively correlating body weight with the longevity in mammals.[17]
1961 Scientific development Senescence The beginning of the term “senescence” in the context of mammalian cell cultures is considered to be born out of the discovery by American anatomist Leonard Hayflick and his colleague Paul Moorhead, who describe that primary cells have a finite lifespan when cultured in vitro, contrasting cancer cells that divide without limits.[6] Hayflick demonstrates that a population of normal human fetal cells in a cell culture will divide between 40 and 60 times before entering a senescence phase. This process will be known later as the Hayflick limit.[31][32][33] United States
1961 Scientific development Ageing theory Vladimir Korenchevsky introduces the Endocrine theory og ageing, which is considered a major theory at the organ level.[16]
1962 Scientific development Ageing theory Romanian scientists Constantin Ion Parhon and Simion Oeriu introduce a theory of ageing based on age changes, and described as the progressive demethylation of proteins.[17] Romania
1963 Scientific development Ageing theory Leslie Orgel proposes the Error Catastrophe Theory of Aging.[17]
1963 Scientific development Caenorhabditis elegans South African biologist Sydney Brenner suggests the ability to easily and cheaply grow large quantities of worms in the lab as being very helpful for aging research, especially when identifying long-lived mutants caenorhabditis elegans, which have a relatively short lifespan (average approximately 17 days at 20 °C), and the lifespan is largely invariant.[34]
1964 Scientific development Ageing theory Romanian biochemist Simion Oeriu introduces a theory of ageing based on age changes, described as accumulation of -S-S, inter- and intra- molecular bonds.[17] Romania
1965 Ageing theory Leonard Hayflick describes cell senescence as the process that limits the number of cell divisions normal human cells can undergo in culture. This work formulates the The Cellular Senescence Theory of aging.[35][36]
1965–1969 Scientific development DNA methylation The strong effect of age on DNA methylation levels is discovered,[37] thus rendering it an accurate biological clock in humans and chimpanzees.[38]
1966 Sacher introduces the Wear and tear theory of ageing, which is considered an important theory at the whole animal level.[16]
1967 Scientific development (theory) DNA damage theory ofeleg aging C. Alexander sets the grounds of the DNA damage theory of aging by suggesting that DNA damage, as distinct from mutation, is the primary cause of aging.[39] This theory becomes stronger through further experimental support during the following decades.[40][41]
1969 Publication Immunologic Theory of Aging American physician Roy Walford publishes the Immunologic Theory of Aging, contributing to the basis for many current ideas about immunological aging.[42] This is considered a major theory at the organ level.[16] United States
1970 Scientific development Ageing theory Selye introduces the Stress damage theory, which is considered an important theory of ageing at the whole animal level.[16]
1970 Organization American Aging Association The American Aging Association is founded by Denham Harman.[43] United States
1974 Organization National Institute on Aging The National Institute on Aging (NIA) is formed as a division of the United States National Institutes of Health (NIH), with the purpose of conducting research on aging process and age-related diseases and disseminating information on health and research advances, among other aims.[44][45] United States (National Institute on Aging)
1974 Scientific development Ageing theory Study by Arthur B. Robinson introduces a theory of ageing based on age changes, and described as the progressive deamination of glutaminyl and asparaginyl residues in proteins.[46][17] United States
1975 Sacher introduces a brain size–lifespan correlation theory, suggesting that larger brains make evolutionary selection of longer lifespan necessary.[17]
1975 Scientific development Telomerase Australian-American molecular biologist Elizabeth Blackburn discovers the unusual nature of telomeres, with their simple repeated DNA sequences composing chromosome ends.[47][48] Some years later, Blackburn, Carol Greider and Jack Szostak discover how chromosomes are protected by telomeres and the enzyme telomerase, for which they receive the 2009 Nobel Prize in Physiology or Medicine.[49] Further experiments establish the role of telomere shortening in cellular aging and telomerase reactivation in cell immortalization.[50] United States
1976 Scientific development Ageing theory Cutler introduces a theory of ageing based on age changes, and described as the cross-links between DNA molecules.[17]
1977 Scientific development Ageing theory English biologist Thomas Kirkwood proposes the third mainstream theory of ageing, the disposable soma, which states that organisms only have a limited amount of energy that has to be divided between reproductive activities and the maintenance of the non-reproductive aspects of the organism.[51]
1977 Research started by Kirkwood establishes an aging theory on lifespan correlations with changes at the molecular level. This theory suggests that immortal germ cells may have more comprehensive repairs and may have higher accuracy of synthesis than somatic cells.[17]
1977 Scientific development Ageing theory Holliday et al. introduce the commitment theory of cellular ageing, which stipulates the existence of a biological clock (pace-maker).[17]
1977 Scientific development Caenorhabditis elegans Klass publishes that C. elegans is a good system for aging studies as he establishes a method to consistently measure lifespan, concluding that this could lead to future detailed analysis combining genetics and biochemistry. Klass also finds that altering either temperature or the amount of food results in a change in lifespan. In addition, only small effects on lifespan are observed based on parental age or parental lifespan.[34]
1977 Biological ageing theory (Disposable soma theory) British biologist Thomas Kirkwood first proposes the disposable soma theory of aging in a Nature review article. This theory is inspired by Leslie Orgel's Error Catastrophe Theory of Aging.[52]
1978 Todd introduces a size-lifespan correlation theory, positively correlating size, height and longevity among tree species. He suggests a protective role of large sizes from disease, predators, etc.[17]
1978 Scientific development (theory) Mitochondrial theory of aging Soviet scientist A. N. Lobachev proposes the mitochondrial non free radical theory of aging, which suggests that the main reason of accumulation of damages in mt DNA is the fact that at certain moment of cell life, the development of mitochondria begin to conflict with the development of nucleus. This theory concludes that mitochondria appears to be the «biologic clock» of the cell and programm the duration of its life.[53][54] Russia
1978 Scientific development Caenorhabditis elegans "For research on aging, early studies in C. elegans focused on the feasibility of measuring lifespan and the use of 5-Fluoro-2′-deoxyuridine (FUDR) to maintain synchronous cultures of aged animals (Hosono 1978a, 1978b)."[34]
1979 Scientific development Research by D. Gershon at Technion introduces a theory of ageing based on age changes, and described as age-altered enzymes theory (age-related accumulation of conformational changes in protein leading to the inactivation of enzymes).[17] Israel
1979 Kirkwood and Holliday introduce a theory correlating lifespan with changes at the molecular level. Their hypothesis suggests higher fidelity of syntheses of macromolecules in longer-lived species and cellular clones.[17]
1980 M. S. Kanungo introduces a theory of ageing based on age changes, describing it as the decrease of phosphorylation and acetylation of chromatin proteins as the cause of defects and decline in transcription.[17][55]
1980 "An interesting classification was suggested by Strehler (1980), who grouped theories of ageing into evolutionary (selection for limited lifespan), post-reproductive failure, failure of coordinating systems, pleiotropic side effects of advantageous qualities (clonal ageing, autoimmunity), informational failure (changes in proteins and DNA), structural damage or loss and accumulation of dysfunctional materials (age-pigments, inactive proteins, lytic enzymes, etc.) This classification underlines the interrelation between different mechanisms and it tries to unite all these types into two ‘ supergroups ’ - genetically programmed ageing, and ageing secondary to genetic qualities (entropic increase)."[17]
1982 Pashko and Schwartz propose an aging theory on lifespan correlations at the cellular level, suggesting a correlation between lifespan and species-specific activity of detoxification enzymes (longer-lived animals have higher efficiency of detoxification and are more resistant to environmental toxins).[17]
1986 Organization (non-profit) Alliance for Aging Research The Alliance for Aging Research is founded a non-profit organization, with the purpose to promote medical and behavioral research into the aging process.[56] United States
1987 Scientific development Cell death B M Stanulis-Praeger determines cell death to be a primary consequence of senescence.[57]
1988 Scientific development Caenorhabditis elegans Genetic work by Tom Johnson et al. on mutant C. elegans mapps all of them to a single genetic locus, named age-1. This is the first breakthrough in aging research for studies based on C. elegans as this study reveals that it is possible to identify mutants that altered lifespan and more importantly, individual genes can modulate lifespan.[34]
1989 The network theory of aging is introduced.[58]
1990 Z. A. Medvedev publishes review stating that there are more than 300 theories of ageing and the number is increasing.[17]
1990-1995 Scientific development Negligible senescence The term negligible senescence is first used by professor Caleb Finch to describe organisms such as lobsters and hydras, which do not show symptoms of aging.[59]
1991 Scientific development (theory) Reliabity theory of aging Leonid A. Gavrilov and Natalia S. Gavrilova apply the principles of reliability theory to human biology, proposing a reliabity theory of aging which is based on the premise that humans are born in a highly defective state. According to the model, this is then made worse by environmental and mutational damage, and survival of the organism depends on redundancy.[60][61]
1991 Scientific development Cell death Leonard Hayflick describes an increase in cell degeneration and debris, resembling cell death.[6] United States
1993 Scientific development Caenorhabditis elegans American molecular biologist Cynthia Kenyon discovers that a single-gene mutation (Daf-2) can double the lifespan of nematode Caenorhabditis elegans and that this can be reversed by a second mutation in daf-16m.[62][63] United States
Cyntia Kenyon 01.JPG
1994 Literature Biological age Leonard Hayflick publishes How and Why we Age, which elaborates on the difference between biological and chronological age and then explores on how understanding of aging has changed through history.[64]
1995 Scientific development senescent cell Detection of senescent cells using a cytochemical assay is first described.[65] Researchers discover that senescent cells express a β-galactosidase activity; and describe the “senescence-associated β galactosidase” (SA-βgal) biomarker, which conveniently identifies individual senescent cells in vitro and in vivo.[66]
1995 The existence of senescence-associated beta-galactosidase is proposed by Dimri et al.[67] following the observation that when beta-galactosidase assays were carried out at pH 6.0, only cells in senescence state develop staining. They proposed a cytochemical assay based on production of a blue-dyed precipitate that results from the cleavage of the chromogenic substrate X-Gal, which stains blue when cleaved by galactosidase. Since then, even more specific quantitative assays were developed for its detection at pH 6.0.[68][69][70]
1995 Scientific development The remodeling theory of aging is introduced.[58]
1995 Scientific development Cell death Scientific development by E. Wang shows that cellular senescence is associated with a reduced sensitivity to cell death.[6][71]
1997 (August 7) Supercentenarian French supercentenarian Jeanne Calment dies at the age of 122 years and 164 days, being the oldest human whose age is well-documented. France
1999 Organization (research institute) Buck Institute for Research on Aging The Buck Institute for Research on Aging is established as an independent biomedical research institute devoted solely to research on aging and age-related diseases.[72][73] United States
Buck logo tagline period.png
1999 Literature Engineered negligible senescence Aubrey de Grey publishes The Mitochondrial Free Radical Theory of Aging, which introduces the term "engineered negligible senescence".[74]
2006 Organization (research network) Network Aging Research Network Aging Research (Netzwerk Alternsforschung) is founded at Heidelberg University.[75] Germany
2009 Scientific development Rapamycin Ahe group of three laboratories initiate a study of the effects of rapamycin on the life span of mice. After administering the agent at late ages, the team discovers a significant increase in maximum life span.[27]
2009 Telomerase Elizabeth Blackburn, Carol Greider, and Jack Szostak are awarded the Nobel Prize in Physiology or Medicine "for the discovery of how chromosomes are protected by telomeres and the enzyme telomerase."[76] These researchers are aware of the implications of their research on telomerase for the biology of aging, in particular Carol Greider who would become quite active in that field.[27]
Nobel Prize 2009-Press Conference Physiology or Medicine-04.jpg
2010 Scientific development Telomerase Harvard scientists reverse aging process in mice through reactivation of telomerase.[77] United States
2010 Organization (research network) European Network in Aging Studies The European Network in Aging Studies is established.[78][79] Europe
2012 Scientific development Researchers from the Institute of Molecular Oncology (IFOM) in Milan and Molecular Genetics of the National Research Council (IGM-CNR) in Pavia identify for the first time a class of non-coding RNAs, called “DNA Damage Response RNAs (DDRNAs)”, laying the foundation for the future advances in cellular aging.[80] Italy
2012 Scientific development Scientific development by Nelson et al. shows that the bystander effect of senescent cells negatively affects non‐senescent cells via reactive oxygen species (ROS). The researchers also show that a paracrine effect of senescent cells can damage DNA.[6][81]
2013 (January) Organization Senior welfare The North American Network in Aging Studies (NANAS) is established with the ultimate purpose to improve the health, care, and quality of life for people aging into old age.[78] United States
2013 Scientific development Senescence A group of scientists define nine hallmarks of aging that are common between organisms with emphasis on mammals:
2016 Scientific development Mitochondrial theory of ageing Scientists at Newcastle University demonstrate for the first time that mitochondria are major triggers of cell aging, after having found that when mitochondria are eliminated from aging cells, the latter become much more similar to younger cells. This discovery advances a step closer to developing therapies to counteract the aging of cells, by targeting mitochondria.[83][84][85] United Kingdom (Newcastle University)
2017 (December) Scientific development Protein expression Study shows that preventing wrinkles could be as easy as expressing a protein called FKBP1b.[86]
2018 (January) Scientific development Researchers at the University of Texas Health Science Center (UTHealth) in Houston report a connection between accelerated epigenetic aging and bipolar disorder. The results could explain why people suffering from bipolar disorder are more likely to die from age-related diseases.[87] United States
2018 Scientific development Negligible senescence Researchers identify naked mole-rats as the first mammal to defy the Gompertz–Makeham law of mortality, and achieve negligible senescence. It would be speculated however that this may be simply a "time-stretching" effect primarily due to their very slow (and cold-blooded and hypoxic) metabolism.[88][89]
Nacktmull.jpg
2019 Scientific development Researchers show that many major features of cellular senescence, such as the pro‐inflammatory phenotype, are dependent on the stable cell cycle arrest.[90][6]
2019 Scientific development Telomerase Scientists manage to extend the average lifespan of mice by breeding them using embryonic stem cells with extra-long telomeres. The finding is significant as no genetic modification is conducted.[91][92][93]
2019 (December 9) Scientific development Premature ageing Researchers at the Pasteur Institute identify the CSB protein, whose absence or dysfunction causes early ageing, among other afflictions, in patients with Cockayne syndrome.[94] France
2020 (July) Scientific development Scientists, using public biological data on 1.75 million people with known lifespans overall, identify 10 genomic loci which appear to intrinsically influence healthspan, lifespan, and longevity – of which half have not been reported previously at genome-wide significance and most being associated with cardiovascular disease – and identify haem metabolism as a promising candidate for further research within the field. Their study suggests that high levels of iron in the blood likely reduce, and genes involved in metabolising iron likely increase healthy years of life in humans.[95] United Kingdom

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See also

External links

References

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Category:Senescence Category:Medicine timelines