Difference between revisions of "Timeline of senescence research"

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.

|Ancient Greece || Early speculations on aging are focussed on the bodily [[Humorism|humoral]] imbalance and on the gradual loss of inner heat.<ref name=history-of-research/>

|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.<ref name=ilia-stambler>{{cite book |date=2014 |title=A History of Life-Extensionism In The Twentieth Century |url= |location=Rison Lezion, Israel |publisher=Longevity History |page= |isbn=1500818577}}</ref> Life expectancy starts to rise in the Western world.<ref>{{cite web |url=https://ourworldindata.org/life-expectancy/ |title=Life Expectancy}}</ref>

|20th century || Senescence research focuses on four major directions: [[cell theory|cellular theories]], immune-metabolic models,  evolutionary explanations and [[molecular biology]]-based approaches.<ref name=history-of-research/>

| c. 99 BC – c. 55 BC|| 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.<ref name=the-evolution-of-aging>{{cite magazine |author1=Daniel Fabian |author2=Thomas Flatt |title=The Evolution of Aging |url=http://www.nature.com/scitable/knowledge/library/the-evolution-of-aging-23651151 |magazine=Nature |location= |publisher= |date= |access-date= }}</ref> ||

|5th century || Theory ||Early formulations, described by  [[Hippocrates]]' system of four [[Humorism|humours]], theorize old age as a consequence of the gradual consumption of the innate heat with the inevitable loss of body moisture.<ref name=history-of-research/>  || Greece

|1825 || Development || [[Benjamin Gompertz]] proposes an exponential increase in death rates with age, giving birth to what later will be called The [[Gompertz-Makeham law of mortality|Gompertz-Makeham law]] <ref>{{cite DNB|wstitle=Gompertz, Benjamin}}</ref><ref>{{cite journal |last=Gompertz |first=B. |year=1825 |title=On the Nature of the Function Expressive of the Law of Human Mortality, and on a New Mode of Determining the Value of Life Contingencies |journal=Philosophical Transactions of the Royal Society |volume=115 |issue= |pages=513–585 |id= |url=http://visualiseur.bnf.fr/Visualiseur?Destination=Gallica&O=NUMM-55920 |doi=10.1098/rstl.1825.0026}}

| 1891 || Theory || [[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.<ref>{{cite web|url=http://www.programmed-aging.org/programmed_aging_theory_FAQ.html|title=Biological Aging Theory - Frequently asked Questions and Answers}}</ref><ref>{{cite web |title=A Weismann| URL=http://www.senescence.info/evolution_of_aging.html}}</ref> ||

|1908|| Theory || [[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.<ref>{{cite journal |author1=Michael Ristow |author2=Kathrin Schmeisser |date= |title=Mitohormesis: Promoting Health and Lifespan by Increased Levels of Reactive Oxygen Species (ROS) |journal= Dose Response|publisher= |volume= 12|issue= |pages= 288–341|doi= 10.2203/dose-response.13-035.Ristow|pmc=4036400 |pmid= 24910588 |year=2014}}</ref><ref>Rubner, M. (1908). Das Problem det Lebensdaur und seiner beziehunger zum Wachstum und Ernarnhung. Munich: Oldenberg.</ref> ||  

|1913 ||Organization|| The [[Life Extension Institute]] is inaugurated as a longevity research center, with US president [[William Howard Taft]] as chairman.<ref>{{cite book|last1=Hamowy|first1=Ronald|title=Government and Public Health in America|url=https://books.google.com.ar/books?id=TSn0SVM3GRcC&pg=PA430&lpg=PA430&dq=%221913%22+%22+Life+Extension+Institute+%22&source=bl&ots=OQ1ROt5qc8&sig=q-RR0XyiQ2phecDuQWf581q6RxY&hl=es&sa=X&ved=0ahUKEwikvIOn9oXRAhWPPpAKHURcBUQQ6AEIPjAD#v=onepage&q=%221913%22%20%22%20Life%20Extension%20Institute%20%22&f=false|accessdate=21 December 2016}}</ref><ref name=ilia-stambler/>||U.S.A.

| 1928 || Theory || [[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.<ref name=oxidative-stress>{{cite book |author= David Costantini |title=Oxidative Stress and Hormesis in Evolutionary Ecology and Physiology |url=https://books.google.com.ar/books?id=rTe8BAAAQBAJ&pg=PA306&dq=Rate+Of+Living+Hypothesis&hl=es&sa=X&ved=0ahUKEwjui-iU5tDMAhXJIJAKHe4lBSMQ6AEILDAC#v=onepage&q=Pearl&f=false |location= |publisher= |page=306 |date= |isbn=}}</ref>||

| 1934 || Discovery || Mary Crowell and Clive McCay of Cornell University discover that [[calorie restriction]] can extend lifespan twofold in rats.<ref>{{cite book |last= Fossel |first=Michael |date= |title=The Telomerase Revolution: The Enzyme That Holds the Key to Human Aging |url= |location= |publisher= |page= |isbn=}}</ref>||

|1945–1949|| 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.<ref name=ilia-stambler/> || U.S.A.

|1950s || Theory ||  [[Denham Harman]] presents his ''[[free radical theory of aging]]'', which states that organisms age over time due to the accumulation of damage from free radicals in the body.<ref name=oxidative-stress/>||

| 1952 || Theory || [[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.<ref name=the-evolution-of-aging/> ||

| 1957 || Theory|| [[George C. Williams (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.<ref name=the-evolution-of-aging/><ref name="williams">{{cite journal|doi=10.2307/2406060 |author=Williams, G.C.|title=Pleiotropy, natural selection and the evolution of senescence|journal=Evolution|volume=11|issue=4|pages=398–411 |year=1957|format=PDF|url=http://www.telomere.org/Downloads/Williams_searchable.pdf|jstor=2406060}} Paper in which Williams describes his theory of antagonistic pleiotropy.</ref> ||

|1958 || Theory || [[Gioacchino Failla|G. Failla]] and [[Leó Szilárd]] 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.<ref name=ilia-stambler/> ||

|1961 || Theory || American anatomist [[Leonard 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]].<ref>{{cite web|url=http://science.howstuffworks.com/life/genetic/hayflick-limit.htm|title=Will the Hayflick limit keep us from living forever?}}</ref><ref name="pmid13905659">{{cite journal |vauthors=Hayflick L, Moorhead PS |title=The serial cultivation of human diploid cell strains |journal=Exp Cell Res |volume=25 |pages=585–621 |year=1961 |pmid=13905658 |doi=10.1016/0014-4827(61)90192-6 |issue=3}}</ref><ref>{{cite journal |author=Hayflick L. |title= The limited in vitro lifetime of human diploid cell strains |journal=Exp. Cell Res. |year=1965 |volume=37 |issue=3 |pages=614–636 |pmid= 14315085 |doi=10.1016/0014-4827(65)90211-9}}</ref>||[[Wistar Institute|Philadelphia]]  

|1965–1969|| Discovery || The strong effect of age on [[DNA methylation]] levels is discovered,<ref>{{cite journal | last1 = Berdyshev | first1 = G | last2 = Korotaev | first2 = G | last3 = Boiarskikh | first3 = G | last4 = Vaniushin | first4 = B | year = 1967 | title = Nucleotide composition of DNA and RNA from somatic tissues of humpback and its changes during spawning | url = | journal = Biokhimiia | volume = 31 | issue = | pages = 88–993 }}</ref> thus rendering it an accurate biological clock in humans and chimpanzees.<ref>{{Cite journal |author=Horvath S |title=DNA methylation age of human tissues and cell types |journal=Genome Biology |volume=14 |number=R115 |pages= R115|year=2013 |url=http://genomebiology.com/2013/14/10/r115|doi=10.1186/gb-2013-14-10-r115|pmid=24138928 |pmc=4015143}}</ref> ||

|1967 || Theory || 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.<ref>{{cite journal |author=Alexander P |title=The role of DNA lesions in the processes leading to aging in mice |journal=Symp. Soc. Exp. Biol. |volume=21 |pages=29–50 |year=1967 |pmid=4860956 }}</ref> This theory becomes stronger through further experimental support during the following decades.<ref>{{cite book |vauthors=Bernstein C, Bernstein H |title=Aging, Sex, and DNA Repair |publisher=Academic Press |location=San Diego CA |year=1991 |isbn=0123960037 }}</ref><ref>{{cite journal |vauthors=Ames BN, Gold LS |title=Endogenous mutagens and the causes of aging and cancer |journal=Mutat. Res. |volume=250 |issue=1-2 |pages=3–16 |year=1991 |pmid=1944345 |doi=10.1016/0027-5107(91)90157-j}}</ref> ||

|1969||Book||American physician [[Roy Walford]] publishes ''The Immunologic Theory of Aging'', contributing to the basis for many current ideas about immunological aging.<ref>{{cite journal|title=Roy Walford and the immunologic theory of aging|doi=10.1186/1742-4933-2-7| pmc=1131916 | pmid=15850487|volume=2|year=2005|journal=Immun Ageing|pages=7|author=Effros RB}}</ref>||

|  1974 || Organization || The [[National Institute on Aging]] (NIA) is formed as a division of the U.S. [[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.<ref>{{cite book|last1=Ofahengaue Vakalahi|first1=Halaevalu F.|last2=Simpson|first2=Gaynell M.|last3=Giunta|first3=Nancy|title=The Collective Spirit of Aging Across Cultures|page=20|url=https://books.google.com.ar/books?id=58XEBAAAQBAJ&pg=PA20&lpg=PA20&dq=%221974%22+%22National+Institute+on+Aging+%22&source=bl&ots=h5rgitHiKf&sig=W29lqL0xqia6j_EdPOGrioIvd58&hl=en&sa=X&ved=0ahUKEwi6kuXq9oXRAhXLDJAKHYgwA-oQ6AEINzAF#v=onepage&q=%221974%22%20%22National%20Institute%20on%20Aging%20%22&f=false|accessdate=21 December 2016}}</ref><ref>{{cite web |url=https://www.nia.nih.gov/ |title=National Institute of Aging}}</ref> || [[Baltimore]], U.S.A.

| 1975–1984 ||Discovery || [[Elizabeth Blackburn]] discovers the unusual nature of telomeres, with their simple repeated DNA sequences composing chromosome ends.<ref>{{cite web|url=http://www.ibiology.org/ibioseminars/genetics-gene-regulation/elizabeth-blackburn-part-1.html|title=ELIZABETH BLACKBURN: TELOMERES AND TELOMERASE}}</ref><ref>{{cite journal |author=Blackburn AM |title=A tandemly repeated sequence at the termini of the extrachromosomal ribosomal RNA genes in Tetrahymena |journal=J. Mol. Biol. |volume=120 |issue=1 |pages=33–53 | date=March 1978 |doi=10.1016/0022-2836(78)90294-2 |pmid=642006 |first2=Joseph G.|last2=Gall }}</ref> 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.<ref>{{cite web|url=http://nobelprize.org/nobel_prizes/medicine/laureates/2009/press.html |title=The 2009 Nobel Prize in Physiology or Medicine - Press Release |publisher=Nobelprize.org |date=2009-10-05 |accessdate=2012-06-12}}</ref>  Further experiments establish the role of telomere shortening in [[cellular aging]] and telomerase reactivation in cell immortalization.<ref>{{cite news|title=Unravelling the secret of ageing |url=http://www.cosmosmagazine.com/features/unraveling-secret-ageing/ |work=COSMOS: The Science of Everything |date=October 5, 2009 |deadurl=yes |archiveurl=https://web.archive.org/web/20150114212810/http://cosmosmagazine.com/features/unraveling-secret-ageing/ |archivedate=January 14, 2015 }}</ref> ||

|1977 || Theory|| [[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.<ref>{{cite book |last=Goldsmith  |first=Theodore |date= |title=The Evolution of Aging: How New Theories Will Change the Future of Medicine |url=https://books.google.com.ar/books?id=bCwC22mim4gC&pg=PA48&lpg=PA48&dq=%22Thomas+Kirkwood%22+%22Disposable+soma%22+%221977%22&source=bl&ots=JCdSwbtSVo&sig=Ht8Ttjq7KF_zPMvlhtxPbY_ZxHc&hl=en&sa=X&ved=0ahUKEwi5uqfCmqjOAhXHvJAKHWIlBrwQ6AEIPTAG#v=onepage&q=%22Thomas%20Kirkwood%22%20%22Disposable%20soma%22%20%221977%22&f=false |location= |publisher= |page=48 |isbn=}}</ref>||

|1990 || Organization || The [[Gerontology Research Group ]](GRG) is founded as a global group of researchers in various fields that verifies and tracks supercentenarians. It also aims to further gerontology research with a goal of reversing or slowing aging.<ref>{{cite web |title=Keeping Track of the Oldest People in the World |url=http://www.smithsonianmag.com/science-nature/keeping-track-oldest-people-world-180951976/?no-ist |last=Nuwer |first=Rachel |publisher=Smithsonion.com |date=4 July 2014 |accessdate=3 January 2015}}</ref><ref>{{cite news |title=Supercentenarians giving researchers clues on longevity |url=http://articles.chicagotribune.com/2006-02-08/features/0602080100_1_guinness-world-records-oldest-people-supercentenarians |newspaper=Chicago Tribune |last=White |first=Gayle |agency=Cox News Service |date=8 February 2006 |accessdate=3 January 2015}}</ref> || [[Los Angeles]], ([[UCLA]])

|1990-1995 || Development || 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.<ref>{{cite book |author=Greg Critser |title=Eternity Soup: Inside the Quest to End Aging |url=https://books.google.com.ar/books?id=5ikIgPLoM7IC&pg=PT173&lpg=PT173&dq=The+term+negligible+senescence+is+first+used+by+professor+Caleb+Finch&source=bl&ots=8x928wNPqZ&sig=tsCM_DxFBQ-43HGdliqI1NsrsAs&hl=es&sa=X&ved=0ahUKEwjR6rLK79DMAhXCQpAKHfDdBKEQ6AEIOjAE#v=onepage&q=The%20term%20negligible%20senescence%20is%20first%20used%20by%20professor%20Caleb%20Finch&f=false |location= |publisher= |page= |date= |isbn=}}</ref> ||  

|1991 || Theory || [[Leonid A. Gavrilov]] and Natalia S. Gavrilova apply the principles of [[reliability theory]] to human biology, proposing a ''[[Reliability theory of aging and longevity|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 (engineering)|redundancy]].<ref>{{cite magazine |author= A. J. S. Rayl |title=Aging, in Theory: A Personal Pursuit |url=http://www.the-scientist.com/?articles.view/articleNo/14015/title/Aging--in-Theory--A-Personal-Pursuit/ |magazine= The Scientist|location= |publisher= |date= May 13, 2002 |access-date= }}</ref><ref>Leonid A. Gavrilov, Natalia S. Gavrilova; V.P. Skulachev (ed.); John and Liliya Payne (trans.) (1991). ''The Biology of Life Span: A Quantitative Approach''. Chur; New York: Harwood Academic Publishers. ISBN 9783718649839.</ref>||

|  1993 || Discovery ||Dr. [[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-16]]m.<ref>{{cite web|url=http://www.sfgate.com/magazine/article/Finding-the-Fountain-of-Youth-Where-will-UCSF-2667274.php|title= Finding the Fountain of Youth / Where will UCSF biochemist Cynthia Kenyon's age-bending experiments with worms lead us?}}</ref><ref>{{cite journal |vauthors=Kenyon C, Chang J, Gensch E, Rudner A, Tabtiang R | title=A C. elegans mutant that lives twice as long as wild type | journal=[[Nature (journal)|Nature]] | volume=366 | issue=6454 | year=1993 | pages=461–464 | pmid=8247153 | doi=10.1038/366461a0}}</ref> ||

|1994||Book||[[Leonard Hayflick]] publishes ''How and Why we Age''.<ref>{{cite web|url=https://repository.asu.edu/attachments/163946/content/Bartlett_asu_0010N_15494.pdf|title=A History of Cellular Senescence and Its Relation to Stem Cells in the Twentieth and Twenty-First Centuries  |author=Zane Bartlett |date=|accessdate=4 August 2016}}</ref>||

|1995||Development||Detection of [[senescent cell]]s using a [[cytochemical assay]] is first described.<ref>{{cite web|title=Senescence Associated β-galactosidase Staining|url=http://www.bio-protocol.org/e247|accessdate=20 August 2016}}</ref>||  

|2003|| Organization || Dr. [[Aubrey de Grey]] and [[David Gobel]] form the [[Methuselah Foundation]], which gives financial grants to anti-aging research projects.<ref>[http://mfoundation.org/about Methuselah Foundation - About]</ref> || [[Springfield, Virginia]], U.S.A.

|2009|| Organization || De Grey and several others found the [[SENS Research Foundation]] with aims at conducting research into aging and funding other anti-aging research projects at various universities.<ref>Ben Best (2013) [http://www.lef.org/magazine/mag2013/jul2013_Interview-with-Aubrey-de-Grey-PhD_01.htm "Interview with Aubrey de Grey, PhD"]. ''Life Extension Magazine''.</ref><ref>{{Cite news|title = Jason Hope|date = December 9, 2010 |publisher = Internet Entrepreneur Pledges A Donation To SENS Foundation - JasonHope.com|url = http://jasonhope.com/press/61-sens-foundation}}</ref><ref>[http://sens.org/files/pdf/2011_Research_Report.pdf research report 2011]. Sens Foundation</ref> ||[[Mountain View, California]], U.S.A

| 2010 || Achievement||[[Harvard university|Harvard]] scientists reverse aging process in mice through reactivation of [[telomerase]].<ref>{{cite web|url=https://www.theguardian.com/science/2010/nov/28/scientists-reverse-ageing-mice-humans |title=Harvard scientists reverse the ageing process in mice – now for humans }}</ref>||U.S.A.

|2013|| Organization || [[Google]] announces [[Calico (company)|Calico]], with the purpose of harnessing new technologies to increase scientific understanding of the biology of aging.<ref>{{cite web|url=http://www.cnn.com/2013/10/03/tech/innovation/google-calico-aging-death/|title=How Google's Calico aims to fight aging and 'solve death'|author=Arion McNicoll, Arion |date=3 October 2013|work=CNN}}</ref> ||[[San Francisco]], U.S.A

| 2016 || Discovery || Scientists demonstrate for the first time that [[mitochondria]] are major triggers of cell aging.<ref>{{cite journal |author=Clara Correia‐Melo, Francisco DM Marques, Rhys Anderson, Graeme Hewitt, Rachael Hewitt, John Cole, Bernadette M Carroll, Satomi Miwa, Jodie Birch, Alina Merz, Michael D Rushton, Michelle Charles, Diana Jurk, Stephen WG Tait, Rafal Czapiewski, Laura Greaves, Glyn Nelson, Mohammad Bohlooly‐Y, Sergio Rodriguez‐Cuenca, Antonio Vidal‐Puig, Derek Mann, Gabriele Saretzki, Giovanni Quarato, Douglas R Green, Peter D Adams, Thomas von Zglinicki, Viktor I Korolchuk, João F Passos |date= |title=Mitochondria are required for pro‐ageing features of the senescent phenotype |url=http://emboj.embopress.org/content/35/7/724 |journal=The EMBO Journal |publisher= |volume= 35|issue= |pages= 724–742|doi=10.15252/embj.201592862 |pmc= |pmid= 26848154 |year=2016}}</ref><ref>{{cite web|url=http://www.ncl.ac.uk/press/news/2016/02/mitochondriashowntotriggercellageing/|title=Mitochondria shown to trigger cell ageing}}</ref>|| [[Newcastle upon Tyne]], UK ([[Newcastle University]])

* [[Timeline of Alzheimer's disease]]

[[Category:Senescence]]

[[Category:Medicine timelines]]