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.

Full timeline[edit]

Year/period Type of Event Event Location
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.[1]
5th century 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.[2] 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 [3][4][5]
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.[6][7]
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.[8][9]
1913 Organization The Life Extension Institute is inaugurated as a longevity research center, with US president William Howard Taft as chairman.[10][11] 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.[12]
1934 Discovery Mary Crowell and Clive McCay of Cornell University discover that calorie restriction can extend lifespan twofold in rats.[13]
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.[11] 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.[12]
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.[1]
1957 Theory 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.[1][14]
1958 Theory 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.[11]
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.[15][16][17] Philadelphia
1965–1969 Discovery The strong effect of age on DNA methylation levels is discovered,[18] thus rendering it an accurate biological clock in humans and chimpanzees.[19]
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.[20] This theory becomes stronger through further experimental support during the following decades.[21][22]
1969 Book American physician Roy Walford publishes The Immunologic Theory of Aging, contributing to the basis for many current ideas about immunological aging.[23]
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.[24][25] Baltimore, U.S.A.
1975–1984 Discovery Elizabeth Blackburn discovers the unusual nature of telomeres, with their simple repeated DNA sequences composing chromosome ends.[26][27] 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.[28] Further experiments establish the role of telomere shortening in cellular aging and telomerase reactivation in cell immortalization.[29]
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.[30]
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.[31][32] 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.[33]
1991 Theory 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.[34][35]
1993 Discovery 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.[36][37]
1994 Book Leonard Hayflick publishes How and Why we Age.[38]
1995 Development Detection of senescent cells using a cytochemical assay is first described.[39]
2003 Organization Aubrey de Grey and David Gobel form the Methuselah Foundation, which gives financial grants to anti-aging research projects.[40] 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.[41][42][43] Mountain View, California, U.S.A
2010 Achievement Harvard scientists reverse aging process in mice through reactivation of telomerase.[44] U.S.A.
2013 Organization Google announces Calico, with the purpose of harnessing new technologies to increase scientific understanding of the biology of aging.[45] San Francisco, U.S.A
2017 Discovery Scientists knock out autophagy in the neurons of older worms resulting in a 50% boost to total longevity.[46]

See also[edit]


  1. ^ a b c Daniel Fabian; Thomas Flatt. "The Evolution of Aging". Nature.
  2. ^ Andrea Grignolio; Claudio Franceschi (2012). History of Research into Ageing/Senescence. eLS. doi:10.1002/9780470015902.a0023955. ISBN 978-0470016176.
  3. ^ "Gompertz, Benjamin" . Dictionary of National Biography. London: Smith, Elder & Co. 1885–1900.
  4. ^ Gompertz, B. (1825). "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". Philosophical Transactions of the Royal Society. 115: 513–585. doi:10.1098/rstl.1825.0026.
  5. ^ Leonid A. Gavrilov & Natalia S. Gavrilova (1991) The Biology of Life Span: A Quantitative Approach. New York: Harwood Academic Publisher, ISBN 3-7186-4983-7
  6. ^ "Biological Aging Theory - Frequently asked Questions and Answers".
  7. ^ "A Weismann".
  8. ^ Michael Ristow; Kathrin Schmeisser (2014). "Mitohormesis: Promoting Health and Lifespan by Increased Levels of Reactive Oxygen Species (ROS)". Dose-Response. 12 (2): 288–341. doi:10.2203/dose-response.13-035.Ristow. PMC 4036400. PMID 24910588.
  9. ^ Rubner, M. (1908). Das Problem det Lebensdaur und seiner beziehunger zum Wachstum und Ernarnhung. Munich: Oldenberg.
  10. ^ Hamowy, Ronald (2008-01-01). Government and Public Health in America. ISBN 9781847204257. Retrieved 21 December 2016.
  11. ^ a b c A History of Life-Extensionism In The Twentieth Century. Rison Lezion, Israel: Longevity History. 2014. ISBN 978-1500818579.
  12. ^ a b David Costantini (2014-03-27). Oxidative Stress and Hormesis in Evolutionary Ecology and Physiology. p. 306. ISBN 9783642546631.
  13. ^ Fossel, Michael. The Telomerase Revolution: The Enzyme That Holds the Key to Human Aging.
  14. ^ Williams, G.C. (1957). "Pleiotropy, natural selection and the evolution of senescence" (PDF). Evolution. 11 (4): 398–411. doi:10.2307/2406060. JSTOR 2406060. Archived from the original (PDF) on 2006-07-13. Cite uses deprecated parameter |deadurl= (help) Paper in which Williams describes his theory of antagonistic pleiotropy.
  15. ^ "Will the Hayflick limit keep us from living forever?". 2009-05-11.
  16. ^ Hayflick L, Moorhead PS (1961). "The serial cultivation of human diploid cell strains". Exp Cell Res. 25 (3): 585–621. doi:10.1016/0014-4827(61)90192-6. PMID 13905658.
  17. ^ Hayflick L. (1965). "The limited in vitro lifetime of human diploid cell strains". Exp. Cell Res. 37 (3): 614–636. doi:10.1016/0014-4827(65)90211-9. PMID 14315085.
  18. ^ Berdyshev, G; Korotaev, G; Boiarskikh, G; Vaniushin, B (1967). "Nucleotide composition of DNA and RNA from somatic tissues of humpback and its changes during spawning". Biokhimiia. 31: 88–993.
  19. ^ Horvath S (2013). "DNA methylation age of human tissues and cell types". Genome Biology. 14 (R115): R115. doi:10.1186/gb-2013-14-10-r115. PMC 4015143. PMID 24138928.
  20. ^ Alexander P (1967). "The role of DNA lesions in the processes leading to aging in mice". Symp. Soc. Exp. Biol. 21: 29–50. PMID 4860956.
  21. ^ Bernstein C, Bernstein H (1991). Aging, Sex, and DNA Repair. San Diego CA: Academic Press. ISBN 978-0123960030.
  22. ^ Ames BN, Gold LS (1991). "Endogenous mutagens and the causes of aging and cancer" (PDF). Mutat. Res. 250 (1–2): 3–16. doi:10.1016/0027-5107(91)90157-j. PMID 1944345.
  23. ^ Effros RB (2005). "Roy Walford and the immunologic theory of aging". Immun Ageing. 2 (1): 7. doi:10.1186/1742-4933-2-7. PMC 1131916. PMID 15850487.
  24. ^ Ofahengaue Vakalahi, Halaevalu F.; Simpson, Gaynell M.; Giunta, Nancy (2014-01-28). The Collective Spirit of Aging Across Cultures. p. 20. ISBN 9789401785945. Retrieved 21 December 2016.
  25. ^ "National Institute of Aging".
  27. ^ Blackburn AM; Gall, Joseph G. (March 1978). "A tandemly repeated sequence at the termini of the extrachromosomal ribosomal RNA genes in Tetrahymena". J. Mol. Biol. 120 (1): 33–53. doi:10.1016/0022-2836(78)90294-2. PMID 642006.
  28. ^ "The 2009 Nobel Prize in Physiology or Medicine - Press Release". Nobelprize.org. 2009-10-05. Retrieved 2012-06-12.
  29. ^ "Unravelling the secret of ageing". COSMOS: The Science of Everything. October 5, 2009. Archived from the original on July 3, 2014. Cite uses deprecated parameter |deadurl= (help)
  30. ^ Goldsmith, Theodore (2006). The Evolution of Aging: How New Theories Will Change the Future of Medicine. p. 48. ISBN 9780978870904.
  31. ^ Nuwer, Rachel (4 July 2014). "Keeping Track of the Oldest People in the World". Smithsonion.com. Retrieved 3 January 2015.
  32. ^ White, Gayle (8 February 2006). "Supercentenarians giving researchers clues on longevity". Chicago Tribune. Cox News Service. Retrieved 3 January 2015.
  33. ^ Greg Critser (2010-01-26). Eternity Soup: Inside the Quest to End Aging. ISBN 9780307462503.
  34. ^ A. J. S. Rayl (May 13, 2002). "Aging, in Theory: A Personal Pursuit". The Scientist.
  35. ^ 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.
  36. ^ "Finding the Fountain of Youth / Where will UCSF biochemist Cynthia Kenyon's age-bending experiments with worms lead us?". 2005-05-29.
  37. ^ Kenyon C, Chang J, Gensch E, Rudner A, Tabtiang R (1993). "A C. elegans mutant that lives twice as long as wild type". Nature. 366 (6454): 461–464. doi:10.1038/366461a0. PMID 8247153.
  38. ^ Zane Bartlett. "A History of Cellular Senescence and Its Relation to Stem Cells in the Twentieth and Twenty-First Centuries" (PDF). Retrieved 4 August 2016.
  39. ^ "Senescence Associated β-galactosidase Staining". Retrieved 20 August 2016.
  40. ^ Methuselah Foundation - About
  41. ^ Ben Best (2013) "Interview with Aubrey de Grey, PhD". Life Extension Magazine.
  42. ^ "Jason Hope". Internet Entrepreneur Pledges A Donation To SENS Foundation - JasonHope.com. December 9, 2010.
  43. ^ research report 2011. Sens Foundation
  44. ^ Sample, Ian; Correspondent, Science (2010-11-28). "Harvard scientists reverse the ageing process in mice – now for humans". The Guardian.
  45. ^ Arion McNicoll, Arion (3 October 2013). "How Google's Calico aims to fight aging and 'solve death'". CNN.
  46. ^ Neuronal inhibition of the autophagy nucleation complex extends life span in post-reproductive C. elegans.