Biology:Timeline of senescence research

From HandWiki
Short description: Timeline of notable events in the history of senescence research

This timeline lists notable events in the history of research into senescence or biological aging. People have long been interested in making their lives longer and healthier. The most anсient Egyptian, Indian and Chinese books contain reasoning about aging. Ancient Egyptians used garlic in large quantities to extend their lifespan. Hippocrates (c. 460 – c. 370 BC), in his Aphorisms, and Aristotle (384 – 322 BC), in On youth and old age, expressed their opinions about reasons for old age and gave advice about lifestyle. Medieval Persian physician Ibn Sina (c. 980 – 1037), known in the West as Avicenna, summarized the achievements of earlier generations about this issue.[1][2][3]


Descriptions of rejuvenation and immortality remedies are often found in the writings of alchemists. But all those remedies did not allow even alchemists themselves to live longer than a hundred years.[1][2][3]

Though the average lifespan of people through the past millennia increased significantly,[4] maximum lifespan almost did not change - even in ancient times there were fairly well and unbiasedly documented cases when some people lived for more than a hundred years (for example, Terentia who lived 103 or 104 years). While among the billions of people of the modern world, there is only one case of life over 120 years (Jeanne Calment, 122 years). The super-long lives of people that are mentioned in ancient books, apparently, are highly exaggerated, since archaeological data show that even the oldest of the ancient people lived no more than modern supercentenarians.[2] In some cases the exaggeration, possibly, is not intentional but occurs due to errors in translation between languages and synchronization of chronological systems. The species limit of human life is estimated by scientists at 125–127 years,[5][6] and even in the most ideal conditions a person will not live longer due to aging of the body.

Some scientists believe that, even if medicine learns how to treat all major diseases, that will increase the average lifespan of people in developed countries by only about 10 years.[2] For example, biogerontologist Leonard Hayflick stated that the natural average lifespan for humans is 92 years.[7] Meanwhile the life expectancy for Japanese already now is more than 84 years,[8] and for Monaco it is reported to be more than 89 years.[9] It may not be possible to achieve further increases without development of new biomedical technologies and approaches. Searches of various equivalents of the elixir of youth happened yet in ancient times: people hoped to find a miraculous remedy in faraway territories, tried to use magic and alchemy. Scientific and technological attempts began at the end of the 19th century. For their intended purpose, all of them turned out to be inefficient at best, sometimes led to premature death, but they had many useful and sometimes unexpected consequences.


Search for an elixir of youth in ancient times

  • 350 BC — The Greek philosopher Aristotle, arguably the first philosopher to make a serious attempt to scientifically explain aging, proposes his thesis on aging. He suggests that aging is a process by which human and animal bodies, which are naturally hot and wet, gradually become dry and cold, and theorizes that more moisture delays aging.[10][11]
  • 259–210 BC — years of life of the Chinese emperor Qin Shi Huang, who united China under his rule. All his life he persistently searched for an elixir of youth and died trying, presumably taking "pills of immortality", containing mercury.
  • 156–87 BC — years of life of the Chinese emperor Wu of Han, who persistently tried to find a way to achieve immortality, mainly by means of magic. He used services of various magicians. But Wu of Han was not a naive person – he thoroughly rechecked their abilities and if he identified the person as a quack, he executed him.
  • 63 BC–14 AD — years of life of Caesar Augustus, the first Roman emperor, who is considered one of the most effective leaders of the Ancient Rome. For him an eternal youth was an obsession. In particular, contrary to the Roman tradition to create statues as realistic as possible, he always ordered to portray himself young. There are many of his "youthful" statues but researchers still don't know how he looked in old age.
  • 3rd–17th century — the period of alchemy. There are several directions in alchemy, and it was distributed over a huge territory. But almost everywhere, in one form or another, there was the concept of a "philosopher's stone" – some substance that is able to turn other metals into gold, and when taken internally in small doses, heal all diseases, rejuvenate an old body and even give biological immortality. Alternatively, there were attempts to prepare "pills of immortality". During centuries alchemy gradually transformed to chemistry, in parallel giving birth to many adjacent sciences or enriching them. It is worth noticing the direction of iatrochemistry – a rational direction of alchemy with the main goal of preparing medicinal products. The pioneers of iatrochemistry were Paracelsus (1493–1541), Jan Baptist van Helmont (1580–1644) and Franciscus Sylvius (1614–1672). The converging field of alchemy was transformed into pharmacy.
  • 1513 — searching for the Fountain of Youth was one of the purposes of the expedition of the Spanish conquistador Juan Ponce de León, in the result of which Florida was discovered.
  • 1550 — a Venetian nobleman Luigi Cornaro published the book "The Art of Living Long", describing the style of life for the achievement of longevity.[12] The book was translated into many languages. The English version of the book till the 19th century went through more than 50 editions. The main idea of the book: in order to live many years, you need to live in moderation, eat simply and little. In his youth Cornaro led a free and immoderate life, as a result by the age of 35 he had many health problems. But by changing his lifestyle he was able to live to 98 (1467–1566).[13] (Though it is possible that he exaggerated his age by about 17 years to give his recommendations more weight.)

Scientific experiments from the end of the 19th century to WWII (the first steps)

From the end of the 19th century, systematic scientific and technical studies began on the processes of slowing down aging and possible rejuvenation. The period of world history between the two world wars is a very complicated, difficult and ambiguous time of world history. In many spheres of life, there were ideas that were radical-bold, but not always intelligent, ethical and moral from the point of view of modern knowledge, foundations and norms. This also affected the aging research, the spirit of which corresponded to the spirit of that time: attempting bold experiments, often on people, intensively implementing in practice treatments that we may now consider ridiculous. Those attempts had both bad and good consequences. But those researches were already scientific. As it often happens in science, it is often difficult to establish priority considering, who was the first person beginning to use one or another approach. Usually the first experiments are done by enthusiasts and have doubtful positive effects. Some researchers work in parallel. Then at some moment the persons emerge who developed the approaches and made them public.

  • 1825 The first publication of the Gompertz–Makeham law of mortality that in the simplest form is: p = a + bx. According to the law, the probability of death p is defined as the sum of age-independent component a and the component depending on age bx which with age increases exponentially. If we place organisms in an absolutely protected environment and in this way make the first component negligible, the probability of death will be completely defined by the second component which actually describes the probability to die from aging.
  • 1860s Alfred Russel Wallace writes down what is probably the first evolutionary theory of aging. In notes written sometime between 1865 and 1870, he proposed a wear and tear theory of aging, suggesting that older animals which continue to consume resources, competing with their offspring in an environment with limited food, were disfavored by natural selection. Therefore, he suggested that aging was an evolved trait which allowed an organism's descendants to thrive.[11]
  • 1882 August Weismann puts forward the wear and tear theory of aging independently of Wallace.[14][15]
  • 1889 Rejuvenation experiment conducted on himself by the French doctor Charles-Édouard Brown-Séquard. He made himself a few subcutaneous injections from the testicles of young dogs and guinea pigs and claimed that the injections were accompanied by significant and long pain, but then he observed an improvement of the physical condition of the organism and increase of mental activity. Experiments of other scientists, at first, produced the same results but later it became clear that the period of reinforced activity is followed by a period of decline. At the moment of the experiment Charles-Édouard Brown-Séquard was 72 years old. After the experiment he claimed he felt as if he became younger by 30 years. However, 5 years later he died. But other doctors picked up this method and it created the foundation for the development of hormone replacement therapy.[2][16][17][13]
  • 1903 Ilya Mechnikov coined the term "gerontology".[18][19][3] The term originates from the Greek γέρων, geron, "old man" and -λογία, -logia, "study of". From 1897 to 1916 Mechnikov conducted many studies on the effect of acidified dairy products (especially Bulgarian yogurt and bacteria used for its production) on longevity and quality of life in old age. He developed the concept of probiotic diet that promotes long healthy life.[16][17] In 1908 Mechnikov received the Nobel Prize for his work on immunology (adjacent area of his research).[20] Adhering to his diet, Mechnikov lived a very long life compared to his short-lived relatives.[21]
  • 1914 Dr. Frank Lydston from Chicago performed human testis transplants on several patients, including himself, and said that there were some rejuvenating consequences (such as returning his gray hair to its original color and improving of sexual performance).[13] These works remained little known. The work of Leo L. Stanley, that he began to do since 1919, received much more prominence (see further).
  • 1915–1917 Experiments to find out the effects of food restriction on the life duration of rats, conducted by Thomas Osborne. Apparently, these were the first systematic experiments in this direction.[2][22] These experiments remained little known. The method was popularized by Clive McCay in 1934–1935 (see further).
  • 1910s–1930s Austrian physiologist Eugen Steinach was trying to achieve rejuvenation effects by means of different surgical operations such as partial vasectomy for men, ligation of fallopian tubes for women, transplantation of testicles, etc. And although later these operations were found to be ineffective, they allowed the researchers to recognize the role of the sexual glands and sexual hormones in the formation of the first and secondary gender characteristics, enriched physiology, laid the foundation for the science of sexology, formed the basis for sex reassignment surgeries. From 1921 to 1938, Eugen Steinach was nominated for the Nobel Prize many times (according to various sources, from 6 to 11 times), but never received it.[16][17][23][24][25]
  • 1910s–1930s Numerous experiments for obtaining rejuvenating effects by means of transplantation of organs and tissues. Among the most notable researchers who worked in this direction, there were Alexis Carrel (who developed the technology of anastomosis of blood vessels and advanced asepsis, a Nobel laureate of 1912[26]), Mathieu Jaboulay, Emerich Ullmann, Jacques Loeb, John Northrop, Porfiry Bakhmetiev. And although such interventions were later found to be ineffective for their intended purposes, those works led to the creation of tissue engineering, techniques for cardiopulmonary bypass and dialysis, established the foundation for the technologies for storing organs extracted from a person outside the body (which now are used, for example, during organ donation), the emergence of cryobiology.[16][17]
  • 1920s–1930s In medical practice, sex gland transplants were introduced to obtain rejuvenating effects. (Though separate experiments in this direction were done even earlier, even in antiquity.) The earlier mentioned operations of Dr. Frank Lydston in 1914 remained almost unnoticed. But the works of Leo Leonidas Stanley quickly received widespread scientific notice. Stanley was a physician at a prison in California and began to do these operations since 1919, using glands of executed criminals.[13] In the following years, such operations were done by dozens of physicians (including Eugen Steinach) but they became most famous due to the activity of the French surgeon of Russian extraction Serge/Samuel Voronoff. It was believed that transplantation of sex glands provides more durable effects than injection of a suspension of ground glands. In case of transplantation from human to human, the glands of executed criminals were usually used. But due to a shortage of materials, the sex glands of young healthy monkeys were widely used, which were specially grown for this purpose (usually thin sections of the glands were implanted). In some cases soon after the operation, there were indeed noticeable positive changes in appearance and behavior (with a rapid senility of the body soon following). There were many messages about wonderful results of the operations that, apparently, were false advertising of unscrupulous doctors. But numerous failures became apparent, for which the method was sharply criticized and banned.[2] Serge Voronoff and some other doctors, who claimed producing wonderful results after the operations, got bad reputation. However, despite the failure in the main direction, the conducted research led to the emergence of allotransplantation and xenotransplantation directions in surgery, brought significant knowledge about the effect of sex hormones on the body, stimulated their study.[16][17] It may be just a coincidence but in 1929–33 several varieties of estrogen were discovered, and testosterone was isolated in 1935. Also these experiments formed the basis for several works of public culture (for example, Heart of a Dog by Mikhail Bulgakov, The Adventure of the Creeping Man from the series about Sherlock Holmes, a song Monkey-Doodle-Doo of Irving Berlin).
  • 1926–1928 Experiments on rejuvenation by blood transfusion, conducted by Alexander Bogdanov in the world's first Institute for Blood Transfusion especially created for that purpose. Bogdanov himself died during one of the experiments, because at that time little was known about the factors of blood compatibility of different people.[2][17] The institute, having undergone several renames, exists and is still actively working. The second head of the institute was Alexander Bogomolets (see further).
  • 1930s Beginning of attempts of rejuvenation by methods of cell injections. A special role belongs here to the Swiss physician Paul Niehans – he was not the first but he was the one who developed this approach the most. Among his patients there were many famous people (including Winston Churchill, Charles de Gaulle, Pope Pius XII).[2][16] So, in 1952, about 3000 injections of about 10 cm3 of cell suspension were reported. As a consequence, cell therapy and regenerative medicine were formed. Since the 1960s, attempts have been made to inject not only whole cells but also their constituent parts (such as isolated DNA and RNA).[16][17] But usage of embryonic drugs sometimes caused serious complications, so the American association of physicians recognized the method of cell therapy as dangerous.[2]
  • 1930 The first world's journal about aging and longevity. It was established in Japan and has the name Acta Gerontologica Japonica (Yokufuen Chosa Kenkyu Kiyo).[27]
  • 1933 The first institute in the world dedicated to study of aging. It was created in Kishinev (at that time inside the Kingdom of Romania) by Dimu Kotsovsky. Initially the institute was maintained by his own means, and was subsequently recognized by the Romanian government. The name is Romanian: Institutul Pentru Studierea si Combaterea Batranetii = German: Institut für Altersforschung und Altersbekämpfung = Institute for The Study and Combat of Aging.[28]
  • 1934 The first widely known scientific publication on the impact of dietary restriction on life expectancy, authored by Clive McCay.[29][30][31] McCay's group carried out intensive research in this direction in 1930-43, soon other scientists began to do related research.[2] The effect of increasing life expectancy by starvation is usually observed in rats and mice, whose development until puberty is very labile (growth retardation and puberty, decreased metabolism and body temperature). In larger animals, such as rabbits, dogs and monkeys, the effect is less pronounced. The impact of fasting on human life expectancy still remains a question where not everything is clear and is unambiguous.[2]
  • 1936 The first European (and Western) journal about aging and longevity. It was published in Kishinev by Dimu Kotsovsky. During the first year of existence it was called Monatsberichte,[32] then got the name German: Altersprobleme: Zeitschrift für Internationale Altersforschung und Altersbekämpfung = "Problems of Aging: Journal for the International Study and Combat of Aging". The journal published materials mostly in the German language, less in French and English.[28]
  • 1937 A Ukrainian Soviet pathophysiologist Alexander Bogomolets created antireticular cytotoxic serum in the hope to extend life of people to 150 years. Although the drug did not achieve its main goal, it has become widely used for the treatment of a number of diseases, especially infectious diseases and fractures.[2][16][17] The serum of Bogomolets was actively used in Soviet hospitals during WWII. For his work, Alexander Bogomolets received in 1941 the Stalin Prize,[33] which for Soviet scientists of those years was even more important than the Nobel Prize.
  • 1938 The first specialized society dedicated to the study of aging. It was formed in Germany, Leipzig and was named the German Society for Aging Research (German: Deutsche Gesellschaft für Altersforschung, soon renamed to Deutsche Gesellschaft für Alternsforschung). The founder is Max Bürger (de). He also established the specialized journal Zeitschrift für Altersforschung – it is already the third such journal in the world after the previously mentioned Japanese and Romanian journals.[34]
  • 1938 The world's first scientific conference on aging and longevity in 1938 in Kiev, that was convened by Alexander Bogomolets.[1][35]
  • 1939 In the United Kingdom, the British Society for Research on Ageing is formed. The founder is Vladimir Korenchevsky who emigrated there from the former Russian Empire.[1]

After WWII until the end of the 20th century (accumulation of modern knowledge)

After World War II, research tools and technologies of another level appeared. Thanks to these technologies, it became understandable what really occurs inside cells and between them (for example, the model of the DNA double helix was created in 1953). At the same time, changed ethical norms did not allow cardinal experiments to be performed on humans, as had been possible in previous decades. Consequently, the influence of different factors could be estimated only indirectly.

  • 1945 In the USA, the Gerontological Society of America is formed. The founder is Edmund Vincent Cowdry.[1]
  • 1950 Largely thanks to the collaborative efforts of Korenchevsky and Cowdry, the International Association of Gerontology is formed, later renamed to the International Association of Gerontology and Geriatrics (IAGG). The organization was registered in Belgium, and that is where its first conference took place. Slowly, gradually, the ideas began to spread that the problems of aging cannot be solved within the framework and efforts of one nation – therefore the international interaction is necessary.[1]
  • 1952 Peter Medawar proposed the mutation accumulation theory to explain how the aging process could have evolved.[14][36][4]
  • 1954 Vladimir Dilman formulated the hypothesis of aging that at first become known only in the USSR, as the elevation hypothesis. In 1968 it took the form and became known as the neuroendocrine theory of aging.[37][38][39]
  • 1956 Denham Harman proposed the free-radical theory of aging and demonstrated that free radical reactions contribute to the degradation of biological systems.[40] The theory is based on the ideas of Rebeca Gerschman and her colleagues put forward in 1945.[41]
  • 1957 George Williams proposed the antagonistic pleiotropy hypothesis for the explanation of the emergence of aging.[4][42]
  • 1958 Physicist Gioacchino Failla proposed the hypothesis that aging is caused by the accumulation of DNA damage.[43] The next year the hypothesis was developed by the physicist Leo Szilard,[44] resulting in a number of related theories under the general name DNA damage theory of aging.
  • 1961 Discovery by Leonard Hayflick of the limit of divisions for somatic cells, named the Hayflick limit. Hayflick found that normal human cells, extracted from fetus, are able to divide only about 50 times, after that they enter a senescence phase.
  • 1969 Immunological theory of aging proposed by Roy Walford.[45]
  • 1974 Formation of the National Institute on Aging (NIA) – the aging of the population began to be perceived as a problem deserving state attention (and not as a problem of separate scientific societies). Since 1984, the NIA has begun to contribute in every way to the work of the National Archive of Computerized Data on Aging (NACDA).
  • 1977 To explain aging, Thomas Kirkwood proposed the disposable soma theory. According to the theory, the organism has only a limited amount of resources that it has to allocate between different purposes (such as growth, reproduction, repair of damage). Aging occurs due to the limitation of resources that the body can afford to spend on repair.[4]
  • 1985 The discovery of telomerase, a ribonucleoprotein that is able to restore shortened telomeres. The discovery was made by Elizabeth Blackburn and Carol Greider.[46][47] This research is based on the theoretical works of Alexey Olovnikov.[47][48][49] The study of telomeres and telomerase required many more years and the work of many scientists around the world. For this work, in 2009, Elizabeth Blackburn, Carol Greider and Jack Szostak received the Nobel prize,[50] in the same year Alexey Olovnikov was awarded the Demidov Prize.[51]
  • 1986 Reliability theory of aging and longevity proposed by Leonid Gavrilov and Natalia Gavrilova. At first it was published only in the USSR.[52] In English language the theory was published five years later, in 1991.[53][54][55]
  • 1990 Formation of the Gerontology Research Group (GRG) which searches for supercentenarians around the world and verifies their age. Whenever possible, the organization tries to collect data on why these people live significantly longer than the average person. The organization regularly publishes a list of the oldest verified living supercentenarians.[56]
  • 1992 National Archive of Computerized Data on Aging (NACDA) published in the Internet the first 28 datasets related to aging. Gradually the number of published datasets has grown to over 1600 and continues to grow. These datasets are available to any researcher around the world at no charge, so they can search in them for new patterns. The site also provides some tools to facilitate analysis.[57]
  • 1993 Cynthia Kenyon and Ramon Tabtiang doubled the lifespan of C. elegans nematodes by partially disabling a gene, with the nematodes remaining relatively healthy for significantly longer. The discovery was a revolutionary breakthrough in aging research, demonstrating that the aging process could be controlled in the laboratory, and sparked more research into the molecular biology of aging.[58][59]
  • 1995 Method for detection of senescent cells using a cytochemical assay.[60]
  • 1997 The absolute record for the duration of human life. The French woman Jeanne Calment lived 122 years and 164 days (the record is still held).
  • 1998 A record for the duration of life among males. The American of Danish descent Christian Mortensen lived 115 years and 252 days.
  • 1998 Scientists managed to extend, in a laboratory environment, the life of normal human cells beyond the Hayflick limit using telomerase.[47][61]
  • 1999 Establishment of the Buck Institute for Research on Aging – the first institute originally established primarily to study intervention into the aging process.

21st century (transforming knowledge into technology)

The research activity has increased. There is a shift of focus of the scientific community from the passive study of aging and theorizing to research aimed at intervening in the aging process in order to extend the lives of organisms beyond their genetic limits. Scientific-commercial companies appear, which aim to create practical technologies for measuring the biological age of a person (in contrast to chronological age) and extend the life of people to a greater extend than the healthy lifestyle and preventive medicine can provide. In society and media there are discussions not only about whether a significant prolongation of life is physically possible, but also whether it is appropriate, about the possibility of officially classifying aging as a disease, and about the possibility of mass testing on human volunteers.

  • 2003 First evidence that aging of nematodes is regulated via TOR signaling.[29][62]
  • 2003 The Methuselah Foundation is organized to create life extension technologies based on Strategies for engineered negligible senescence (SENS) approaches and supporting related research in other organizations. In 2009 the scientific research activity was transferred to the SENS Research Foundation that spun out from the Methuselah Foundation.
  • 2003 Andrzej Bartke created a mouse that lived 1819 days (5 years without 7 days), while the maximum lifespan for this species is 1030–1070 days.[2] By human standards, such longevity is equivalent to about 180 years.[63]
  • 2004 First evidence that aging of nematodes is regulated by AMP-Kinase.[29][64]
  • 2004 Aubrey de Grey coined the term "longevity escape velocity" (LEV).[65] Though the concept per se has been present in the life extension community since at least the 1970s (for example, Robert Wilson, essay Next Stop, Immortality, 1978[66]).
  • 2004 As a result of the use of anti-aging therapy, a team of scientists led by Stephen Spindler managed to extend the life of a group of already adult mice to an average of 3.5 years. For this achievement, the first Methuselah Mouse Rejuvenation 'M Prize' was awarded.[67]
  • 2004 Creation of the first curated database of genes related to human ageing: GenAge.[68]
  • 2006 Creation of induced stem cells (iSC) from somatic cells by the simultaneous action of several factors. First produced by the Japanese scientist Shinya Yamanaka.[69][70][71] In 2012, Shinya Yamanaka and John Gurdon received the Nobel Prize for their work on reprogramming mature cells into pluripotent cells.[72]
  • 2007 Extension of mouse lifespan via deletion of insulin receptor in the brain.[29][73]
  • 2007 The book Ending Aging written by Aubrey de Grey and his research assistant Michael Rae.
  • 2007 First evidence that a pharmacological agent (namely, metformin) at a certain dosage is capable to increase the lifespan of mice.[29][74]
  • 2008 Foundation of the Max Planck Institute for Biology of Ageing.
  • 2008 (approximately) It was observed that different variants of FOXO3 gene are associated with human longevity. Since then, research has been conducted to better understand its functions and the mechanism of action.[75][76][77][78]
  • 2009 Association of genetic variants in insulin/IGF1 signaling with human longevity.[29][79]
  • 2009 A second pharmacological agent (namely, rapamycin) was shown to be capable to increase the lifespan of mice. For this discovery Davе Sharp receive a special prize from the Methuselah Foundation.[29][80][81]
  • 2010s first half The appearance of small political parties in different countries that make the promotion of anti-aging technologies part of their political platforms (for example, Science Party of Australia, U.S. Transhumanist Party, Partei für Gesundheitsforschung).
  • 2012 It was discovered that protein Sirtuin 6 (SIRT6) regulates the lifespan of male mice (but not female mice).[29][82]
  • 2013 The scientific journal Cell published the article "The Hallmarks of Aging", that was translated to several languages and determined the directions of many studies.[83]
  • 2013 A record for the duration of life among males. Japanese Jiroemon Kimura lived 115 years and 54 days (that is 167 days longer than the previous record).
  • 2013 It was discovered that brain-specific overexpression of Sirtuin 1 (SIRT1) is also capable to extend lifespan and delay aging in mice.[29][84]
  • 2013 Google and other investors created the company Calico to combat aging and related diseases. Investors provided Calico with more than a billion dollars of funding. Arthur Levinson became CEO of the company and one of its investors.[85][86][87][88]
  • 2014 First evidence that pharmacological activation of SIRT1 extends lifespan in mice and improves their health.[29][89][90]
  • 2010s second half The emergence of official discussions about the possibility of recognizing aging as a disease.[91][92][93][94][95]
  • 2016 It was found that the replenishment of NAD+ in the organism of mice through precursor molecules improves the functioning of mitochondria and stem cells, and also leads to an increase in their lifespan.[29][96] One of these NAD+ precursor molecules is NMN.[97][98]
  • 2016 Demonstration that a combination of longevity associated drugs can additively extend lifespan, at least in mice.[29][99]
  • 2016 As part of the implementation of the SENS programs, researchers managed to make two mitochondrial genes, ATP8 and ATP6, stably express from the cell nucleus in the cell culture.[100]
  • 2016 Scientists show that expressing Yamanaka reprogramming factors in mice with premature aging can extend their lifespan by about 20%.[101][102][103]
  • 2017 The discovery that a naturally occurring polymorphism in human signaling pathways is in some cases associated with health and longevity. It was also detected that, the same as in mice, this association can depend on the gender (it can be observed for one gender but not for another). This indicates that by correctly influencing these pathways, it is theoretically possible to alter lifespan and healthspan in humans.[29][104]
  • 2018 The Nobel Prize for cancer research was awarded to James Allison and Tasuku Honjo.[105] (The main cause of cancer is the accumulation of errors in DNA. So the topic of cancer research is closely related to research on aging.)
  • 2018 The World Health Organization included in the international classification of diseases ICD-11 a special additional code XT9T, signaling the relationship of a disease with age. Due to this, after the final approval of the ICD-11 in May 2019, aging began to be officially recognized as a fundamental factor that increases the risk of diseases, the severity of their course and the difficulty of treatment.[106][107][108][109][110]


  • The lifespan of Caenorhabditis elegans (free-living nematodes) was increased by 5–6 times (by 400–500%) using simultaneous impact in IIS and TOR pathways. This is equivalent to how a human would live 400–500 years.[111][112][113][114]
  • Scientists at the Mayo Clinic report the first successful use of senolytics, a new class of drug with potential anti-aging benefits, to remove senescent cells from human patients with a kidney disease.[115][116]
  • By combining doses of lithium, trametinib and rapamycin into a single treatment, researchers extend the lifespan of fruit flies (Drosophila) by 48%.[117][118]
  • Researchers at Harvard Medical School identify a link between neural activity and human longevity. Neural excitation is linked to shorter life, while suppression of overactivity appears to extend lifespan.[119][120]
  • Scientists in Japan use single-cell RNA analysis to find that supercentenarians have an excess of cytotoxic CD4 T-cells, a type of immune cell.[121][122]


  • Scientists report, using public biological data on 1.75 m people with known lifespans overall, to have identified 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 – as well as haem metabolism as a promising candidate for further research within the field.[123][124]
  • Scientists report that after mice exercise their livers secrete the protein GPLD1, which is also elevated in elderly humans who exercise regularly, that this is associated with improved cognitive function in aged mice and that increasing the amount of GPLD1 produced by the mouse liver in old mice could yield many benefits of regular exercise for their brains – such as increased BDNF-levels, neurogenesis, and improved cognitive functioning in tests.[125][126]
  • Scientists report that yeast cells of the same genetic material and within the same environment age in two distinct ways, describe a biomolecular mechanism that can determine which process dominates during aging and genetically engineer a novel aging route with substantially extended lifespan.[127][128]
  • Reprogramming progress[129]
    • Scientists show that expression of nuclear reprogramming factors can lead to rapid and broad amelioration of cellular aging.[130][131][132]
    • A study shows that reprogramming induced with the OSK-genes can restore youthful epigenetic patterns as well as revert age-related vision loss.[133][134]



  • The American biotechnology company Altos Labs is founded.[161]
Expected life years gained for 20-year-olds in U.S. who change from a typical Western diet to an, according to an integrative study, "optimized diet" (changes indicated on the left in gram)[162]
  • A study integrates meta-analyses and data in a tool that shows populations' relative general life extension potentials of different food groups according to this available data, mostly consisting of observational studies.[163][162]
  • Results from the first controlled trial of caloric restriction in healthy non-obese humans, CALERIE, are published, confirming benefits and identifying a key protein that could be harnessed to extend health in humans, PLA2G7.[164][165]
  • A new cellular rejuvenation therapy of bursts of iPSC reprogramming is reported, which can reverse aspects of aging in mice, without causing cancer or other health problems.[166][167]
  • Researchers report that the widely used supplements glycine and NAC when combined as "GlyNAC", which previously showed various beneficial effects in humans i.a. in a small trial by the authors,[168] can extend lifespan by 24% in mice when taken at old age.[169][170]
  • Biomedical gerontologists demonstrate a mechanism of anti-aging senolytics, in particular of Dasatinib plus Quercetin (D+Q) – an increase of α-Klotho as shown in mice, human cells and in a human trial.[171][172]
  • Scientists reversed aging in human skin cells for over 30 years by partially reprogramming them with the Yamanaka factors, working better than previous reprogramming methods.[173][174]
  • Bioresearchers demonstrate an in vitro method (MPTR) for rejuvenation (including the transcriptome and epigenome) reprogramming in which fibroblast skin cells temporarily lose their cell identity.[175][176]
  • A comprehensive review reaffirms likely beneficial health effects with links to health/life extension of cycles of caloric restriction and intermittent fasting as well as reducing meat consumption in humans. It identifies issues with contemporary nutrition research approaches, proposing a multi-pillar approach, and summarizes findings towards constructing – multi-system-considering and at least age-personalized dynamic – refined longevity diets and proposes inclusion of such in standard preventive healthcare.[177][178]
  • A study demonstrates that a 30% caloric restriction extended life spans of male C57BL/6J mice by 10% but when combined with daily intermittent fasting and eating during the most active time of the day it extended life span by 35%.[179][180]
  • A study shows that infusing the nourishing cerebrospinal fluid from around brain cells of young mice into aged brains rejuvenates aspects of the brain, identifying FGF17 as a key target for potential therapeutics such as of anti-aging.[181][182][183]
  • A study shows the clonal diversity of stem cells that produce blood cells gets drastically reduced around age 70 to a faster-growing few, substantiating a novel theory of ageing which could enable healthy aging.[184][185]
See also: Stem cell theory of aging#Hematopoietic stem cell diversity aging
  • A study shows that blood cells' loss of the Y chromosome in a subset of cells with age, reportedly affecting at least 40% of 70 years-old men to some degree, contributes to fibrosis, heart risks, and mortality in a causal way.[186][187]
See also: Stem cell theory of aging#Hematopoietic mosaic loss of chromosome Y
  • A study reports that in model animals, treatment with rapamycin – which typically has negative side-effects – for a limited timespan extended lifespan as much as life-long administration started at the same age and that it was most effective during early adulthood.[188][189]
T. dohrnii

See also

Template:Science year nav

Fields not included

Research domains related or part of senescence research currently not fully included in the timeline:

  • Senolytic
  • Establishments of new research-conducting organizations, especially companies (see template at the bottom)
  • Research into centenarians
  • Ageing research projects and prizes

Excluded fields of research

Notable events in these fields of research that relate to life extension and healthspan are currently deliberately not included in this timeline


  1. 1.0 1.1 1.2 1.3 1.4 1.5 Ilia Stambler (January 2019). "History of Life-Extensionism". Encyclopedia of Biomedical Gerontology: 228–237. doi:10.1016/B978-0-12-801238-3.11331-5. ISBN 9780128012383. Retrieved 5 May 2021. 
  2. 2.00 2.01 2.02 2.03 2.04 2.05 2.06 2.07 2.08 2.09 2.10 2.11 2.12 2.13 В.Е. Чернилевский, В.Н. Крутько (2000). "История изучения средств продления жизни" (in ru). National Gerontology Center (of Russia). 
  3. 3.0 3.1 3.2 "History of Research into Ageing/Senescence". eLS. American Cancer Society. 15 June 2012. doi:10.1002/9780470015902.a0023955. ISBN 978-0470016176. 
  4. 4.0 4.1 4.2 4.3 "Ageing Throughout History: The Evolution of Human Lifespan". Journal of Molecular Evolution 88 (1): 57–65. January 2020. doi:10.1007/s00239-019-09896-2. PMID 31197416. Bibcode2020JMolE..88...57K. 
  5. "Health span approximates life span among many supercentenarians: compression of morbidity at the approximate limit of life span". The Journals of Gerontology: Series A 67 (4): 395–405. April 2012. doi:10.1093/gerona/glr223. PMID 22219514. 
  6. "Theoretical estimation of maximum human lifespan". Biogerontology 10 (1): 65–71. February 2009. doi:10.1007/s10522-008-9156-4. PMID 18560989. 
  7. "Leonard Hayflick and the limits of ageing". The Lancet 377 (9783): 2075. June 2011. doi:10.1016/S0140-6736(11)60908-2. PMID 21684371. 
  8. "Life expectancy and Healthy life expectancy, data by country" (in en). World Health Organization. 4 December 2020. 
  9. "Life expectancy at birth". CIA World Factbook. 5 May 2021. 
  10. Woodcox, Adam: Aristotle’s Theory of Aging
  11. 11.0 11.1 Steele, Andrew: Ageless: The New Science of Getting Older Without Getting Old
  12. (in en) The Art of Living Long. Forgotten Books. 2016. pp. 214. ISBN 978-1-330-67886-2. 
  13. 13.0 13.1 13.2 13.3 "Life extension and history: the continual search for the fountain of youth". The Journals of Gerontology: Series A 59 (6): B515-22. June 2004. doi:10.1093/gerona/59.6.B515. PMID 15215256. 
  14. 14.0 14.1 "Biological theories of aging". Disease-a-Month 61 (11): 460–6. November 2015. doi:10.1016/j.disamonth.2015.09.005. PMID 26490576. 
  15. Jessica Kelly. "Wear-and-Tear Theory". Lumen Learning. 
  16. 16.0 16.1 16.2 16.3 16.4 16.5 16.6 16.7 "The unexpected outcomes of anti-aging, rejuvenation, and life extension studies: an origin of modern therapies". Rejuvenation Research 17 (3): 297–305. June 2014. doi:10.1089/rej.2013.1527. PMID 24524368. 
  17. 17.0 17.1 17.2 17.3 17.4 17.5 17.6 17.7 Ilia Stambler (17 February 2021). "Have anti-aging interventions worked? Some lessons from the history of anti-aging experiments" (video). YouTube. 
  18. Dictionary of Gerontology. New York: Greenwood Press. 1988. p. 80. ISBN 9780313252877. 
  19. (in en) The Nature of Man: Studies in Optimistic Philosophy. New York and London: G.P. Putnam's Sons. 1903. OCLC 173625. 
  20. "The Nobel Prize in Physiology or Medicine 1908". 
  21. International Longevity Alliance (13 February 2021). "ILA Conference – Metchnikoff Day" (video). YouTube. 
  22. "The Effect of Retardation of Growth Upon the Breeding Period and Duration of Life of Rats". Science 45 (1160): 294–5. March 1917. doi:10.1126/science.45.1160.294. PMID 17760202. Bibcode1917Sci....45..294O. 
  23. "Eugen Steinach: the first neuroendocrinologist". Endocrinology 155 (3): 688–95. March 2014. doi:10.1210/en.2013-1816. PMID 24302628. 
  24. "Ageing: Rejuvenation study stirs old memories". Nature 546 (7656): 33. May 2017. doi:10.1038/546033e. PMID 28569802. Bibcode2017Natur.546...33K. 
  25. "Nomination Archive | Eugen Steinach". April 2020. 
  26. "The Nobel Prize in Physiology or Medicine 1912". 
  27. Stambler, Ilia (29 August 2014). "reference No. 438". A History of Life-Extensionism in the Twentieth Century. Longevity History. pp. 540. ISBN 978-1500818579. 
  28. 28.0 28.1 Stambler, Ilia (29 August 2014). "Allies – The Kingdom of Great Romania. Dimu Kotsovsky". A History of Life-Extensionism in the Twentieth Century. Longevity History. pp. 540. ISBN 978-1500818579. 
  29. 29.00 29.01 29.02 29.03 29.04 29.05 29.06 29.07 29.08 29.09 29.10 29.11 29.12 "A brief history of modern aging research". Experimental Gerontology 104: 35–42. April 2018. doi:10.1016/j.exger.2018.01.018. PMID 29355705. 
  30. "Prolonging the Life Span". The Scientific Monthly 39 (5): 405–414. October 1934. Bibcode1934SciMo..39..405M. 
  31. "The Effect of Retarded Growth Upon the Length of Life Span and Upon the Ultimate Body Size". The Journal of Nutrition 10 (1): 63–79. 1 July 1935. doi:10.1093/jn/10.1.63. 
  32. A cover scan of the first issue of the journal Monatsberichte
  33. "Alexander Alexandrovich Bogomolets: biography, scientific works, the basics of the theory". 
  34. Stambler, Ilia (29 August 2014). "Institutionalization of gerontology – Max Bürger". A History of Life-Extensionism in the Twentieth Century. Longevity History. pp. 540. ISBN 978-1500818579. 
  35. (in ru) Старость. (Труды конференции по проблеме генеза старости и профилактики преждевременного стрения организма). Kiev: UkrSSR Academy of Sciences Publishing House. 1939. pp. 490. 
  36. Medawar P.B. (1952). Lewis. ed. An Unresolved Problem in Biology. London. 
  37. Ward Dean (22 March 2012). Neuroendocrine Theory of Aging. Retrieved 5 May 2021. 
  38. "Age-associated elevation of hypothalamic, threshold to feedback control, and its role in development, ageine, and disease". The Lancet 1 (7711): 1211–9. June 1971. doi:10.1016/s0140-6736(71)91721-1. PMID 4103080. 
  39. "Neuroendocrine-ontogenetic mechanism of aging: toward an integrated theory of aging". International Review of Neurobiology 28: 89–156. 1986. doi:10.1016/S0074-7742(08)60107-5. ISBN 9780123668288. PMID 3542876. 
  40. "The aging process". Proceedings of the National Academy of Sciences of the United States of America 78 (11): 7124–8. November 1981. doi:10.1073/pnas.78.11.7124. PMID 6947277. Bibcode1981PNAS...78.7124H. 
  41. "Oxygen poisoning and x-irradiation: a mechanism in common". Science 119 (3097): 623–6. May 1954. doi:10.1126/science.119.3097.623. PMID 13156638. Bibcode1954Sci...119..623G. 
  42. Williams G.C. (1957). "Pleiotropy, natural selection, and the evolution of senescence". Evolution 11 (4): 398–411. doi:10.2307/2406060. 
  43. "The aging process and cancerogenesis". Annals of the New York Academy of Sciences 71 (6): 1124–40. September 1958. doi:10.1111/j.1749-6632.1958.tb46828.x. PMID 13583876. Bibcode1958NYASA..71.1124F. 
  44. "On the Nature of the Aging Process". Proceedings of the National Academy of Sciences of the United States of America 45 (1): 30–45. January 1959. doi:10.1073/pnas.45.1.30. PMID 16590351. Bibcode1959PNAS...45...30S. 
  45. "Selected Theories of Aging". Higher School's Pulse 10: 36–39. 2016. 
  46. "Identification of a specific telomere terminal transferase activity in Tetrahymena extracts". Cell 43 (2 Pt 1): 405–13. December 1985. doi:10.1016/0092-8674(85)90170-9. PMID 3907856. 
  47. 47.0 47.1 47.2 "Diurnal variation of intraocular pressure of normal-tension glaucoma. Influence of sleep and arousal". Ophthalmology 98 (3): 296–300. March 1991. doi:10.1038/onc.2010.15. PMID 2023748. 
  48. "[Principle of marginotomy in template synthesis of polynucleotides]" (in ru). Doklady Akademii Nauk SSSR 201 (6): 1496–9. 1971. PMID 5158754. 
  49. "A theory of marginotomy. The incomplete copying of template margin in enzymic synthesis of polynucleotides and biological significance of the phenomenon". Journal of Theoretical Biology 41 (1): 181–90. September 1973. doi:10.1016/0022-5193(73)90198-7. PMID 4754905. Bibcode1973JThBi..41..181O. 
  50. "The 2009 Nobel Prize in Physiology or Medicine – Illustrated Presentation". 
  51. Yegorov, Yegor; Zelenin, A.V. (13 February 2011). "Racing for cell immortality, telomeres, telomerase, and the measure of health". Russian Journal of Developmental Biology 42 (1): 53–56. doi:10.1134/S1062360411010061. PMID 21442903. 
  52. (in ru) Биология продолжительности жизни: Количественные аспекты (1st ed.). Moscow: Nauka. 1986. pp. 167. 
  53. (in en) Biology of Life Span: A Quantitative Approach (1st ed.). New York: Chur. 1991. pp. 385. ISBN 978-3718649839. 
  54. "The reliability theory of aging and longevity". Journal of Theoretical Biology 213 (4): 527–45. December 2001. doi:10.1006/jtbi.2001.2430. PMID 11742523. Bibcode2001JThBi.213..527G. 
  55. A.J.S. Rayl (13 May 2002). "Aging, in Theory: A Personal Pursuit. Do body system redundancies hold the key?". The Scientist 16 (10): 20. 
  56. "GRG World Supercentenarian Rankings List". Gerontology Research Group. 
  57. "About Us". NACDA. 
  58. Cynthia Kenyon: 'The idea that ageing was subject to control was completely unexpected'
  59. Cynthia Kenyon, PhD
  60. "Senescence Associated β-galactosidase Staining". Bio-Protocol 2 (16). 20 August 2012. doi:10.21769/BioProtoc.247. 
  61. "Extension of life-span by introduction of telomerase into normal human cells". Science 279 (5349): 349–52. January 1998. doi:10.1126/science.279.5349.349. PMID 9454332. Bibcode1998Sci...279..349B. 
  62. "Genetics: influence of TOR kinase on lifespan in C. elegans". Nature 426 (6967): 620. December 2003. doi:10.1038/426620a. PMID 14668850. Bibcode2003Natur.426..620V. 
  63. Valerie Sprague (4 September 2003). "Battle for 'old mouse' prize". BBC News Online. 
  64. "The AMP-activated protein kinase AAK-2 links energy levels and insulin-like signals to lifespan in C. elegans". Genes & Development 18 (24): 3004–9. December 2004. doi:10.1101/gad.1255404. PMID 15574588. 
  65. "The unfortunate influence of the weather on the rate of ageing: why human caloric restriction or its emulation may only extend life expectancy by 2–3 years". Gerontology 51 (2): 73–82. 15 June 2004. doi:10.1159/000082192. PMID 15711074. 
  66. Robert Anton Wilson (November 1978). "Next Stop, Immortality". Future Life (6). 
  67. Bill Christensen (1 December 2004). "First Methuselah Mouse Rejuvenation 'M Prize' Awarded". Live Science. 
  68. Magalhães, João Pedro de; Toussaint, Olivier (2004). "GenAge: a genomic and proteomic network map of human ageing" (in en). FEBS Letters 571 (1–3): 243–247. doi:10.1016/j.febslet.2004.07.006. ISSN 1873-3468. PMID 15280050. 
  69. "Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors". Cell 126 (4): 663–76. August 2006. doi:10.1016/j.cell.2006.07.024. PMID 16904174. 
  70. "Induction of pluripotent stem cells from adult human fibroblasts by defined factors". Cell 131 (5): 861–72. November 2007. doi:10.1016/j.cell.2007.11.019. PMID 18035408. 
  71. "Generation of germline-competent induced pluripotent stem cells". Nature 448 (7151): 313–7. July 2007. doi:10.1038/nature05934. PMID 17554338. Bibcode2007Natur.448..313O. 
  72. "The Nobel Prize in Physiology or Medicine 2012". 
  73. "Brain IRS2 signaling coordinates life span and nutrient homeostasis". Science 317 (5836): 369–72. July 2007. doi:10.1126/science.1142179. PMID 17641201. Bibcode2007Sci...317..369T. 
  74. "Metformin slows down aging and extends life span of female SHR mice". Cell Cycle 7 (17): 2769–73. September 2008. doi:10.4161/cc.7.17.6625. PMID 18728386. 
  75. "FOXO3A genotype is strongly associated with human longevity". Proceedings of the National Academy of Sciences of the United States of America 105 (37): 13987–92. September 2008. doi:10.1073/pnas.0801030105. PMID 18765803. Bibcode2008PNAS..10513987W. 
  76. "Association of FOXO3A variation with human longevity confirmed in German centenarians". Proceedings of the National Academy of Sciences of the United States of America 106 (8): 2700–5. February 2009. doi:10.1073/pnas.0809594106. PMID 19196970. Bibcode2009PNAS..106.2700F. 
  77. "Recent advances in understanding the role of FOXO3". F1000Research 7: 1372. 31 August 2018. doi:10.12688/f1000research.15258.1. PMID 30228872. 
  78. "Multivariate genomic scan implicates novel loci and haem metabolism in human ageing". Nature Communications 11 (1): 3570. July 2020. doi:10.1038/s41467-020-17312-3. PMID 32678081. Bibcode2020NatCo..11.3570T. 
  79. "Association of common genetic variation in the insulin/IGF1 signaling pathway with human longevity". Aging Cell 8 (4): 460–72. August 2009. doi:10.1111/j.1474-9726.2009.00493.x. PMID 19489743. 
  80. "Rapamycin fed late in life extends lifespan in genetically heterogeneous mice". Nature 460 (7253): 392–5. July 2009. doi:10.1038/nature08221. PMID 19587680. Bibcode2009Natur.460..392H. 
  81. "A Special Mprize Award". Fight Aging!. 5 October 2009. 
  82. Kanfi, Yariv et al. (22 February 2012). "The sirtuin SIRT6 regulates lifespan in male mice". Nature 483 (7388): 218–21. doi:10.1038/nature10815. PMID 22367546. Bibcode2012Natur.483..218K. 
  83. Carlos López-Otín, Maria A. Blasco, Linda Partridge, Manuel Serrano, Guido Kroemer (6 June 2013). "The Hallmarks of Aging". Cell 153 (6): 1194–1217. doi:10.1016/j.cell.2013.05.039. PMID 23746838. 
  84. Satoh, Akiko et al. (3 September 2013). "Sirt1 Extends Life Span and Delays Aging in Mice through the Regulation of Nk2 Homeobox 1 in the DMH and LH". Cell Metabolism 18 (3): 416–430. doi:10.1016/j.cmet.2013.07.013. PMID 24011076. 
  85. "Google announces Calico, a new company focused on health and well-being". News from Google. 18 September 2013. 
  86. Regalado, Antonio (15 December 2016). "Can naked mole rats teach us the secrets to living longer?". MIT Technology Review. 
  87. Naughton, John (9 April 2017). "Why Silicon Valley wants to thwart the grim reaper". The Guardian. 
  88. Fortuna, W. Harry (8 October 2017). "Seeking eternal life, Silicon Valley is solving for death". Quartz. 
  89. Mitchell, Sarah J; Martin-Montalvo, Alejandro; Mercken, Evi M et al. (27 February 2014). "The SIRT1 Activator SRT1720 Extends Lifespan and Improves Health of Mice Fed a Standard Diet". Cell Reports 6 (5): 836–843. doi:10.1016/j.celrep.2014.01.031. PMID 24582957. 
  90. Mercken, Evi M; Mitchell, Sarah J; Martin-Montalvo, Alejandro et al. (16 June 2014). "SRT2104 extends survival of male mice on a standard diet and preserves bone and muscle mass". Aging Cell 13 (5): 787–796. doi:10.1111/acel.12220. PMID 24931715. 
  91. Zhavoronkov, Alexander; Bhupinder, Bhullar (4 October 2015). "Classifying aging as a disease in the context of ICD-11". Frontiers in Genetics 6: 326. doi:10.3389/fgene.2015.00326. PMID 26583032. 
  92. Stambler, Ilia (1 October 2017). "Recognizing Degenerative Aging as a Treatable Medical Condition: Methodology and Policy". Aging and Disease 8 (5): 583–589. doi:10.14336/AD.2017.0130. PMID 28966803. PMC 5614323. 
  93. "Opening the door to treating ageing as a disease". The Lancet Diabetes & Endocrinology 6 (8): 587. 1 August 2018. doi:10.1016/S2213-8587(18)30214-6. PMID 30053981. 
  94. Calimport, Stuart et al. (1 October 2019). "To help aging populations, classify organismal senescence". Science 366 (6465): 576–578. doi:10.1126/science.aay7319. PMID 31672885. Bibcode2019Sci...366..576C. 
  95. Khaltourina, Daria; Matveyev, Yuri; Alekseev, Aleksey; Cortese, Franco; Ioviţă, Anca (July 2020). "Aging Fits the Disease Criteria of the International Classification of Diseases". Mechanisms of Ageing and Development 189: 111230. doi:10.1016/j.mad.2020.111230. PMID 32251691. 
  96. Zhang, Hongbo; Ryu, Dongryeol; Wu, Yibo; Gariani, Karim; Wang, Xu; Luan, Peiling; D'Amico, Davide; Ropelle, Eduardo R et al. (17 June 2016). "NAD+ repletion improves mitochondrial and stem cell function and enhances life span in mice". Science 352 (6292): 1436–1443. doi:10.1126/science.aaf2693. PMID 27127236. Bibcode2016Sci...352.1436Z. 
  97. Yoshino, Jun; Mills, Kathryn F.; Yoon, Myeong Jin; Imai, Shin-ichiro (15 October 2011). "Nicotinamide mononucleotide, a key NAD+ intermediate, treats the pathophysiology of diet- and age-induced diabetes in mice". Cell Metabolism 14 (4): 528–536. doi:10.1016/j.cmet.2011.08.014. PMID 21982712. 
  98. "What is NMN?". 5 May 2020. 
  99. Strong, Randy; Miller, Richard A et al. (16 June 2016). "Longer lifespan in male mice treated with a weakly estrogenic agonist, an antioxidant, an α‐glucosidase inhibitor or a Nrf2‐inducer". Aging Cell 15 (5): 872–884. doi:10.1111/acel.12496. PMID 27312235. 
  100. Boominathan, Amutha et al. (4 September 2016). "Stable nuclear expression of ATP8 and ATP6 genes rescues a mtDNA Complex V null mutant". Nucleic Acids Research 44 (19): 9342–9357. doi:10.1093/nar/gkw756. PMID 27596602. 
  101. Weintraub, Karen. "Aging Is Reversible—at Least in Human Cells and Live Mice" (in en). Scientific American. 
  102. "Old human cells rejuvenated with stem cell technology" (in sm). News Center. 
  103. Ocampo, Alejandro; Reddy, Pradeep; Martinez-Redondo, Paloma; Platero-Luengo, Aida; Hatanaka, Fumiyuki; Hishida, Tomoaki; Li, Mo; Lam, David et al. (15 December 2016). "In Vivo Amelioration of Age-Associated Hallmarks by Partial Reprogramming" (in English). Cell 167 (7): 1719–1733.e12. doi:10.1016/j.cell.2016.11.052. ISSN 0092-8674. PMID 27984723. 
  104. Ben-Avraham, Danny; Govindaraju, Diddahally R.; Budagov, Temuri; Fradin, Delphine; Durda, Peter et al. (2 June 2017). "The GH receptor exon 3 deletion is a marker of male-specific exceptional longevity associated with increased GH sensitivity and taller stature". Science Advances 3 (6): e1602025. doi:10.1126/sciadv.1602025. PMID 28630896. Bibcode2017SciA....3E2025B. 
  105. "The Nobel Prize in Physiology or Medicine 2018". 
  106. The Lancet Diabetes & Endocrinology (1 August 2018). "Opening the door to treating ageing as a disease". The Lancet Diabetes & Endocrinology 6 (8): 587. doi:10.1016/S2213-8587(18)30214-6. PMID 30053981. 
  107. Biogerontology Research Foundation (2 July 2018). "World Health Organization adds extension code for 'aging-related' via ICD-11". EurekAlert. 
  108. Steve Hill (31 August 2018). "Getting Aging Classified as a Disease – Daria Khaltourina". 
  109. "Inching Towards the Regulatory Classification of Aging as a Disease". 3 September 2018. 
  110. Oksana Andreiuk (12 September 2018). "Let's talk about the World Health Organisation recognising ageing as a disease risk factor, updating the ICD for the first time in 35 years.". 
  111. "MDI Biological Scientists Identify Pathways That Extend Lifespan by 500 Percent". MDI Biological Laboratory. 8 January 2020. 
  112. Michael Irving (8 January 2020). "Worm lifespans extended 500 percent in surprising new aging study". New Atlas. 
  113. Kristin Houser (9 January 2020). "Scientists Extend Lifespan of Worms by 500 Percent". 
  114. Stephen Johnson (13 January 2020). "Biologists extend worm lifespan by 500% in surprising discovery on aging". Big Think. 
  115. "Mayo researchers demonstrate senescent cell burden is reduced in humans by senolytic drugs". Mayo Clinic. Mayo Clinic. 18 September 2019. 
  116. "Senolytics decrease senescent cells in humans: Preliminary report from a clinical trial of Dasatinib plus Quercetin in individuals with diabetic kidney disease". EBioMedicine. EBioMedicine. 20 September 2019. 
  117. "Fruit flies live longer with combination drug treatment". University College London. 30 September 2019. 
  118. Castillo-Quan, Jorge Iván; Tain, Luke S.; Kinghorn, Kerri J.; Li, Li; Grönke, Sebastian; Hinze, Yvonne; Blackwell, T. Keith; Bjedov, Ivana et al. (15 October 2019). "A triple drug combination targeting components of the nutrient-sensing network maximizes longevity". Proceedings of the National Academy of Sciences 116 (42): 20817–20819. doi:10.1073/pnas.1913212116. PMID 31570569. 
  119. "In a first, scientists pinpoint neural activity's role in human longevity". Science Daily. 16 October 2019. 
  120. Zullo, Joseph M.; Drake, Derek; Aron, Liviu; O’Hern, Patrick; Dhamne, Sameer C.; Davidsohn, Noah; Mao, Chai-An; Klein, William H. et al. (October 2019). "Regulation of lifespan by neural excitation and REST" (in en). Nature 574 (7778): 359–364. doi:10.1038/s41586-019-1647-8. ISSN 1476-4687. PMID 31619788. Bibcode2019Natur.574..359Z. 
  121. "Could cytotoxic T-cells be a key to longevity?". Science Daily. 13 November 2019. 
  122. Hashimoto, Kosuke; Kouno, Tsukasa; Ikawa, Tomokatsu; Hayatsu, Norihito; Miyajima, Yurina; Yabukami, Haruka; Terooatea, Tommy; Sasaki, Takashi et al. (26 November 2019). "Single-cell transcriptomics reveals expansion of cytotoxic CD4 T cells in supercentenarians". Proceedings of the National Academy of Sciences 116 (48): 24242–24251. doi:10.1073/pnas.1907883116. PMID 31719197. 
  123. "Blood iron levels could be key to slowing ageing, gene study shows" (in en). 
  124. Timmers, Paul R. H. J.; Wilson, James F.; Joshi, Peter K.; Deelen, Joris (16 July 2020). "Multivariate genomic scan implicates novel loci and haem metabolism in human ageing" (in en). Nature Communications 11 (1): 3570. doi:10.1038/s41467-020-17312-3. ISSN 2041-1723. PMID 32678081. Bibcode2020NatCo..11.3570T. 
  125. "Brain benefits of exercise can be gained with a single protein" (in en). Retrieved 18 August 2020. 
  126. Horowitz, Alana M.; Fan, Xuelai; Bieri, Gregor; Smith, Lucas K.; Sanchez-Diaz, Cesar I.; Schroer, Adam B.; Gontier, Geraldine; Casaletto, Kaitlin B. et al. (10 July 2020). "Blood factors transfer beneficial effects of exercise on neurogenesis and cognition to the aged brain" (in en). Science 369 (6500): 167–173. doi:10.1126/science.aaw2622. ISSN 0036-8075. PMID 32646997. Bibcode2020Sci...369..167H. 
  127. "Researchers discover 2 paths of aging and new insights on promoting healthspan" (in en). 
  128. Li, Yang; Jiang, Yanfei; Paxman, Julie; O'Laughlin, Richard; Klepin, Stephen; Zhu, Yuelian; Pillus, Lorraine; Tsimring, Lev S. et al. (2020). "A programmable fate decision landscape underlies single-cell aging in yeast". Science 369 (6501): 325–329. doi:10.1126/science.aax9552. PMID 32675375. Bibcode2020Sci...369..325L. 
  129. Eisenstein, Michael (19 January 2022). "Rejuvenation by controlled reprogramming is the latest gambit in anti-aging" (in en). Nature Biotechnology 40 (2): 144–146. doi:10.1038/d41587-022-00002-4. PMID 35046614. Retrieved 22 March 2022. 
  130. "Stem cell technique winds back aging in human cells". New Atlas. 25 March 2020. 
  131. Wade, Nicholas (24 March 2020). "Turning Back the Clock on Aging Cells". The New York Times. 
  132. Sarkar, Tapash Jay; Quarta, Marco; Mukherjee, Shravani; Colville, Alex; Paine, Patrick; Doan, Linda; Tran, Christopher M.; Chu, Constance R. et al. (24 March 2020). "Transient non-integrative expression of nuclear reprogramming factors promotes multifaceted amelioration of aging in human cells" (in en). Nature Communications 11 (1): 1545. doi:10.1038/s41467-020-15174-3. ISSN 2041-1723. PMID 32210226. Bibcode2020NatCo..11.1545S. 
  133. "Scientists reverse age-related vision loss, eye damage from glaucoma in mice". Scienmag: Latest Science and Health News. 
  134. Lu, Yuancheng; Brommer, Benedikt; Tian, Xiao; Krishnan, Anitha; Meer, Margarita; Wang, Chen; Vera, Daniel L.; Zeng, Qiurui et al. (December 2020). "Reprogramming to recover youthful epigenetic information and restore vision" (in en). Nature 588 (7836): 124–129. doi:10.1038/s41586-020-2975-4. ISSN 1476-4687. PMID 33268865. Bibcode2020Natur.588..124L. 
  135. "Study reveals immune driver of brain aging" (in en). 
  136. Minhas, Paras S.; Latif-Hernandez, Amira; McReynolds, Melanie R.; Durairaj, Aarooran S.; Wang, Qian; Rubin, Amanda; Joshi, Amit U.; He, Joy Q. et al. (February 2021). "Restoring metabolism of myeloid cells reverses cognitive decline in ageing" (in en). Nature 590 (7844): 122–128. doi:10.1038/s41586-020-03160-0. ISSN 1476-4687. PMID 33473210. Bibcode2021Natur.590..122M. 
  137. "Study: Specific diet, lifestyle interventions may reverse epigenetic aging in healthy adult males" (in en). 28 May 2021. 
  138. Fitzgerald, K. N.; Hodges, R.; Hanes, D.; Stack, E.; Cheishvili, D.; Szyf, M.; Henkel, J.; Twedt, M. W. et al. (2021). Aging. 13. pp. 9419–9432. doi:10.18632/aging.202913. PMID 33844651. PMC 8064200. Retrieved 28 June 2021. 
  139. "Scientists find mechanism that eliminates senescent cells" (in en). 
  140. Arora, Shivani; Thompson, Peter J.; Wang, Yao; Bhattacharyya, Aritra; Apostolopoulou, Hara; Hatano, Rachel; Naikawadi, Ram P.; Shah, Ajit et al. (10 May 2021). "Invariant natural killer T cells coordinate removal of senescent cells" (in English). Med 2 (8): 938–950.e8. doi:10.1016/j.medj.2021.04.014. ISSN 2666-6359. PMID 34617070. 
  141. "Tool that calculates immune system age could predict frailty and disease". New Atlas. 13 July 2021. 
  142. Sayed, Nazish; Huang, Yingxiang; Nguyen, Khiem; Krejciova-Rajaniemi, Zuzana; Grawe, Anissa P.; Gao, Tianxiang; Tibshirani, Robert; Hastie, Trevor et al. (July 2021). "An inflammatory aging clock (iAge) based on deep learning tracks multimorbidity, immunosenescence, frailty and cardiovascular aging" (in en). Nature Aging 1 (7): 598–615. doi:10.1038/s43587-021-00082-y. ISSN 2662-8465. PMID 34888528. 
  143. "Clues to healthy aging found in the gut bacteria of centenarians". New Atlas. 2 August 2021. 
  144. Sato, Yuko et al. (29 July 2021). "Novel bile acid biosynthetic pathways are enriched in the microbiome of centenarians" (in en). Nature 599 (7885): 458–464. doi:10.1038/s41586-021-03832-5. ISSN 1476-4687. PMID 34325466. Bibcode2021Natur.599..458S. 
  145. "Researchers identify new genes linked to longer reproductive lifespan in women" (in en). 
  146. Ruth, Katherine S. et al. (August 2021). "Genetic insights into biological mechanisms governing human ovarian ageing" (in en). Nature 596 (7872): 393–397. doi:10.1038/s41586-021-03779-7. ISSN 1476-4687. PMID 34349265. Bibcode2021Natur.596..393R. 
  147. "Gut bacteria from young mice reverse signs of brain aging in old mice". New Atlas. 10 August 2021. 
  148. Boehme, Marcus; Guzzetta, Katherine E.; Bastiaanssen, Thomaz F. S.; van de Wouw, Marcel; Moloney, Gerard M.; Gual-Grau, Andreu; Spichak, Simon; Olavarría-Ramírez, Loreto et al. (August 2021). "Microbiota from young mice counteracts selective age-associated behavioral deficits" (in en). Nature Aging 1 (8): 666–676. doi:10.1038/s43587-021-00093-9. ISSN 2662-8465. 
  149. Lee, Juneyoung; Venna, Venugopal R.; Durgan, David J.; Shi, Huanan; Hudobenko, Jacob; Putluri, Nagireddy; Petrosino, Joseph; McCullough, Louise D. et al. (9 November 2020). "Young versus aged microbiota transplants to germ-free mice: increased short-chain fatty acids and improved cognitive performance". Gut Microbes 12 (1): 1814107. doi:10.1080/19490976.2020.1814107. ISSN 1949-0976. PMID 32897773. 
  150. "Physiology: Fasting may mediate the beneficial effects of calorie restriction in mice | Nature Metabolism | Nature Portfolio". Nature Asia. 
  151. Green, Cara L.; Lamming, Dudley W.; Fontana, Luigi (13 September 2021). "Molecular mechanisms of dietary restriction promoting health and longevity" (in en). Nature Reviews Molecular Cell Biology 23 (1): 56–73. doi:10.1038/s41580-021-00411-4. ISSN 1471-0080. PMID 34518687. 
  152. "Researchers provide a framework to study precision nutrigeroscience" (in en). Buck Institute for Research on Aging. 
  153. Wilson, Kenneth A.; Chamoli, Manish; Hilsabeck, Tyler A.; Pandey, Manish; Bansal, Sakshi; Chawla, Geetanjali; Kapahi, Pankaj (22 September 2021). "Evaluating the beneficial effects of dietary restrictions: A framework for precision nutrigeroscience" (in en). Cell Metabolism 33 (11): 2142–2173. doi:10.1016/j.cmet.2021.08.018. ISSN 1550-4131. PMID 34555343. PMC 8845500. 
  154. O’Keefe, James H.; Torres-Acosta, Noel; O’Keefe, Evan L.; Saeed, Ibrahim M.; Lavie, Carl J.; Smith, Sarah E.; Ros, Emilio (September 2020). "A Pesco-Mediterranean Diet With Intermittent Fasting". Journal of the American College of Cardiology 76 (12): 1484–1493. doi:10.1016/j.jacc.2020.07.049. PMID 32943166. 
  155. "Intermittent fasting makes fruit flies live longer—will it work for people?" (in en). Columbia University Irving Medical Center. 
  156. Ulgherait, Matt; Midoun, Adil M.; Park, Scarlet J.; Gatto, Jared A.; Tener, Samantha J.; Siewert, Julia; Klickstein, Naomi; Canman, Julie C. et al. (October 2021). "Circadian autophagy drives iTRF-mediated longevity" (in en). Nature 598 (7880): 353–358. doi:10.1038/s41586-021-03934-0. ISSN 1476-4687. PMID 34588695. Bibcode2021Natur.598..353U. 
  157. "Grape seed chemical allows mice to live longer by killing aged cells". New Scientist. 
  158. Xu, Qixia; Fu, Qiang; Li, Zi; Liu, Hanxin; Wang, Ying; Lin, Xu; He, Ruikun; Zhang, Xuguang et al. (December 2021). "The flavonoid procyanidin C1 has senotherapeutic activity and increases lifespan in mice" (in en). Nature Metabolism 3 (12): 1706–1726. doi:10.1038/s42255-021-00491-8. ISSN 2522-5812. PMID 34873338. 
  159. "Japanese scientists develop vaccine to eliminate cells behind aging". Japan Times. 12 December 2021. 
  160. "Senolytic vaccination improves normal and pathological age-related phenotypes and increases lifespan in progeroid mice". Nature Aging. 10 December 2021. 
  161. "A $3bn bet on finding the fountain of youth". The Economist. ISSN 0013-0613. 
  162. 162.0 162.1 Fadnes, Lars T.; Økland, Jan-Magnus; Haaland, Øystein A.; Johansson, Kjell Arne (8 February 2022). "Estimating impact of food choices on life expectancy: A modeling study" (in en). PLOS Medicine 19 (2): e1003889. doi:10.1371/journal.pmed.1003889. ISSN 1549-1676. PMID 35134067. 
  163. "Changing your diet could add up to a decade to life expectancy, study finds" (in en). Public Library of Science. 
  164. "Calorie restriction rewires metabolism, immunity for longer health span" (in en). Science Daily. 10 February 2022. 
  165. Spadaro, O.; Youm, Y.; Shchukina, I.; Ryu, S.; Sidorov, S.; Ravussin, A.; Nguyen, K.; Aladyeva, E. et al. (11 February 2022). "Caloric restriction in humans reveals immunometabolic regulators of health span". Science 375 (6581): 671–677. doi:10.1126/science.abg7292. ISSN 0036-8075. PMID 35143297. Bibcode2022Sci...375..671S. 
  166. "Cellular rejuvenation therapy safely reverses signs of aging in mice" (in en-US). Salk Institute. 7 March 2022. 
  167. Browder, Kristen C.; Reddy, Pradeep; Yamamoto, Mako; Haghani, Amin; Guillen, Isabel Guillen; Sahu, Sanjeeb; Wang, Chao; Luque, Yosu et al. (March 2022). "In vivo partial reprogramming alters age-associated molecular changes during physiological aging in mice" (in en). Nature Aging 2 (3): 243–253. doi:10.1038/s43587-022-00183-2. ISSN 2662-8465. 
  168. Kumar, Premranjan; Liu, Chun; Hsu, Jean W.; Chacko, Shaji; Minard, Charles; Jahoor, Farook; Sekhar, Rajagopal V. (March 2021). "Glycine and N‐acetylcysteine (GlyNAC) supplementation in older adults improves glutathione deficiency, oxidative stress, mitochondrial dysfunction, inflammation, insulin resistance, endothelial dysfunction, genotoxicity, muscle strength, and cognition: Results of a pilot clinical trial" (in en). Clinical and Translational Medicine 11 (3): e372. doi:10.1002/ctm2.372. ISSN 2001-1326. PMID 33783984. 
  169. "GlyNAC supplementation extends life span in mice" (in en). Baylor College of Medicine. 
  170. Kumar, Premranjan; Osahon, Ob W.; Sekhar, Rajagopal V. (January 2022). "GlyNAC (Glycine and N-Acetylcysteine) Supplementation in Mice Increases Length of Life by Correcting Glutathione Deficiency, Oxidative Stress, Mitochondrial Dysfunction, Abnormalities in Mitophagy and Nutrient Sensing, and Genomic Damage" (in en). Nutrients 14 (5): 1114. doi:10.3390/nu14051114. ISSN 2072-6643. PMID 35268089. 
  171. "Senolytic drugs boost key protective protein". Mayo Clinic News Network. 15 March 2022. 
  172. Zhu, Yi; Prata, Larissa G. P. Langhi; Gerdes, Erin O. Wissler; Netto, Jair Machado Espindola; Pirtskhalava, Tamar; Giorgadze, Nino; Tripathi, Utkarsh; Inman, Christina L. et al. (1 March 2022). "Orally-active, clinically-translatable senolytics restore α-Klotho in mice and humans" (in English). EBioMedicine 77: 103912. doi:10.1016/j.ebiom.2022.103912. ISSN 2352-3964. PMID 35292270. 
  173. Brouillette, Monique (2022-05-06). "Scientists Claim They Can Make Human Skin Act 30 Years Younger" (in en-US). 
  174. Gill, Diljeet; Parry, Aled; Santos, Fátima; Okkenhaug, Hanneke; Todd, Christopher D; Hernando-Herraez, Irene; Stubbs, Thomas M; Milagre, Inês et al. (8 April 2022). "Multi-omic rejuvenation of human cells by maturation phase transient reprogramming". eLife 11: e71624. doi:10.7554/eLife.71624. ISSN 2050-084X. PMID 35390271. 
  175. "Anti-ageing technique makes skin cells act 30 years younger". New Scientist. 
  176. Gill, Diljeet; Parry, Aled; Santos, Fátima; Okkenhaug, Hanneke; Todd, Christopher D; Hernando-Herraez, Irene; Stubbs, Thomas M; Milagre, Inês et al. (8 April 2022). "Multi-omic rejuvenation of human cells by maturation phase transient reprogramming". eLife 11: e71624. doi:10.7554/eLife.71624. ISSN 2050-084X. PMID 35390271. 
  177. "New article outlines the characteristics of a 'longevity diet': Review of research in animals and humans to identify how nutrition affects aging and healthy lifespan" (in en). ScienceDaily. 
  178. Longo, Valter D.; Anderson, Rozalyn M. (28 April 2022). "Nutrition, longevity and disease: From molecular mechanisms to interventions" (in English). Cell 185 (9): 1455–1470. doi:10.1016/j.cell.2022.04.002. ISSN 0092-8674. PMID 35487190. 
  179. "Cutting calories and eating at the right time of day leads to longer life in mice" (in en). Howard Hughes Medical Institute. 
  180. Acosta-Rodríguez, Victoria; Rijo-Ferreira, Filipa; Izumo, Mariko; Xu, Pin; Wight-Carter, Mary; Green, Carla B.; Takahashi, Joseph S. (10 June 2022). "Circadian alignment of early onset caloric restriction promotes longevity in male C57BL/6J mice". Science 376 (6598): 1192–1202. doi:10.1126/science.abk0297. ISSN 0036-8075. PMID 35511946. 
  181. Yirka, Bob. "Giving an old mouse cerebrospinal fluid from a young mouse improves its memory" (in en). 
  182. "Verjüngung der Gedächtnisleistung von alten Mäusen" (in en). Science Media Centre Germany. 
  183. Iram, Tal; Kern, Fabian; Kaur, Achint; Myneni, Saket; Morningstar, Allison R.; Shin, Heather; Garcia, Miguel A.; Yerra, Lakshmi et al. (May 2022). "Young CSF restores oligodendrogenesis and memory in aged mice via Fgf17" (in en). Nature 605 (7910): 509–515. doi:10.1038/s41586-022-04722-0. ISSN 1476-4687. PMID 35545674. 
  184. "Research may reveal why people can suddenly become frail in their 70s" (in en). The Guardian. 1 June 2022. 
  185. Mitchell, Emily; Spencer Chapman, Michael; Williams, Nicholas; Dawson, Kevin J.; Mende, Nicole; Calderbank, Emily F.; Jung, Hyunchul; Mitchell, Thomas et al. (June 2022). "Clonal dynamics of haematopoiesis across the human lifespan" (in en). Nature 606 (7913): 343–350. doi:10.1038/s41586-022-04786-y. ISSN 1476-4687. PMID 35650442. 
  186. Kolata, Gina (14 July 2022). "As Y Chromosomes Vanish With Age, Heart Risks May Grow". The New York Times. 
  187. Sano, Soichi; Horitani, Keita; Ogawa, Hayato; Halvardson, Jonatan; Chavkin, Nicholas W.; Wang, Ying; Sano, Miho; Mattisson, Jonas et al. (15 July 2022). "Hematopoietic loss of Y chromosome leads to cardiac fibrosis and heart failure mortality" (in en). Science 377 (6603): 292–297. doi:10.1126/science.abn3100. ISSN 0036-8075. PMID 35857592. 
  188. "Exploring the brief use of rapamycin treatment in early adulthood to extend lifespan" (in en). Max Planck Society. 
  189. Juricic, Paula; Lu, Yu-Xuan; Leech, Thomas; Drews, Lisa F.; Paulitz, Jonathan; Lu, Jiongming; Nespital, Tobias; Azami, Sina et al. (29 August 2022). "Long-lasting geroprotection from brief rapamycin treatment in early adulthood by persistently increased intestinal autophagy" (in en). Nature Aging: 1–13. doi:10.1038/s43587-022-00278-w. ISSN 2662-8465. 
  190. Greenwood, Veronique (6 September 2022). "This Jellyfish Can Live Forever. Its Genes May Tell Us How.". The New York Times. 
  191. Pascual-Torner, Maria; Carrero, Dido; Pérez-Silva, José G.; Álvarez-Puente, Diana; Roiz-Valle, David; Bretones, Gabriel; Rodríguez, David; Maeso, Daniel et al. (6 September 2022). "Comparative genomics of mortal and immortal cnidarians unveils novel keys behind rejuvenation" (in en). Proceedings of the National Academy of Sciences 119 (36): e2118763119. doi:10.1073/pnas.2118763119. ISSN 0027-8424. PMID 36037356. 


External links — history of aging research