Timeline of senescence research

From Wikipedia, the free encyclopedia

This timeline lists notable events in the history of research of senescence or biological aging. People have always been interested in how to make their lives longer and healthier in old age. Already 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 expresses 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 achievements of the earlier generations about this issue.[1][2][3]

Background[]

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 expecancy 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.

Timeline[]

Search for an elixir of youth in ancient times[]

  • 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 saw that the person is 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.[10] 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 problems with health. But changing his lifestyle he was able to live till 98 years (1467–1566).[11] (Though it is possible that he increase 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 of 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.
  • 1882 August Weismann puts forward the first version of wear and tear theory of aging.[12][13] It can be considered the first scientific theory why organisms are aging.
  • 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][14][15][11]
  • 1903 Ilya Mechnikov coined the term "gerontology".[16][17][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.[14][15] In 1908 Mechnikov received the Nobel Prize for his work on immunology (adjacent area of his research).[18] Adhering to his diet, Mechnikov lived a very long life compared to his short-lived relatives.[19]
  • 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).[11] 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][20] 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.[14][15][21][22][23]
  • 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[24]), 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.[14][15]
  • 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.[11] 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.[14][15] 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 espicially 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][15] 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][14] 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).[14][15] 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).[25]
  • 1933 The first institute in the world dedicated to study of aging. It was created in Kishinev (at that time 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.[26]
  • 1934 The first widely known scientific publication on the impact of dietary restriction on life expectancy, authored by Clive McCay.[27][28][29] 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,[30] 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.[26]
  • 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][14][15] The serum of Bogomolets was actively used in Soviet hospitals during WWII. For his work, Alexander Bogomolets received in 1941 the Stalin Prize,[31] 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  [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.[32]
  • 1938 The world's first scientific conference on aging and longevity in 1938 in Kiev, that was convened by Alexander Bogomolets.[1][33]
  • 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 WWII, 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.

  • 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]
  • 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.[35][36][37]
  • 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.[43]
  • 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.[44][45] This research is based on the theoretical works of Alexey Olovnikov.[45][46][47] 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,[48] in the same year Alexey Olovnikov was awarded the Demidov Prize.[49]
  • 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.[54]
  • 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.[55]
  • 1995 Method for detection of senescent cells using a cytochemical assay.[56]
  • 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.
  • 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 form passive study of aging and building theories to attempts to interfere in the process to extend 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 granting aging an official status of a disease, and about the possibility of mass testing on human volunteers.

  • 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.[59]
  • 2004 Aubrey de Grey coined the term "longevity escape velocity" (LEV).[61] 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[62]).
  • 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.[63]
  • 2004 Creation of the first curated database of genes related to human ageing: .[64]
  • 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.[65][66][67] In 2012, Shinya Yamanaka and John Gurdon received the Nobel Prize for their work on reprogramming mature cells into pluripotent cells.[68]
  • 2007 Extension of mouse lifespan via deletion of insulin receptor in the brain.[27][69]
  • 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.[27][70]
  • 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.[71][72][73][74]
  • 2009 Association of genetic variants in insulin/IGF1 signaling with human longevity.[27][75]
  • 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.[27][76][77]
  • 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).
  • 2012 It was discovered that protein Sirtuin 6 (SIRT6) regulates the lifespan of male mice (but not female mice).[27][78]
  • 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.[79]
  • 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.[27][80]
  • 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.[81][82][83][84]
  • 2014 First evidence that pharmacological activation of SIRT1 extends lifespan in mice and improves their health.[27][85][86]
  • 2010s second half The emergence of official discussions about the possibility of recognizing aging as a disease.[87][88][89][90][91]
  • 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.[27][92] One of these NAD+ precursor molecules is NMN.[93][94]
  • 2016 Demonstration that a combination of longevity associated drugs can additively extend lifespan, at least in mice.[27][95]
  • 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.[96]
  • 2016 Sientists show that expressing reprogramming factors in mice with premature aging can extend their lifespan by about 20%.[97][98][99]
  • 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.[27][100]
  • 2018 The Nobel Prize for cancer research was awarded to James Allison and Tasuku Honjo.[101] (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.[102][103][104][105][106]

2019[]

  • 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.[107][108][109][110]
  • 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.[111][112]
  • 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.[115][116]

2020[]

  • 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.[124][125]
  • 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.[126][127]
  • A study shows that reprogramming induced with the OSK-genes can restore youthful epigenetic patterns as well as revert age-related vision loss.[128][129]

2021[]

  • A randomized clinical trial demonstrates that a combination therapy of a short (two months) intervention of diet, phytonutrient and probiotics supplementation, exercise, relaxation and further lifestyle changes can lead to substantial decrease of the Horvath DNAmAge Epigenetic clock epigenetic aging biomarker in healthy adults and that such may therefore be, measurable, DNA methylome rejuvenation guidance.[132][133]
  • Scientists report alternative approach to senolytics for removing senescent cells: invariant NKT (iNKT) cells.[134][135]
  • Scientists demonstrate a tool to calculate a person's inflammatory age (iAge) based on patterns of systemic age-related inflammation and identify cytokine CXCL9 as a key suppression target.[136][137]
  • A study indicates gut microbiomes with large amounts of microbes capable of generating unique secondary bile acids are a key element of centenarians' longevity.[138][139]

See also[]

Fields
Extraterrestrial environment
Terrestrial environment
Other/related
  • History of technology by type
  • List of science timelines

Excluded fields of research[]

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

  • Nutritional science#History –
  • Health#Maintaining – conventional ways of maintaining health for life extension
    • Exercise#Health effects
    • Neurobiological effects of physical exercise

References[]

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Literature[]

External links[]

www.longevityhistory.com — history of aging research

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