This timeline lists notable events in the history of research into senescence or biological aging, including the research and development of life extension methods, brain aging delay methods and rejuvenation.
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 BCE), in his Aphorisms , and Aristotle (384 – 322 BCE), 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.
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.
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.
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 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.
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Research domains related or part of senescence research currently not fully included in the timeline:
Notable events in these fields of research that relate to life extension and healthspan are currently deliberately not included in this timeline
Mitochondrial DNA is the DNA located in the mitochondria organelles in a eukaryotic cell that converts chemical energy from food into adenosine triphosphate (ATP). Mitochondrial DNA is a small portion of the DNA contained in a eukaryotic cell; most of the DNA is in the cell nucleus, and, in plants and algae, the DNA also is found in plastids, such as chloroplasts.
Senescence or biological aging is the gradual deterioration of functional characteristics in living organisms. Whole organism senescence involves an increase in death rates and/or a decrease in fecundity with increasing age, at least in the later part of an organism's life cycle. However, the resulting effects of senescence can be delayed. The 1934 discovery that calorie restriction can extend lifespans by 50% in rats, the existence of species having negligible senescence, and the existence of potentially immortal organisms such as members of the genus Hydra have motivated research into delaying senescence and thus age-related diseases. Rare human mutations can cause accelerated aging diseases.
Life extension is the concept of extending the human lifespan, either modestly through improvements in medicine or dramatically by increasing the maximum lifespan beyond its generally-settled biological limit of around 125 years. Several researchers in the area, along with "life extensionists", "immortalists", or "longevists", postulate that future breakthroughs in tissue rejuvenation, stem cells, regenerative medicine, molecular repair, gene therapy, pharmaceuticals, and organ replacement will eventually enable humans to have indefinite lifespans through complete rejuvenation to a healthy youthful condition (agerasia). The ethical ramifications, if life extension becomes a possibility, are debated by bioethicists.
Longevity may refer to especially long-lived members of a population, whereas life expectancy is defined statistically as the average number of years remaining at a given age. For example, a population's life expectancy at birth is the same as the average age at death for all people born in the same year.
Maximum life span is a measure of the maximum amount of time one or more members of a population have been observed to survive between birth and death. The term can also denote an estimate of the maximum amount of time that a member of a given species could survive between birth and death, provided circumstances that are optimal to that member's longevity.
Leonard Pershing Guarente is an American biologist best known for his research on life span extension in the budding yeast Saccharomyces cerevisiae, roundworms, and mice. He is a Novartis Professor of Biology at the Massachusetts Institute of Technology.
Growth differentiation factor 11 (GDF11), also known as bone morphogenetic protein 11 (BMP-11), is a protein that in humans is encoded by the growth differentiation factor 11 gene. GDF11 is a member of the Transforming growth factor beta family.
Ageing is the process of becoming older. The term refers mainly to humans, many other animals, and fungi, whereas for example, bacteria, perennial plants and some simple animals are potentially biologically immortal. In a broader sense, ageing can refer to single cells within an organism which have ceased dividing, or to the population of a species.
The DNA damage theory of aging proposes that aging is a consequence of unrepaired accumulation of naturally occurring DNA damage. Damage in this context is a DNA alteration that has an abnormal structure. Although both mitochondrial and nuclear DNA damage can contribute to aging, nuclear DNA is the main subject of this analysis. Nuclear DNA damage can contribute to aging either indirectly or directly.
Negligible senescence is a term coined by biogerontologist Caleb Finch to denote organisms that do not exhibit evidence of biological aging (senescence), such as measurable reductions in their reproductive capability, measurable functional decline, or rising death rates with age. There are many species where scientists have seen no increase in mortality after maturity. This may mean that the lifespan of the organism is so long that researchers' subjects have not yet lived up to the time when a measure of the species' longevity can be made. Turtles, for example, were once thought to lack senescence, but more extensive observations have found evidence of decreasing fitness with age.
DAF-16 is the sole ortholog of the FOXO family of transcription factors in the nematode Caenorhabditis elegans. It is responsible for activating genes involved in longevity, lipogenesis, heat shock survival and oxidative stress responses. It also protects C.elegans during food deprivation, causing it to transform into a hibernation - like state, known as a Dauer. DAF-16 is notable for being the primary transcription factor required for the profound lifespan extension observed upon mutation of the insulin-like receptor DAF-2. The gene has played a large role in research into longevity and the insulin signalling pathway as it is located in C. elegans, a successful ageing model organism.
Genetics of aging is generally concerned with life extension associated with genetic alterations, rather than with accelerated aging diseases leading to reduction in lifespan.
A senolytic is among a class of small molecules under basic research to determine if they can selectively induce death of senescent cells and improve health in humans. A goal of this research is to discover or develop agents to delay, prevent, alleviate, or reverse age-related diseases. Removal of senescent cells with senolytics has been proposed as a method of enhancing immunity during aging.
Jan Vijg is the Lola and Saul Kramer Chairperson in Molecular Genetics at the Department of Genetics at the Albert Einstein College of Medicine, New York City, United States. Prior to this appointment, he was a professor at the Buck Institute for Research on Aging.
BioViva is an American biotechnology gene therapy company, based in Bainbridge Island, Washington, researching treatments to interfere in the aging process in humans.
In biogerontology, the disposable soma theory of aging states that organisms age due to an evolutionary trade-off between growth, reproduction, and DNA repair maintenance. Formulated by British biologist Thomas Kirkwood, the disposable soma theory explains that an organism only has a limited amount of resources that it can allocate to its various cellular processes. Therefore, a greater investment in growth and reproduction would result in reduced investment in DNA repair maintenance, leading to increased cellular damage, shortened telomeres, accumulation of mutations, compromised stem cells, and ultimately, senescence. Although many models, both animal and human, have appeared to support this theory, parts of it are still controversial. Specifically, while the evolutionary trade-off between growth and aging has been well established, the relationship between reproduction and aging is still without scientific consensus, and the cellular mechanisms largely undiscovered.
Young blood transfusion refers to transfusing blood specifically from a young person into an older one with the intention of creating a health benefit. The efficacy and safety of young blood transfusions for anti-aging purposes remain a subject of debate in the scientific community, with limited clinical evidence in humans. There are also concerns of harm. While some preclinical studies on animals suggest potential benefits, there is a lack of robust clinical evidence to support its use in humans. The U.S. Food and Drug Administration, in 2019, cautioned "consumers against receiving young donor plasma infusions" stating that they are an "unproven treatment".
The mitochondrial theory of ageing has two varieties: free radical and non-free radical. The first is one of the variants of the free radical theory of ageing. It was formulated by J. Miquel and colleagues in 1980 and was developed in the works of Linnane and coworkers (1989). The second was proposed by A. N. Lobachev in 1978.
Thomas A. Rando is an American stem cell biologist and neurologist, best known for his research on basic mechanisms of stem cell biology and the biology of aging. He is the Director of the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research and a professor of Neurology and Molecular, Cell and Developmental Biology at the University of California, Los Angeles. Prior to joining the UCLA faculty, he served as Professor of Neurology and Neurological Sciences at Stanford University School of Medicine, where he was also founding director of the Glenn Center for the Biology of Aging. His additional roles while at Stanford included co-founder and deputy director of the Stanford Center on Longevity, founding director of Stanford's Muscular Dystrophy Association Clinic, and Chief of Neurology at the VA Palo Alto Health Care System.
Aging is characterized by a progressive loss of physiological integrity, leading to impaired function and increased vulnerability to death. The hallmarks of aging are the types of biochemical changes that occur in all organisms that experience biological aging and lead to a progressive loss of physiological integrity, impaired function and, eventually, death. They were first listed in a landmark paper in 2013 to conceptualize the essence of biological aging and its underlying mechanisms.
These clocks were meant to be used by researchers to test the antiaging effects of drugs or lifestyle changes in animals or people. Indeed, studies have shown that people who test as biologically older than their chronological age are at increased risk of certain diseases and death. But companies have since sprung up to make clocks of their own or adapt existing ones into direct-to-consumer tests.