Life extension
Life extension is the concept of extending the human lifespan, either through incremental improvements in medicine or through radical increases in maximum lifespan beyond its generally-settled biological limit of around 125 years. This field of study has been explored by numerous researchers and advocates, including "life extensionists", "immortalists", and "longevists". These researchers and advocates hypothesize that future advancements 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 state of optimal health and youth. The ethical implications of life extension are a subject of discourse among bioethicists.
The sale of purported anti-aging products, such as supplements and hormone replacement therapy, is a lucrative global industry. For example, the industry that promotes the use of hormones as a treatment for consumers to slow or reverse the aging process in the US market generated about $50 billion of revenue a year in 2009. The use of such hormone products has not been proven to be effective or safe. Similarly, a variety of apps make claims to assist in extending the life of their users, or predicting their lifespans.
Average life expectancy and lifespan
During the process of aging, an organism accumulates damage to its macromolecules, cells, tissues, and organs. Specifically, aging is characterized as and thought to be caused by "genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, and altered intercellular communication." Oxidation damage to cellular contents caused by free radicals is believed to contribute to aging as well.The longest documented human lifespan is 122 years 164 days, the case of Jeanne Calment, who according to records was born in 1875 and died in 1997, whereas the maximum lifespan of a wildtype mouse, commonly used as a model in research on aging, is about three years. Genetic differences between humans and mice that may account for these different aging rates include differences in efficiency of DNA repair, antioxidant defenses, energy metabolism, proteostasis maintenance, and recycling mechanisms such as autophagy.
The average life expectancy in a population is lowered by infant and child mortality, which are frequently linked to infectious diseases or nutrition problems. Later in life, vulnerability to accidents and age-related chronic disease such as cancer or cardiovascular disease play an increasing role in mortality. Extension of life expectancy and lifespan can often be achieved by access to improved medical care, vaccinations, good diet, exercise, and avoidance of hazards such as smoking.
Maximum lifespan is determined by the rate of aging for a species inherent in its genes and by environmental factors. Widely recognized methods of extending maximum lifespan in model organisms such as nematodes, fruit flies, and mice include caloric restriction, gene manipulation, and administration of pharmaceuticals. Another technique uses evolutionary pressures such as breeding from only older members or altering levels of extrinsic mortality.
Some animals such as hydra, planarian flatworms, and certain sponges, corals, and jellyfish do not die of old age and exhibit potential immortality.
History
The extension of life has been a desire of humanity and a mainstay motif in the history of scientific pursuits and ideas throughout history, from the Sumerian Epic of Gilgamesh and the Egyptian Smith medical papyrus, all the way through the Taoists, Ayurveda practitioners, alchemists, hygienists such as Luigi Cornaro, Johann Cohausen and Christoph Wilhelm Hufeland, and philosophers such as Francis Bacon, René Descartes, Benjamin Franklin and Nicolas Condorcet. However, the beginning of the modern period in this endeavor can be traced to the end of the 19th – beginning of the 20th century, to the so-called "fin-de-siècle" period, denoted as an "end of an epoch" and characterized by the rise of scientific optimism and therapeutic activism, entailing the pursuit of life extension. Among the foremost researchers of life extension at this period were the Nobel Prize winning biologist Elie Metchnikoff -- the author of the cell theory of immunity and vice director of Institut Pasteur in Paris, and Charles-Édouard Brown-Séquard -- the president of the French Biological Society and one of the founders of modern endocrinology.Sociologist James Hughes claims that science has been tied to a cultural narrative of conquering death since the Age of Enlightenment. He cites Francis Bacon as an advocate of using science and reason to extend human life, noting Bacon's novel New Atlantis, wherein scientists worked toward delaying aging and prolonging life. Robert Boyle, founding member of the Royal Society, also hoped that science would make substantial progress with life extension, according to Hughes, and proposed such experiments as "to replace the blood of the old with the blood of the young". Biologist Alexis Carrel was inspired by a belief in indefinite human lifespan that he developed after experimenting with cells, says Hughes.
Contemporary
Regulatory and legal struggles between the Food and Drug Administration and the Life Extension organization included seizure of merchandise and court action. In 1991, Saul Kent and Bill Faloon, the principals of the organization, were jailed for four hours and were released on $850,000 bond each. After 11 years of legal battles, Kent and Faloon convinced the US Attorney's Office to dismiss all criminal indictments brought against them by the FDA.In 2003, Doubleday published "The Immortal Cell: One Scientist's Quest to Solve the Mystery of Human Aging," by Michael D. West. West emphasised the potential role of embryonic stem cells in life extension.
Other modern life extensionists include writer Gennady Stolyarov, who insists that death is "the enemy of us all, to be fought with medicine, science, and technology"; transhumanist philosopher Zoltan Istvan, who proposes that the "transhumanist must safeguard one's own existence above all else"; futurist George Dvorsky, who considers aging to be a problem that desperately needs to be solved; and recording artist Steve Aoki, who has been called "one of the most prolific campaigners for life extension".
Scientific research
In 1991, the American Academy of Anti-Aging Medicine was formed. The American Board of Medical Specialties recognizes neither anti-aging medicine nor the A4M's professional standing.In 2003, Aubrey de Grey and David Gobel formed the Methuselah Foundation, which gives financial grants to anti-aging research projects. In 2009, de Grey and several others founded the SENS Research Foundation, a California-based scientific research organization which conducts research into aging and funds other anti-aging research projects at various universities. In 2013, Google announced Calico, a new company based in San Francisco that will harness new technologies to increase scientific understanding of the biology of aging. It is led by Arthur D. Levinson, and its research team includes scientists such as Hal V. Barron, David Botstein, and Cynthia Kenyon. In 2014, biologist Craig Venter founded Human Longevity Inc., a company dedicated to scientific research to end aging through genomics and cell therapy. They received funding with the goal of compiling a comprehensive human genotype, microbiome, and phenotype database.
Aside from private initiatives, aging research is being conducted in university laboratories, and includes universities such as Harvard and UCLA. University researchers have made a number of breakthroughs in extending the lives of mice and insects by reversing certain aspects of aging.
Research
Theoretically, extension of maximum lifespan in humans could be achieved by reducing the rate of aging damage by periodic replacement of damaged tissues, molecular repair or rejuvenation of deteriorated cells and tissues, reversal of harmful epigenetic changes, or the enhancement of enzyme telomerase activity.Research geared towards life extension strategies in various organisms is currently under way at a number of academic and private institutions. Since 2009, investigators have found ways to increase the lifespan of nematode worms and yeast by 10-fold; the record in nematodes was achieved through genetic engineering and the extension in yeast by a combination of genetic engineering and caloric restriction. A 2009 review of longevity research noted: "Extrapolation from worms to mammals is risky at best, and it cannot be assumed that interventions will result in comparable life extension factors. Longevity gains from dietary restriction, or from mutations studied previously, yield smaller benefits to Drosophila than to nematodes, and smaller still to mammals. This is not unexpected, since mammals have evolved to live many times the worm's lifespan, and humans live nearly twice as long as the next longest-lived primate. From an evolutionary perspective, mammals and their ancestors have already undergone several hundred million years of natural selection favoring traits that could directly or indirectly favor increased longevity, and may thus have already settled on gene sequences that promote lifespan. Moreover, the very notion of a "life-extension factor" that could apply across taxa presumes a linear response rarely seen in biology."
Anti-aging/life-extension drugs
There are numerous chemicals intended to slow the aging process under study in animal models. One type of research is related to the observed effects of a calorie restriction diet, which has been shown to extend lifespan in some animals. Based on that research, there have been attempts to develop drugs that will have the same effect on the aging process as a CR diet, which are known as caloric restriction mimetic drugs, such as rapamycin and metformin.Sirtuin activating polyphenols, such as resveratrol and pterostilbene, and flavonoids, such as quercetin and fisetin, as well as oleic acid are dietary supplements that have also been studied in this context. Other common supplements with less clear biological pathways to target aging include lipoic acid, senolytics, and coenzyme Q10.
While agents such as these have some limited laboratory evidence of efficacy in animals, there are no studies to date in humans for drugs that may promote life extension, mainly because research investment remains at a low level, and regulatory standards are high. Aging is not recognized as a preventable condition by governments, indicating there is no clear pathway to approval of anti-aging medications. Further, anti-aging drug candidates are under constant review by regulatory authorities like the US Food and Drug Administration, which stated in 2023 that "no medication has been proven to slow or reverse the aging process."
LDL-C lowering drugs such as statins and PCSK9 inhibitors present with some of the most promising candidates for increasing lifespan since there is substantial randomized genetic and clinical evidence that reduced risk of atherosclerotic cardiovascular disease via reducing LDL-C would yield a net gain in lifespan.