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Wikipedia

Life extension

February 15, 2024

For other uses, see Life extension (disambiguation).

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 limit of 125 years.[1] Several researchers in the area, along with "life extensionists", "immortalists", or "longevists" (those who wish to achieve longer lives themselves), postulate that future breakthroughs in tissue rejuvenation, stem cells, regenerative medicine, molecular repair, gene therapy, pharmaceuticals, and organ replacement (such as with artificial organs or xenotransplantations) will eventually enable humans to have indefinite lifespans through complete rejuvenation to a healthy youthful condition (agerasia[2]). The ethical ramifications, if life extension becomes a possibility, are debated by bioethicists.

The sale of purported anti-aging products such as supplements and hormone replacement 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.[3] The use of such hormone products has not been proven to be effective or safe.[3][4][5][6]

Average life expectancy and lifespan edit

Main article: Senescence

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."[7] Oxidation damage to cellular contents caused by free radicals is believed to contribute to aging as well.[8][9]

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.[10] 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.[11]

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.[12] Another technique uses evolutionary pressures such as breeding from only older members or altering levels of extrinsic mortality.[13][14] Some animals such as hydra, planarian flatworms, and certain sponges, corals, and jellyfish do not die of old age and exhibit potential immortality.[15][16][17][18]

Beliefs and methods edit

See also: Ageing § Prevention and delay, and Brain aging

Senolytics and prolongevity drugs edit

See also: Geroprotector and MTOR inhibitors § Rapamycin and rapalogs
This section is an excerpt from Senolytic.[edit]
A senolytic (from the words senescence and -lytic, "destroying") 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.[19] A goal of this research is to discover or develop agents to delay, prevent, alleviate, or reverse age-related diseases.[20][21] A related concept is "senostatic", which means to suppress senescence.[22]

Senolytics eliminate senescent cells whereas senomorphics – with candidates such as Apigenin, Everolimus and Rapamycin – modulate properties of senescent cells without eliminating them, suppressing phenotypes of senescence, including the SASP.[23][24] Senomorphic effects may be one major effect mechanism of a range of prolongevity drug candidates. Such candidates are however typically not studied for just one mechanism, but multiple. There are biological databases of prolongevity drug candidates under research as well as of potential gene/protein targets. These are enhanced by longitudinal cohort studies, electronic health records, computational (drug) screening methods, computational biomarker-discovery methods and computational biodata-interpretation/personalized medicine methods.[25][26][27]

Besides rapamycin and senolytics, the drug-repurposing candidates studied most extensively include metformin, acarbose, spermidine and NAD+ enhancers.[28]

Many prolongevity drugs are synthetic alternatives or potential complements to existing nutraceuticals, such as various sirtuin-activating compounds under investigation like SRT2104.[29] In some cases pharmaceutical administration is combined with that of neutraceuticals – such as in the case of glycine combined with NAC.[30] Often studies are structured based on or thematize specific prolongevity targets, listing both nutraceuticals and pharmaceuticals (together or separately) such as FOXO3-activators.[31]

Researchers are also exploring ways to mitigate side-effects from such substances (possibly most notably rapamycin and its derivatives) such as via protocols of intermittent administration[32][24][23][33][34] and have called for research that helps determine optimal treatment schedules (including timing) in general.[35]

Diets and supplements edit

Vitamins and antioxidants edit

See also: Inflammaging and DNA damage theory of aging

The free-radical theory of aging suggests that antioxidant supplements might extend human life. Reviews, however, have found that use of vitamin A (as β-carotene) and vitamin E supplements possibly can increase mortality.[36][37] Other reviews have found no relationship between vitamin E and other vitamins with mortality.[38] Vitamin D supplementation of various dosages is investigated in trials[39] and there also is research into GlyNAC (see above).[30]

Complications edit

Complications of antioxidant supplementation (especially continuous high dosages far above the RDA) include that reactive oxygen species (ROS), which are mitigated by antioxidants, "have been found to be physiologically vital for signal transduction, gene regulation, and redox regulation, among others, implying that their complete elimination would be harmful". In particular, one way of multiple they can be detrimental is by inhibiting adaptation to exercise such as muscle hypertrophy (e.g. during dedicated periods of caloric surplus).[40][41][42] There is also research into stimulating/activating/fueling endogenous antioxidant generation, in particular e.g. of neutraceutical glycine and pharmaceutical NAC.[43] Antioxidants can change the oxidation status of different e.g. tissues, targets or sites each with potentially different implications, especially for different concentrations.[44][45][46][47] A review suggests mitochondria have a hormetic response to ROS, whereby low oxidative damage can be beneficial.[48]

Dietary restriction edit

Main article: Diet and longevity
See also: Caloric restriction mimetic

As of 2021, there is no clinical evidence that any dietary restriction practice contributes to human longevity.[49]

Healthy diet edit

Research suggests that increasing adherence to Mediterranean diet patterns is associated with a reduction in total and cause-specific mortality, extending health- and lifespan.[50][51][52][53] Research is identifying the key beneficial components of the Mediterranean diet.[54][55] Studies suggest dietary changes are a factor of national relative rises in life-span.[56]

Optimal diet edit
See also: Sustainable consumption § Sustainable food consumption

Approaches to develop optimal diets for health- and lifespan (or "longevity diets")[57] include:

Other approaches edit

Further advanced biosciences-based approaches include:

Within the field edit

See also: Biogerontology

There is a need and research into the development of aging biomarkers such as the epigenetic clock "to assess the ageing process and the efficacy of interventions to bypass the need for large-scale longitudinal studies".[77][26] Such biomarkers may also include in vivo brain imaging.[83]

Reviews sometimes include structured tables that provide systematic overviews of intervention/drug candidates with a review calling for integrating "current knowledge with multi-omics, health records, and drug safety data to predict drugs that can improve health in late life" and listing major outstanding questions.[25] Biological databases of prolongevity drug candidates under research as well as of potential gene/protein targets include GenAge, DrugAge and Geroprotectors.[25][84]

A review has pointed out that the approach of "'epidemiological' comparison of how a low versus a high consumption of an isolated macronutrient and its association with health and mortality may not only fail to identify protective or detrimental nutrition patterns but may lead to misleading interpretations". It proposes a multi-pillar approach, and summarizes findings towards constructing – multi-system-considering and at least age-personalized dynamic – refined longevity diets. Epidemiological-type observational studies included in meta-analyses should according to the study at least be complemented by "(1) basic research focused on lifespan and healthspan, (2) carefully controlled clinical trials, and (3) studies of individuals and populations with record longevity".[57]

Hormone treatment edit

The anti-aging industry offers several hormone therapies. Some of these have been criticized for possible dangers and a lack of proven effect. For example, the American Medical Association has been critical of some anti-aging hormone therapies.[3]

While growth hormone (GH) decreases with age, the evidence for use of growth hormone as an anti-aging therapy is mixed and based mostly on animal studies. There are mixed reports that GH or IGF-1 modulates the aging process in humans and about whether the direction of its effect is positive or negative.[85]

Klotho[69][86] and exerkines[74] (see above) like irisin[87] are being investigated for potential pro-longevity therapies.

Lifestyle factors edit

See also: Lifestyle disease

Loneliness/isolation, social life and support,[53][88] exercise/physical activity (partly via neurobiological effects and increased NAD+ levels),[53][89][77][78][90][91] psychological characteristics/personality (possibly highly indirectly),[92][93] sleep duration,[53] circadian rhythms (patterns of sleep, drug-administration and feeding),[94][95][96] type of leisure activities,[53] not smoking,[53] altruistic emotions and behaviors,[97][98] subjective well-being,[99] mood[53] and stress (including via heat shock protein)[53][100] are investigated as potential (modulatable) factors of life extension.

Healthy lifestyle practices and healthy diet have been suggested as "first-line function-preserving strategies, with pharmacological agents, including existing and new pharmaceuticals and novel 'nutraceutical' compounds, serving as potential complementary approaches".[101]

Societal strategies edit

See also: § Ethics and politics, § Scientific research, Clinical trial, Metascience, Telehealth, Health economics, Health education, and Medical research
 
Life expectancy vs healthcare spending of rich OECD countries. US average of $10,447 in 2018.[102]

Collectively, addressing common causes of death could extend lifespans of populations and humanity overall. For instance, a 2020 study indicates that the global mean loss of life expectancy (LLE) from air pollution in 2015 was 2.9 years, substantially more than, for example, 0.3 years from all forms of direct violence, albeit a significant fraction of the LLE (a measure similar to years of potential life lost) is considered to be unavoidable.[103]

Regular screening and doctor visits has been suggested as a lifestyle-societal intervention.[53] (See also: medical test and biomarker)

Health policy and changes to standard healthcare could support the adoption of the field's conclusions – a review suggests that the longevity diet would be a "valuable complement to standard healthcare and that, taken as a preventative measure, it could aid in avoiding morbidity, sustaining health into advanced age" as a form of preventive healthcare.[57]

It has been suggested that in terms of healthy diets, Mediterranean-style diets could be promoted by countries for ensuring healthy-by-default choices ("to ensure the healthiest choice is the easiest choice") and with highly effective measures including dietary education, food checklists and recipes that are "simple, palatable, and affordable".[104]

A review suggests that "targeting the aging process per se may be a far more effective approach to prevent or delay aging-associated pathologies than treatments specifically targeted to particular clinical conditions".[105]

Low ambient temperature edit

Low ambient temperature as a physical factor affecting free radical levels was identified as a treatment producing exceptional lifespan increase in Drosophila melanogaster and other living beings.[106]

History edit

Further information: Timeline of senescence research

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" (end of the century) 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 (or life-extensionism). Among the foremost researchers of life extension at this period were the Nobel Prize winning biologist Elie Metchnikoff (1845-1916) -- the author of the cell theory of immunity and vice director of Institut Pasteur in Paris, and Charles-Édouard Brown-Séquard (1817-1894) -- the president of the French Biological Society and one of the founders of modern endocrinology.[107]

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 (1561–1626) 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 (1627–1691), 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 (1873–1944) was inspired by a belief in indefinite human lifespan that he developed after experimenting with cells, says Hughes.[108]

Regulatory and legal struggles between the Food and Drug Administration (FDA) and the Life Extension organization included seizure of merchandise and court action.[109] 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.[110] 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.[111]

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.[112]

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";[113] transhumanist philosopher Zoltan Istvan, who proposes that the "transhumanist must safeguard one's own existence above all else";[114] futurist George Dvorsky, who considers aging to be a problem that desperately needs to be solved;[115] and recording artist Steve Aoki, who has been called "one of the most prolific campaigners for life extension".[116]

Scientific research edit

See also: Timeline of senescence research

In 1991, the American Academy of Anti-Aging Medicine (A4M) was formed. The American Board of Medical Specialties recognizes neither anti-aging medicine nor the A4M's professional standing.[117]

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.[118] 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.[119] It is led by Arthur D. Levinson,[120] 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.[121]

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.[122][123][124][125]

Ethics and politics edit

Scientific controversy edit

Some critics dispute the portrayal of aging as a disease. For example, Leonard Hayflick, who determined that fibroblasts are limited to around 50 cell divisions, reasons that aging is an unavoidable consequence of entropy. Hayflick and fellow biogerontologists Jay Olshansky and Bruce Carnes have strongly criticized the anti-aging industry in response to what they see as unscrupulous profiteering from the sale of unproven anti-aging supplements.[5]

Consumer motivations edit

Research by Sobh and Martin (2011) suggests that people buy anti-aging products to obtain a hoped-for self (e.g., keeping a youthful skin) or to avoid a feared-self (e.g., looking old). The research shows that when consumers pursue a hoped-for self, it is expectations of success that most strongly drive their motivation to use the product. The research also shows why doing badly when trying to avoid a feared self is more motivating than doing well. When product use is seen to fail it is more motivating than success when consumers seek to avoid a feared-self.[126]

Political parties edit

Though many scientists state[127] that life extension and radical life extension are possible, there are still no international or national programs focused on radical life extension. There are political forces working both for and against life extension. By 2012, in Russia, the United States, Israel, and the Netherlands, the Longevity political parties started. They aimed to provide political support to radical life extension research and technologies, and ensure the fastest possible and at the same time soft transition of society to the next step – life without aging and with radical life extension, and to provide access to such technologies to most currently living people.[128]

Silicon Valley edit

Some tech innovators and Silicon Valley entrepreneurs have invested heavily into anti-aging research. This includes Jeff Bezos (founder of Amazon), Larry Ellison (founder of Oracle), Peter Thiel (former PayPal CEO),[129] Larry Page (co-founder of Google), Peter Diamandis,[130] Sam Altman (CEO of OpenAI, invested in Retro Biosciences), and Brian Armstrong (founder of Coinbase and NewLimit).[131]

Commentators edit

Leon Kass (chairman of the US President's Council on Bioethics from 2001 to 2005) has questioned whether potential exacerbation of overpopulation problems would make life extension unethical.[132] He states his opposition to life extension with the words:

"simply to covet a prolonged life span for ourselves is both a sign and a cause of our failure to open ourselves to procreation and to any higher purpose ... [The] desire to prolong youthfulness is not only a childish desire to eat one's life and keep it; it is also an expression of a childish and narcissistic wish incompatible with devotion to posterity."[133]

John Harris, former editor-in-chief of the Journal of Medical Ethics, argues that as long as life is worth living, according to the person himself, we have a powerful moral imperative to save the life and thus to develop and offer life extension therapies to those who want them.[134]

Transhumanist philosopher Nick Bostrom has argued that any technological advances in life extension must be equitably distributed and not restricted to a privileged few.[135] In an extended metaphor entitled "The Fable of the Dragon-Tyrant", Bostrom envisions death as a monstrous dragon who demands human sacrifices. In the fable, after a lengthy debate between those who believe the dragon is a fact of life and those who believe the dragon can and should be destroyed, the dragon is finally killed. Bostrom argues that political inaction allowed many preventable human deaths to occur.[136]

Overpopulation concerns edit

Controversy about life extension is due to fear of overpopulation and possible effects on society.[137] Biogerontologist Aubrey De Grey counters the overpopulation critique by pointing out that the therapy could postpone or eliminate menopause, allowing women to space out their pregnancies over more years and thus decreasing the yearly population growth rate.[138] Moreover, the philosopher and futurist Max More argues that, given the fact the worldwide population growth rate is slowing down and is projected to eventually stabilize and begin falling, superlongevity would be unlikely to contribute to overpopulation.[137]

Opinion polls edit

A Spring 2013 Pew Research poll in the United States found that 38% of Americans would want life extension treatments, and 56% would reject it. However, it also found that 68% believed most people would want it and that only 4% consider an "ideal lifespan" to be more than 120 years. The median "ideal lifespan" was 91 years of age and the majority of the public (63%) viewed medical advances aimed at prolonging life as generally good. 41% of Americans believed that radical life extension (RLE) would be good for society, while 51% said they believed it would be bad for society.[139] One possibility for why 56% of Americans claim they would reject life extension treatments may be due to the cultural perception that living longer would result in a longer period of decrepitude, and that the elderly in our current society are unhealthy.[140]

Religious people are no more likely to oppose life extension than the unaffiliated,[139] though some variation exists between religious denominations.

Aging as a disease edit

Most mainstream medical organizations and practitioners do not consider aging to be a disease. Biologist David Sinclair says: "I don't see aging as a disease, but as a collection of quite predictable diseases caused by the deterioration of the body."[141] The two main arguments used are that aging is both inevitable and universal while diseases are not.[142] However, not everyone agrees. Harry R. Moody, director of academic affairs for AARP, notes that what is normal and what is disease strongly depend on a historical context.[143] David Gems, assistant director of the Institute of Healthy Ageing, argues that aging should be viewed as a disease.[144] In response to the universality of aging, David Gems notes that it is as misleading as arguing that Basenji are not dogs because they do not bark.[145] Because of the universality of aging he calls it a "special sort of disease". Robert M. Perlman, coined the terms "aging syndrome" and "disease complex" in 1954 to describe aging.[146]

The discussion whether aging should be viewed as a disease or not has important implications. One view is, this would stimulate pharmaceutical companies to develop life extension therapies and in the United States of America, it would also increase the regulation of the anti-aging market by the Food and Drug Administration (FDA). Anti-aging now falls under the regulations for cosmetic medicine which are less tight than those for drugs.[145][147]

Research edit

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.[148][149]

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.[150] 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."[150]

Anti-aging drugs edit

There are a number of chemicals intended to slow the aging process currently being studied in animal models.[151] One type of research is related to the observed effects of a calorie restriction (CR) diet, which has been shown to extend lifespan in some animals.[152] Based on that research, there have been attempts to develop drugs that will have the same effect on the aging process as a caloric restriction diet, which are known as caloric restriction mimetic drugs. Some drugs that are already approved for other uses have been studied for possible longevity effects on laboratory animals because of a possible CR-mimic effect; they include rapamycin for mTOR inhibition[153] and metformin for AMPK activation.[154]

Sirtuin activating polyphenols, such as resveratrol and pterostilbene,[155][156][157] and flavonoids, such as quercetin and fisetin,[158] as well as oleic acid[159] are dietary supplements that have also been studied in this context. Other popular supplements with less clear biological pathways to target aging include, lipoic acid,[160] senolytics such as curcumin,[158] and Coenzyme Q10.[161] Daily low doses of ethanol as a potential supplement in spite of its highly negative hormesis response at higher doses has also been studied.[162]

Other attempts to create anti-aging drugs have taken different research paths. One notable direction of research explores the possibility of lengthening chromosomal telomeres (protective caps at the end of chromosomes) by reactivating telomerase, the enzyme responsible for telomere length maintenance. However, telomerase is virtually unexpressed in normal, healthy somatic cells[163] and there are potential dangers in this approach as research has shown a strong link between telomerase expression and cancer and tumors in somatic (non-germ line) cells.[164][165]

Nanotechnology edit

Future advances in nanomedicine could give rise to life extension through the repair of many processes thought to be responsible for aging. K. Eric Drexler, one of the founders of nanotechnology, postulated cell repair machines, including ones operating within cells and utilizing as yet hypothetical molecular computers, in his 1986 book Engines of Creation. Raymond Kurzweil, a futurist and transhumanist, stated in his book The Singularity Is Near that he believes that advanced medical nanorobotics could completely remedy the effects of aging by 2030.[166] According to Richard Feynman, it was his former graduate student and collaborator Albert Hibbs who originally suggested to him (circa 1959) the idea of a medical use for Feynman's theoretical nanomachines (see biological machine). Hibbs suggested that certain repair machines might one day be reduced in size to the point that it would, in theory, be possible to (as Feynman put it) "swallow the doctor". The idea was incorporated into Feynman's 1959 essay There's Plenty of Room at the Bottom.[167]

Cloning and body part replacement edit

Some life extensionists suggest that therapeutic cloning and stem cell research could one day provide a way to generate cells, body parts, or even entire bodies (generally referred to as reproductive cloning) that would be genetically identical to a prospective patient. Recently, the US Department of Defense initiated a program to research the possibility of growing human body parts on mice.[168] Complex biological structures, such as mammalian joints and limbs, have not yet been replicated. Dog and primate brain transplantation experiments were conducted in the mid-20th century but failed due to rejection and the inability to restore nerve connections. As of 2006, the implantation of bio-engineered bladders grown from patients' own cells has proven to be a viable treatment for bladder disease.[169] Proponents of body part replacement and cloning contend that the required biotechnologies are likely to appear earlier than other life-extension technologies.

The use of human stem cells, particularly embryonic stem cells, is controversial. Opponents' objections generally are based on interpretations of religious teachings or ethical considerations.[170] Proponents of stem cell research point out that cells are routinely formed and destroyed in a variety of contexts. Use of stem cells taken from the umbilical cord or parts of the adult body may not provoke controversy.[171]

The controversies over cloning are similar, except general public opinion in most countries stands in opposition to reproductive cloning. Some proponents of therapeutic cloning predict the production of whole bodies, lacking consciousness, for eventual brain transplantation.

Cyborgs edit

Main article: Cyborg

Replacement of biological (susceptible to diseases) organs with mechanical ones could extend life. This is the goal of the 2045 Initiative.[172]

Cryonics edit

Main article: Cryonics

Cryonics is the low-temperature freezing (usually at −196 °C or −320.8 °F or 77.1 K) of a human corpse, with the hope that resuscitation may be possible in the future.[173][174] It is regarded with skepticism within the mainstream scientific community and has been characterized as quackery.[175]

Strategies for engineered negligible senescence edit

Main articles: Strategies for engineered negligible senescence and Genetics of aging

Another proposed life extension technology aims to combine existing and predicted future biochemical and genetic techniques. SENS proposes that rejuvenation may be obtained by removing aging damage via the use of stem cells and tissue engineering, telomere-lengthening machinery, allotopic expression of mitochondrial proteins, targeted ablation of cells, immunotherapeutic clearance, and novel lysosomal hydrolases.[176]

While some biogerontologists find these ideas "worthy of discussion",[177][178] others contend that the alleged benefits are too speculative given the current state of technology, referring to it as "fantasy rather than science".[4][6]

Genetic editing edit

Main articles: Genetics of aging and Genome editing

Genome editing, in which nucleic acid polymers are delivered as a drug and are either expressed as proteins, interfere with the expression of proteins, or correct genetic mutations, has been proposed as a future strategy to prevent aging.[179][180]

A large array of genetic modifications have been found to increase lifespan in model organisms such as yeast, nematode worms, fruit flies, and mice. As of 2013, the longest extension of life caused by a single gene manipulation was roughly 50% in mice and 10-fold in nematode worms.[181]

 
"Healthspan, parental lifespan, and longevity are highly genetically correlated."[182]

In July 2020 scientists, using public biological data on 1.75 m people with known lifespans overall, identify 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 – and identify haem metabolism as a promising candidate for further research within the field. Their study suggests that high levels of iron in the blood likely reduce, and genes involved in metabolising iron likely increase healthy years of life in humans.[183][182] The same month other 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.[184][185]

Fooling genes edit

In The Selfish Gene, Richard Dawkins describes an approach to life-extension that involves "fooling genes" into thinking the body is young.[186] Dawkins attributes inspiration for this idea to Peter Medawar. The basic idea is that our bodies are composed of genes that activate throughout our lifetimes, some when we are young and others when we are older. Presumably, these genes are activated by environmental factors, and the changes caused by these genes activating can be lethal. It is a statistical certainty that we possess more lethal genes that activate in later life than in early life. Therefore, to extend life, we should be able to prevent these genes from switching on, and we should be able to do so by "identifying changes in the internal chemical environment of a body that take place during aging... and by simulating the superficial chemical properties of a young body".[187]

Mind uploading edit

Main article: Mind uploading

One hypothetical future strategy that, as some suggest,[who?] "eliminates" the complications related to a physical body, involves the copying or transferring (e.g. by progressively replacing neurons with transistors) of a conscious mind from a biological brain to a non-biological computer system or computational device. The basic idea is to scan the structure of a particular brain in detail, and then construct a software model of it that is so faithful to the original that, when run on appropriate hardware, it will behave in essentially the same way as the original brain.[188] Whether or not an exact copy of one's mind constitutes actual life extension is matter of debate.

However, critics argue that the uploaded mind would simply be a clone and not a true continuation of a person's consciousness.[189]

Some scientists believe that the dead may one day be "resurrected" through simulation technology.[190]

Young blood injection edit

Further information: Young blood transfusion

Some clinics currently offer injection of blood products from young donors. The alleged benefits of the treatment, none of which have been demonstrated in a proper study, include a longer life, darker hair, better memory, better sleep, curing heart diseases, diabetes and Alzheimer's disease.[191][192][193][194][195] The approach is based on parabiosis studies such as those Irina Conboy has done on mice, but Conboy says young blood does not reverse aging (even in mice) and that those who offer those treatments have misunderstood her research.[192][193] Neuroscientist Tony Wyss-Coray, who also studied blood exchanges on mice as recently as 2014, said people offering those treatments are "basically abusing people's trust"[196][193] and that young blood treatments are "the scientific equivalent of fake news".[197] The treatment appeared in HBO's Silicon Valley fiction series.[196]

Two clinics in California, run by Jesse Karmazin and David C. Wright,[191] offer $8,000 injections of plasma extracted from the blood of young people. Karmazin has not published in any peer-reviewed journal and his current study does not use a control group.[197][196][191][193]

Microbiome alterations edit

Fecal microbiota transplantation[198][199] and probiotics are being investigated as means for life and healthspan extension.[200][201][202]

See also edit

Main articles: List of life extension topics and Index of life extension-related articles

References edit

  1. ^ Turner BS (2009). Can We Live Forever? A Sociological and Moral Inquiry. Anthem Press. p. 3.
  2. ^ "agerasia". Oxford English Dictionary (Online ed.). Oxford University Press. (Subscription or participating institution membership required.)
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Further reading edit

  • Bostrum N. "The Fable of the Dragon Tyrant".
  • de Grey A (3 December 2004). "We will be able to live to 1,000". BBC News.
  • Easterbrook G (October 2014). "What Happens When We All Live to 100?". The Atlantic. pp. 60–72.
  • Emanuel EJ (October 2014). "Why I Hope to Die at 75". The Atlantic. pp. 74–81.

External links edit

  • Life extension on Wikiversity

February 15, 2024
life, extension, other, uses, disambiguation, concept, extending, human, lifespan, either, modestly, through, improvements, medicine, dramatically, increasing, maximum, lifespan, beyond, generally, settled, limit, years, several, researchers, area, along, with. For other uses see Life extension disambiguation 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 limit of 125 years 1 Several researchers in the area along with life extensionists immortalists or longevists those who wish to achieve longer lives themselves postulate that future breakthroughs in tissue rejuvenation stem cells regenerative medicine molecular repair gene therapy pharmaceuticals and organ replacement such as with artificial organs or xenotransplantations will eventually enable humans to have indefinite lifespans through complete rejuvenation to a healthy youthful condition agerasia 2 The ethical ramifications if life extension becomes a possibility are debated by bioethicists The sale of purported anti aging products such as supplements and hormone replacement 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 3 The use of such hormone products has not been proven to be effective or safe 3 4 5 6 Contents 1 Average life expectancy and lifespan 2 Beliefs and methods 2 1 Senolytics and prolongevity drugs 2 2 Diets and supplements 2 2 1 Vitamins and antioxidants 2 2 1 1 Complications 2 2 2 Dietary restriction 2 2 3 Healthy diet 2 2 3 1 Optimal diet 2 3 Other approaches 2 3 1 Within the field 2 4 Hormone treatment 2 5 Lifestyle factors 2 6 Societal strategies 2 7 Low ambient temperature 3 History 3 1 Scientific research 4 Ethics and politics 4 1 Scientific controversy 4 2 Consumer motivations 4 3 Political parties 4 4 Silicon Valley 4 5 Commentators 4 6 Overpopulation concerns 4 7 Opinion polls 5 Aging as a disease 6 Research 6 1 Anti aging drugs 6 2 Nanotechnology 6 3 Cloning and body part replacement 6 4 Cyborgs 6 5 Cryonics 6 6 Strategies for engineered negligible senescence 6 7 Genetic editing 6 8 Fooling genes 6 9 Mind uploading 6 10 Young blood injection 6 11 Microbiome alterations 7 See also 8 References 9 Further reading 10 External linksAverage life expectancy and lifespan editMain article Senescence 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 7 Oxidation damage to cellular contents caused by free radicals is believed to contribute to aging as well 8 9 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 10 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 11 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 12 Another technique uses evolutionary pressures such as breeding from only older members or altering levels of extrinsic mortality 13 14 Some animals such as hydra planarian flatworms and certain sponges corals and jellyfish do not die of old age and exhibit potential immortality 15 16 17 18 Beliefs and methods editSee also Ageing Prevention and delay and Brain aging Senolytics and prolongevity drugs edit See also Geroprotector and MTOR inhibitors Rapamycin and rapalogs This section is an excerpt from Senolytic edit A senolytic from the words senescence and lytic destroying 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 19 A goal of this research is to discover or develop agents to delay prevent alleviate or reverse age related diseases 20 21 A related concept is senostatic which means to suppress senescence 22 Senolytics eliminate senescent cells whereas senomorphics with candidates such as Apigenin Everolimus and Rapamycin modulate properties of senescent cells without eliminating them suppressing phenotypes of senescence including the SASP 23 24 Senomorphic effects may be one major effect mechanism of a range of prolongevity drug candidates Such candidates are however typically not studied for just one mechanism but multiple There are biological databases of prolongevity drug candidates under research as well as of potential gene protein targets These are enhanced by longitudinal cohort studies electronic health records computational drug screening methods computational biomarker discovery methods and computational biodata interpretation personalized medicine methods 25 26 27 Besides rapamycin and senolytics the drug repurposing candidates studied most extensively include metformin acarbose spermidine and NAD enhancers 28 Many prolongevity drugs are synthetic alternatives or potential complements to existing nutraceuticals such as various sirtuin activating compounds under investigation like SRT2104 29 In some cases pharmaceutical administration is combined with that of neutraceuticals such as in the case of glycine combined with NAC 30 Often studies are structured based on or thematize specific prolongevity targets listing both nutraceuticals and pharmaceuticals together or separately such as FOXO3 activators 31 Researchers are also exploring ways to mitigate side effects from such substances possibly most notably rapamycin and its derivatives such as via protocols of intermittent administration 32 24 23 33 34 and have called for research that helps determine optimal treatment schedules including timing in general 35 Diets and supplements edit Vitamins and antioxidants edit See also Inflammaging and DNA damage theory of aging The free radical theory of aging suggests that antioxidant supplements might extend human life Reviews however have found that use of vitamin A as b carotene and vitamin E supplements possibly can increase mortality 36 37 Other reviews have found no relationship between vitamin E and other vitamins with mortality 38 Vitamin D supplementation of various dosages is investigated in trials 39 and there also is research into GlyNAC see above 30 Complications edit Complications of antioxidant supplementation especially continuous high dosages far above the RDA include that reactive oxygen species ROS which are mitigated by antioxidants have been found to be physiologically vital for signal transduction gene regulation and redox regulation among others implying that their complete elimination would be harmful In particular one way of multiple they can be detrimental is by inhibiting adaptation to exercise such as muscle hypertrophy e g during dedicated periods of caloric surplus 40 41 42 There is also research into stimulating activating fueling endogenous antioxidant generation in particular e g of neutraceutical glycine and pharmaceutical NAC 43 Antioxidants can change the oxidation status of different e g tissues targets or sites each with potentially different implications especially for different concentrations 44 45 46 47 A review suggests mitochondria have a hormetic response to ROS whereby low oxidative damage can be beneficial 48 Dietary restriction edit Main article Diet and longevity See also Caloric restriction mimetic As of 2021 there is no clinical evidence that any dietary restriction practice contributes to human longevity 49 Healthy diet edit Research suggests that increasing adherence to Mediterranean diet patterns is associated with a reduction in total and cause specific mortality extending health and lifespan 50 51 52 53 Research is identifying the key beneficial components of the Mediterranean diet 54 55 Studies suggest dietary changes are a factor of national relative rises in life span 56 Optimal diet edit See also Sustainable consumption Sustainable food consumption Approaches to develop optimal diets for health and lifespan or longevity diets 57 include modifying the Mediterranean diet as the baseline via nutrition science For instance via additional increase in plant based 58 57 foods alongside additional restriction of meat intake 59 meat reduction is or can be typically healthy 60 keeping alcohol consumption of any type at a minimum conventional Mediterranean diets include alcohol consumption i e of wine which is under research due to data suggesting negative long term brain impacts even at low moderate consumption levels 61 62 fully replacing refined grains some guidelines of Mediterranean diets do not clarify or include the principle of whole grain consumption instead of refined grains Whole grains are included in Mediterranean diets 63 64 Other approaches edit Further advanced biosciences based approaches include Genetic and epigenetic alterations Human genetic enhancement for pro longevity and protective genes see genetics of aging 65 26 Cellular reprogramming in vivo reprogramming to complement or augment human regenerative capacity and rejuvenate or replace cells 66 67 26 Epigenetic reprogramming early stage research about rejuvenating repairing epigenetic machinery 68 Stem cell interventions Increasing the number and quality of stem cells and activate regenerative signals 69 70 Nanomedicine early stage research of in vivo pro longevity nanotechnology 71 72 Tissue engineering of tissues and organs 73 see also xenotransplantation and artificial organ Endogenous circulating biomolecules Blood proteins of blood from young animals have shown some pro longevity potential in animal studies e g via transfer of blood or plasma and of plasma proteins 27 Moreover exerkines signalling biomolecules released during after exercise have also shown promising results 74 Exerkines include myokines Extracellular vesicles were shown to be secreted concomitantly with exerkines and are also investigated 75 76 See also body fluid and cerebrospinal fluid Personalized interventions future studies may tailor and investigate personalized medicine type interventions 77 For instance effects of interventions or e g dosages may vary per age 57 and or genome A review suggests that the field of precision medicine and geroscience will have to interact closely 77 see also combination therapy Peptides such as MOTS c released by mitochondria 78 Mitochondria modulation early stage research indicates mitochondrial interventions such as mitochondrial transplantation may have potential to be efficacious 79 26 80 81 82 See also mitochondrial theory of ageing Within the field edit See also Biogerontology There is a need and research into the development of aging biomarkers such as the epigenetic clock to assess the ageing process and the efficacy of interventions to bypass the need for large scale longitudinal studies 77 26 Such biomarkers may also include in vivo brain imaging 83 Reviews sometimes include structured tables that provide systematic overviews of intervention drug candidates with a review calling for integrating current knowledge with multi omics health records and drug safety data to predict drugs that can improve health in late life and listing major outstanding questions 25 Biological databases of prolongevity drug candidates under research as well as of potential gene protein targets include GenAge DrugAge and Geroprotectors 25 84 A review has pointed out that the approach of epidemiological comparison of how a low versus a high consumption of an isolated macronutrient and its association with health and mortality may not only fail to identify protective or detrimental nutrition patterns but may lead to misleading interpretations It proposes a multi pillar approach and summarizes findings towards constructing multi system considering and at least age personalized dynamic refined longevity diets Epidemiological type observational studies included in meta analyses should according to the study at least be complemented by 1 basic research focused on lifespan and healthspan 2 carefully controlled clinical trials and 3 studies of individuals and populations with record longevity 57 Hormone treatment edit The anti aging industry offers several hormone therapies Some of these have been criticized for possible dangers and a lack of proven effect For example the American Medical Association has been critical of some anti aging hormone therapies 3 While growth hormone GH decreases with age the evidence for use of growth hormone as an anti aging therapy is mixed and based mostly on animal studies There are mixed reports that GH or IGF 1 modulates the aging process in humans and about whether the direction of its effect is positive or negative 85 Klotho 69 86 and exerkines 74 see above like irisin 87 are being investigated for potential pro longevity therapies Lifestyle factors edit See also Lifestyle disease Loneliness isolation social life and support 53 88 exercise physical activity partly via neurobiological effects and increased NAD levels 53 89 77 78 90 91 psychological characteristics personality possibly highly indirectly 92 93 sleep duration 53 circadian rhythms patterns of sleep drug administration and feeding 94 95 96 type of leisure activities 53 not smoking 53 altruistic emotions and behaviors 97 98 subjective well being 99 mood 53 and stress including via heat shock protein 53 100 are investigated as potential modulatable factors of life extension Healthy lifestyle practices and healthy diet have been suggested as first line function preserving strategies with pharmacological agents including existing and new pharmaceuticals and novel nutraceutical compounds serving as potential complementary approaches 101 Societal strategies edit See also Ethics and politics Scientific research Clinical trial Metascience Telehealth Health economics Health education and Medical research nbsp Life expectancy vs healthcare spending of rich OECD countries US average of 10 447 in 2018 102 Collectively addressing common causes of death could extend lifespans of populations and humanity overall For instance a 2020 study indicates that the global mean loss of life expectancy LLE from air pollution in 2015 was 2 9 years substantially more than for example 0 3 years from all forms of direct violence albeit a significant fraction of the LLE a measure similar to years of potential life lost is considered to be unavoidable 103 Regular screening and doctor visits has been suggested as a lifestyle societal intervention 53 See also medical test and biomarker Health policy and changes to standard healthcare could support the adoption of the field s conclusions a review suggests that the longevity diet would be a valuable complement to standard healthcare and that taken as a preventative measure it could aid in avoiding morbidity sustaining health into advanced age as a form of preventive healthcare 57 It has been suggested that in terms of healthy diets Mediterranean style diets could be promoted by countries for ensuring healthy by default choices to ensure the healthiest choice is the easiest choice and with highly effective measures including dietary education food checklists and recipes that are simple palatable and affordable 104 A review suggests that targeting the aging process per se may be a far more effective approach to prevent or delay aging associated pathologies than treatments specifically targeted to particular clinical conditions 105 Low ambient temperature edit Low ambient temperature as a physical factor affecting free radical levels was identified as a treatment producing exceptional lifespan increase in Drosophila melanogaster and other living beings 106 History editFurther information Timeline of senescence research 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 Rene 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 siecle end of the century 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 or life extensionism Among the foremost researchers of life extension at this period were the Nobel Prize winning biologist Elie Metchnikoff 1845 1916 the author of the cell theory of immunity and vice director of Institut Pasteur in Paris and Charles Edouard Brown Sequard 1817 1894 the president of the French Biological Society and one of the founders of modern endocrinology 107 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 1561 1626 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 1627 1691 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 1873 1944 was inspired by a belief in indefinite human lifespan that he developed after experimenting with cells says Hughes 108 Regulatory and legal struggles between the Food and Drug Administration FDA and the Life Extension organization included seizure of merchandise and court action 109 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 110 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 111 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 112 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 113 transhumanist philosopher Zoltan Istvan who proposes that the transhumanist must safeguard one s own existence above all else 114 futurist George Dvorsky who considers aging to be a problem that desperately needs to be solved 115 and recording artist Steve Aoki who has been called one of the most prolific campaigners for life extension 116 Scientific research edit See also Timeline of senescence research In 1991 the American Academy of Anti Aging Medicine A4M was formed The American Board of Medical Specialties recognizes neither anti aging medicine nor the A4M s professional standing 117 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 118 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 119 It is led by Arthur D Levinson 120 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 121 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 122 123 124 125 Ethics and politics editScientific controversy edit Some critics dispute the portrayal of aging as a disease For example Leonard Hayflick who determined that fibroblasts are limited to around 50 cell divisions reasons that aging is an unavoidable consequence of entropy Hayflick and fellow biogerontologists Jay Olshansky and Bruce Carnes have strongly criticized the anti aging industry in response to what they see as unscrupulous profiteering from the sale of unproven anti aging supplements 5 Consumer motivations edit Research by Sobh and Martin 2011 suggests that people buy anti aging products to obtain a hoped for self e g keeping a youthful skin or to avoid a feared self e g looking old The research shows that when consumers pursue a hoped for self it is expectations of success that most strongly drive their motivation to use the product The research also shows why doing badly when trying to avoid a feared self is more motivating than doing well When product use is seen to fail it is more motivating than success when consumers seek to avoid a feared self 126 Political parties edit Though many scientists state 127 that life extension and radical life extension are possible there are still no international or national programs focused on radical life extension There are political forces working both for and against life extension By 2012 in Russia the United States Israel and the Netherlands the Longevity political parties started They aimed to provide political support to radical life extension research and technologies and ensure the fastest possible and at the same time soft transition of society to the next step life without aging and with radical life extension and to provide access to such technologies to most currently living people 128 Silicon Valley edit Some tech innovators and Silicon Valley entrepreneurs have invested heavily into anti aging research This includes Jeff Bezos founder of Amazon Larry Ellison founder of Oracle Peter Thiel former PayPal CEO 129 Larry Page co founder of Google Peter Diamandis 130 Sam Altman CEO of OpenAI invested in Retro Biosciences and Brian Armstrong founder of Coinbase and NewLimit 131 Commentators edit Leon Kass chairman of the US President s Council on Bioethics from 2001 to 2005 has questioned whether potential exacerbation of overpopulation problems would make life extension unethical 132 He states his opposition to life extension with the words simply to covet a prolonged life span for ourselves is both a sign and a cause of our failure to open ourselves to procreation and to any higher purpose The desire to prolong youthfulness is not only a childish desire to eat one s life and keep it it is also an expression of a childish and narcissistic wish incompatible with devotion to posterity 133 John Harris former editor in chief of the Journal of Medical Ethics argues that as long as life is worth living according to the person himself we have a powerful moral imperative to save the life and thus to develop and offer life extension therapies to those who want them 134 Transhumanist philosopher Nick Bostrom has argued that any technological advances in life extension must be equitably distributed and not restricted to a privileged few 135 In an extended metaphor entitled The Fable of the Dragon Tyrant Bostrom envisions death as a monstrous dragon who demands human sacrifices In the fable after a lengthy debate between those who believe the dragon is a fact of life and those who believe the dragon can and should be destroyed the dragon is finally killed Bostrom argues that political inaction allowed many preventable human deaths to occur 136 Overpopulation concerns edit Controversy about life extension is due to fear of overpopulation and possible effects on society 137 Biogerontologist Aubrey De Grey counters the overpopulation critique by pointing out that the therapy could postpone or eliminate menopause allowing women to space out their pregnancies over more years and thus decreasing the yearly population growth rate 138 Moreover the philosopher and futurist Max More argues that given the fact the worldwide population growth rate is slowing down and is projected to eventually stabilize and begin falling superlongevity would be unlikely to contribute to overpopulation 137 Opinion polls edit A Spring 2013 Pew Research poll in the United States found that 38 of Americans would want life extension treatments and 56 would reject it However it also found that 68 believed most people would want it and that only 4 consider an ideal lifespan to be more than 120 years The median ideal lifespan was 91 years of age and the majority of the public 63 viewed medical advances aimed at prolonging life as generally good 41 of Americans believed that radical life extension RLE would be good for society while 51 said they believed it would be bad for society 139 One possibility for why 56 of Americans claim they would reject life extension treatments may be due to the cultural perception that living longer would result in a longer period of decrepitude and that the elderly in our current society are unhealthy 140 Religious people are no more likely to oppose life extension than the unaffiliated 139 though some variation exists between religious denominations Aging as a disease editMost mainstream medical organizations and practitioners do not consider aging to be a disease Biologist David Sinclair says I don t see aging as a disease but as a collection of quite predictable diseases caused by the deterioration of the body 141 The two main arguments used are that aging is both inevitable and universal while diseases are not 142 However not everyone agrees Harry R Moody director of academic affairs for AARP notes that what is normal and what is disease strongly depend on a historical context 143 David Gems assistant director of the Institute of Healthy Ageing argues that aging should be viewed as a disease 144 In response to the universality of aging David Gems notes that it is as misleading as arguing that Basenji are not dogs because they do not bark 145 Because of the universality of aging he calls it a special sort of disease Robert M Perlman coined the terms aging syndrome and disease complex in 1954 to describe aging 146 The discussion whether aging should be viewed as a disease or not has important implications One view is this would stimulate pharmaceutical companies to develop life extension therapies and in the United States of America it would also increase the regulation of the anti aging market by the Food and Drug Administration FDA Anti aging now falls under the regulations for cosmetic medicine which are less tight than those for drugs 145 147 Research editTheoretically 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 148 149 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 150 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 150 Anti aging drugs edit There are a number of chemicals intended to slow the aging process currently being studied in animal models 151 One type of research is related to the observed effects of a calorie restriction CR diet which has been shown to extend lifespan in some animals 152 Based on that research there have been attempts to develop drugs that will have the same effect on the aging process as a caloric restriction diet which are known as caloric restriction mimetic drugs Some drugs that are already approved for other uses have been studied for possible longevity effects on laboratory animals because of a possible CR mimic effect they include rapamycin for mTOR inhibition 153 and metformin for AMPK activation 154 Sirtuin activating polyphenols such as resveratrol and pterostilbene 155 156 157 and flavonoids such as quercetin and fisetin 158 as well as oleic acid 159 are dietary supplements that have also been studied in this context Other popular supplements with less clear biological pathways to target aging include lipoic acid 160 senolytics such as curcumin 158 and Coenzyme Q10 161 Daily low doses of ethanol as a potential supplement in spite of its highly negative hormesis response at higher doses has also been studied 162 Other attempts to create anti aging drugs have taken different research paths One notable direction of research explores the possibility of lengthening chromosomal telomeres protective caps at the end of chromosomes by reactivating telomerase the enzyme responsible for telomere length maintenance However telomerase is virtually unexpressed in normal healthy somatic cells 163 and there are potential dangers in this approach as research has shown a strong link between telomerase expression and cancer and tumors in somatic non germ line cells 164 165 Nanotechnology edit Future advances in nanomedicine could give rise to life extension through the repair of many processes thought to be responsible for aging K Eric Drexler one of the founders of nanotechnology postulated cell repair machines including ones operating within cells and utilizing as yet hypothetical molecular computers in his 1986 book Engines of Creation Raymond Kurzweil a futurist and transhumanist stated in his book The Singularity Is Near that he believes that advanced medical nanorobotics could completely remedy the effects of aging by 2030 166 According to Richard Feynman it was his former graduate student and collaborator Albert Hibbs who originally suggested to him circa 1959 the idea of a medical use for Feynman s theoretical nanomachines see biological machine Hibbs suggested that certain repair machines might one day be reduced in size to the point that it would in theory be possible to as Feynman put it swallow the doctor The idea was incorporated into Feynman s 1959 essay There s Plenty of Room at the Bottom 167 Cloning and body part replacement edit Some life extensionists suggest that therapeutic cloning and stem cell research could one day provide a way to generate cells body parts or even entire bodies generally referred to as reproductive cloning that would be genetically identical to a prospective patient Recently the US Department of Defense initiated a program to research the possibility of growing human body parts on mice 168 Complex biological structures such as mammalian joints and limbs have not yet been replicated Dog and primate brain transplantation experiments were conducted in the mid 20th century but failed due to rejection and the inability to restore nerve connections As of 2006 the implantation of bio engineered bladders grown from patients own cells has proven to be a viable treatment for bladder disease 169 Proponents of body part replacement and cloning contend that the required biotechnologies are likely to appear earlier than other life extension technologies The use of human stem cells particularly embryonic stem cells is controversial Opponents objections generally are based on interpretations of religious teachings or ethical considerations 170 Proponents of stem cell research point out that cells are routinely formed and destroyed in a variety of contexts Use of stem cells taken from the umbilical cord or parts of the adult body may not provoke controversy 171 The controversies over cloning are similar except general public opinion in most countries stands in opposition to reproductive cloning Some proponents of therapeutic cloning predict the production of whole bodies lacking consciousness for eventual brain transplantation Cyborgs edit Main article Cyborg Replacement of biological susceptible to diseases organs with mechanical ones could extend life This is the goal of the 2045 Initiative 172 Cryonics edit Main article Cryonics Cryonics is the low temperature freezing usually at 196 C or 320 8 F or 77 1 K of a human corpse with the hope that resuscitation may be possible in the future 173 174 It is regarded with skepticism within the mainstream scientific community and has been characterized as quackery 175 Strategies for engineered negligible senescence edit Main articles Strategies for engineered negligible senescence and Genetics of aging Another proposed life extension technology aims to combine existing and predicted future biochemical and genetic techniques SENS proposes that rejuvenation may be obtained by removing aging damage via the use of stem cells and tissue engineering telomere lengthening machinery allotopic expression of mitochondrial proteins targeted ablation of cells immunotherapeutic clearance and novel lysosomal hydrolases 176 While some biogerontologists find these ideas worthy of discussion 177 178 others contend that the alleged benefits are too speculative given the current state of technology referring to it as fantasy rather than science 4 6 Genetic editing edit Main articles Genetics of aging and Genome editing Genome editing in which nucleic acid polymers are delivered as a drug and are either expressed as proteins interfere with the expression of proteins or correct genetic mutations has been proposed as a future strategy to prevent aging 179 180 A large array of genetic modifications have been found to increase lifespan in model organisms such as yeast nematode worms fruit flies and mice As of 2013 the longest extension of life caused by a single gene manipulation was roughly 50 in mice and 10 fold in nematode worms 181 nbsp Healthspan parental lifespan and longevity are highly genetically correlated 182 In July 2020 scientists using public biological data on 1 75 m people with known lifespans overall identify 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 and identify haem metabolism as a promising candidate for further research within the field Their study suggests that high levels of iron in the blood likely reduce and genes involved in metabolising iron likely increase healthy years of life in humans 183 182 The same month other 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 184 185 Fooling genes edit In The Selfish Gene Richard Dawkins describes an approach to life extension that involves fooling genes into thinking the body is young 186 Dawkins attributes inspiration for this idea to Peter Medawar The basic idea is that our bodies are composed of genes that activate throughout our lifetimes some when we are young and others when we are older Presumably these genes are activated by environmental factors and the changes caused by these genes activating can be lethal It is a statistical certainty that we possess more lethal genes that activate in later life than in early life Therefore to extend life we should be able to prevent these genes from switching on and we should be able to do so by identifying changes in the internal chemical environment of a body that take place during aging and by simulating the superficial chemical properties of a young body 187 Mind uploading edit Main article Mind uploading One hypothetical future strategy that as some suggest who eliminates the complications related to a physical body involves the copying or transferring e g by progressively replacing neurons with transistors of a conscious mind from a biological brain to a non biological computer system or computational device The basic idea is to scan the structure of a particular brain in detail and then construct a software model of it that is so faithful to the original that when run on appropriate hardware it will behave in essentially the same way as the original brain 188 Whether or not an exact copy of one s mind constitutes actual life extension is matter of debate However critics argue that the uploaded mind would simply be a clone and not a true continuation of a person s consciousness 189 Some scientists believe that the dead may one day be resurrected through simulation technology 190 Young blood injection edit Further information Young blood transfusion Some clinics currently offer injection of blood products from young donors The alleged benefits of the treatment none of which have been demonstrated in a proper study include a longer life darker hair better memory better sleep curing heart diseases diabetes and Alzheimer s disease 191 192 193 194 195 The approach is based on parabiosis studies such as those Irina Conboy has done on mice but Conboy says young blood does not reverse aging even in mice and that those who offer those treatments have misunderstood her research 192 193 Neuroscientist Tony Wyss Coray who also studied blood exchanges on mice as recently as 2014 said people offering those treatments are basically abusing people s trust 196 193 and that young blood treatments are the scientific equivalent of fake news 197 The treatment appeared in HBO s Silicon Valley fiction series 196 Two clinics in California run by Jesse Karmazin and David C Wright 191 offer 8 000 injections of plasma extracted from the blood of young people Karmazin has not published in any peer reviewed journal and his current study does not use a control group 197 196 191 193 Microbiome alterations edit Fecal microbiota transplantation 198 199 and probiotics are being investigated as means for life and healthspan extension 200 201 202 See also editMain articles List of life extension topics and Index of life extension related articles Advanced glycation end product Aging brain Aging movement control Alzheimer s disease Anti aging movement Biological immortality Centenarian Clinical Interventions in Aging Dementia DNA damage theory of aging Human enhancement Immortal DNA strand hypothesis Immortality Maximum lifespan Particulates Rejuvenation Research Senescence Slow aging Supercentenarian Timeline of senescence research Toxic substances Transgenerational design TranshumanismReferences edit Turner BS 2009 Can We Live Forever A 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Multivariate genomic scan implicates novel loci and haem metabolism in human ageing Nature Communications 11 1 3570 Bibcode 2020NatCo 11 3570T doi 10 1038 s41467 020 17312 3 PMC 7366647 PMID 32678081 nbsp Text and images are available under a Creative Commons Attribution 4 0 International License University of Edinburgh 16 July 2020 Blood iron levels could be key to slowing ageing gene study shows Phys org Retrieved 18 August 2020 University of California 16 July 2020 Researchers discover 2 paths of aging and new insights on promoting healthspan Phys org Retrieved 17 August 2020 Li Y Jiang Y Paxman J O Laughlin R Klepin S Zhu Y et al July 2020 A programmable fate decision landscape underlies single cell aging in yeast Science 369 6501 325 329 Bibcode 2020Sci 369 325L doi 10 1126 science aax9552 PMC 7437498 PMID 32675375 Dawkins R 2006 1976 The Selfish Gene New York Oxford University Press pp 41 42 ISBN 978 0 19 929115 1 Dawkins R 2006 1976 The Selfish Gene New York Oxford University Press p 42 ISBN 978 0 19 929115 1 Sandberg A Bostrom N 2008 Whole Brain Emulation A Roadmap PDF Technical Report 2008 3 Future of Humanity Institute Oxford University Retrieved 7 March 2013 The basic idea is to take a particular brain scan its structure in detail and construct a software model of it that is so faithful to the original that when run on appropriate hardware it will behave in essentially the same way as the original brain Graziano M 13 September 2019 Will Your Uploaded Mind Still Be You Wall Street Journal Retrieved 19 May 2020 Bostrom N 19 January 2010 Are You Living in a Computer Simulation a b c Maxmen A 13 January 2017 Questionable Young Blood Transfusions Offered in U S as Anti Aging Remedy MIT Technology Review Retrieved 5 November 2017 a b Kirkey S 2 November 2017 This anti aging startup says US 8 000 worth of young blood can help you live longer National Post Retrieved 5 November 2017 a b c d Osborne S 20 August 2017 Teenagers blood being sold for 6 200 a shot The Independent Archived from the original on 14 June 2022 Haynes G 21 August 2017 Ambrosia the startup harvesting the blood of the young The Guardian Retrieved 5 November 2017 Farr C 31 May 2017 This start up is offering 8 000 blood transfusions from teens to people who want to fight aging CNBC Retrieved 5 November 2017 a b c Kosoff M 1 June 2017 This anti aging start up is charging thousands of dollars for teen blood Vanity Fair Retrieved 5 November 2017 a b Foley KE 1 June 2017 A startup that charges 8 000 for young blood transfusions swears they re worth every penny Quartz Retrieved 5 November 2017 Haridy R 10 August 2021 Gut bacteria from young mice reverse signs of brain aging in old mice New Atlas Retrieved 21 September 2021 Boehme M Guzzetta KE Bastiaanssen TF Van De Wouw M Moloney GM Gual Grau A et al August 2021 Microbiota from young mice counteracts selective age associated behavioral deficits Nature Aging 1 8 666 676 doi 10 1038 s43587 021 00093 9 ISSN 2662 8465 PMID 37117767 Sharma D Kober MM Bowe WP January 2016 Anti Aging Effects of Probiotics Journal of Drugs in Dermatology 15 1 9 12 PMID 26741377 Ayala FR Bauman C Cogliati S Lenini C Bartolini M Grau R March 2017 Microbial flora probiotics Bacillus subtilis and the search for a long and healthy human longevity Microbial Cell 4 4 133 136 doi 10 15698 mic2017 04 569 PMC 5376353 PMID 28435840 Tsai YC Cheng LH Liu YW Jeng OJ Lee YK 2021 Gerobiotics probiotics targeting fundamental aging processes Bioscience of Microbiota Food and Health 40 1 1 11 doi 10 12938 bmfh 2020 026 PMC 7817508 PMID 33520563 Further reading editBostrum N The Fable of the Dragon Tyrant de Grey A 3 December 2004 We will be able to live to 1 000 BBC News Easterbrook G October 2014 What Happens When We All Live to 100 The Atlantic pp 60 72 Emanuel EJ October 2014 Why I Hope to Die at 75 The Atlantic pp 74 81 External links editLife extension on Wikiversity Retrieved from https en wikipedia org w index php title Life extension amp oldid 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