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Life extension

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]

Senolytics and prolongevity drugs[edit]

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]

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

As of 2021, there is no clinical evidence that any dietary 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] It shares various characteristics with the similarly beneficial Okinawa diet.[56] Potential anti-aging mechanisms of various nutrients are not yet understood.[57] Shares of macronutrients[58][59] and level of caloric intake may also be of significance, including in periods when no dietary restriction occurs[58] – such as not having a fat-intake that is too low[59] and not having a prolonged caloric surplus or caloric deficit that is too large.

Studies suggest dietary changes are a major cause of national relative rises in life-span.[60]

Microbiome[edit]

Mechanistically, research suggests that the gut microbiome, which varies per person and changes throughout lifespan, is also involved in the beneficial effects, due to which various diet supplementations with prebiotics, various diverse (multi-strain) probiotics and synbiotics, and fecal microbiota transplantation are being investigated for life extension,[61][27][62] mainly for prolonging healthspan,[63][64][65] with many important questions being unresolved.[66]


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