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. 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 (agerasia) through complete rejuvenation to a healthy youthful condition. 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. The use of such hormone products has not been proven to be effective or safe.
Average life expectancy and lifespan
During the process of aging, an organism accumulates damage to its macromolecules, cells, tissues, and organs. Specifically, aging is characterized as and thought to be caused by "genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, and altered intercellular communication." Oxidation damage to cellular contents caused by free radicals is believed to contribute to aging as well.
The longest documented human lifespan is 122 years 164 days, the case of Jeanne Calment who according to records was born in 1875 and died in 1997, whereas the maximum lifespan of a wildtype mouse, commonly used as a model in research on aging, is about three years. Genetic differences between humans and mice that may account for these different aging rates include differences in efficiency of DNA repair, antioxidant defenses, energy metabolism, proteostasis maintenance, and recycling mechanisms such as autophagy.
The average life expectancy in a population is lowered by infant and child mortality, which are frequently linked to infectious diseases or nutrition problems. Later in life, vulnerability to accidents and age-related chronic disease such as cancer or cardiovascular disease play an increasing role in mortality. Extension of life expectancy and lifespan can often be achieved by access to improved medical care, vaccinations, good diet, exercise, and avoidance of hazards such as smoking.
Maximum lifespan is determined by the rate of aging for a species inherent in its genes and by environmental factors. Widely recognized methods of extending maximum lifespan in model organisms such as nematodes, fruit flies, and mice include caloric restriction, gene manipulation, and administration of pharmaceuticals. Another technique uses evolutionary pressures such as breeding from only older members or altering levels of extrinsic mortality. Some animals such as hydra, planarian flatworms, and certain sponges, corals, and jellyfish do not die of old age and exhibit potential immortality.
Beliefs and methods
Senolytics and prolongevity drugs
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. 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.
Recently, artificial intelligence has been used to discover new senolytics, resulting in the identification of structurally distinct senolytic compounds with more favorable medicinal chemistry properties than previous senolytic candidates.
Such strategies as well as testing with model organisms and xenografts may attempt to or help address difficulties of trials with humans which have relatively long lifespans (compared to other animals) as well as the (larger) need to protect human health from early-trial-stage interventions (in clinical trials).
Many prolongevity drugs are synthetic alternatives or potential complements to existing nutraceuticals, such as various sirtuin-activating compounds under investigation like SRT2104. In some cases pharmaceutical administration is combined with that of neutraceuticals – such as in the case of glycine combined with NAC. Often studies are structured based on or thematize specific prolongevity targets, listing both nutraceuticals and pharmaceuticals (together or separately) such as FOXO3-activators.
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 and have called for research that helps determine optimal treatment schedules (including timing) in general.
Diets and supplements
Vitamins and antioxidants
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. Other reviews have found no relationship between vitamin E and other vitamins with mortality. Vitamin D supplementation of various dosages is investigated in trials and there also is research into GlyNAC .
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). There is also research into stimulating/activating/fueling endogenous antioxidant generation, in particular e.g. of neutraceutical glycine and pharmaceutical NAC. Antioxidants can change the oxidation status of different e.g. tissues, targets or sites each with potentially different implications, especially for different concentrations. A review suggests mitochondria have a hormetic response to ROS, whereby low oxidative damage can be beneficial.
Research suggests that increasing adherence to Mediterranean diet patterns is associated with a reduction in total and cause-specific mortality, extending health- and lifespan. Research is identifying the key beneficial components of the Mediterranean diet. It shares various characteristics with the similarly beneficial Okinawa diet. Potential anti-aging mechanisms of various nutrients are not yet understood. Shares of macronutrients and level of caloric intake may also be of significance, including in periods when no dietary restriction occurs – such as not having a fat-intake that is too low and not having a prolonged caloric surplus or caloric deficit that is too large.
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, mainly for prolonging healthspan, with many important questions being unresolved.
Approaches to develop optimal diets for health- and lifespan (or "longevity diets") include:
- modifying or further particularizing the Mediterranean diet as the baseline via nutrition science. For instance, via:
- (additional) increase in plant-based (but protein-rich) foods alongside additional restriction of meat intake – meat reduction is (or can be) typically healthy,
- regular moderate consumption of green tea or (filtered) coffee while ensuring adequate calcium intake
- (additional) increase in omega-3-containing seafoods (see also: algal oil)
- adding various foods thought to be healthy (e.g. due to results about various mechanistic effects) to the regular dietary consumption patterns (see also: functional food)
- increasing the intake of high-spermidine foods – studies suggest spermidine could extend lifespan, with high amounts that are larger than common supplements being present in fungi (e.g. mushrooms) and green peas
- increasing resistant starch-intake – legumes, especially e.g. green peas contain large amounts of resistant starch, especially if pre-cooked as cooling the cooked peas in a refrigerator substantially increases the resistant starch content due to starch retrogradation. It is a prebiotic (see Microbiome) and may promote healthy aging.
- 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. Anthocyanins which are present in red wine and suggested along with other flavanols to be a candidate for further longevity research are also present in comparable concentrations in bilberry and elderberry
- 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-grain are a significant source of spermidine and are associated with longevity. They are a main characteristic pillar of Mediterranean diets according to multiple reviews.
- aiming for a sufficient level of food variety and diversity – which some guidelines of Mediterranean diets do not clarify or include. One review suggests that food variety and diversity could be a factor of diet quality, and another review indicates that sufficient food variety may at least in some specific cases "increase intake of important nutrients and positively affect the gut microbiome structure and function". The required level of food variety may or may not be low and vary per person and diet.
- completely eliminating processed foods from the diet – some guidelines of Mediterranean diets may not clarify this principle. Diets associated with longevity are characterized by minimally processed foods.
- adjusting the diet for personal characteristics such as age as effects of e.g. macronutrient intake can vary per age 
- inferring an optimal diet indiscriminately for all levels and forms of physical activities and age and other person-characteristics by integrating the available meta-analyses and data from mostly observational studies.
- This has been done for a tool and visualizations that show populations' relative general life extension potentials of (shifting diets towards) different food groups, suggesting i.a. that a 20-years old male in Europe who switches to the "optimal diet" could gain a mean of ~13.7 years of life and a 60-years old female in the U.S. switching to the "optimal diet" could gain a mean of ~8.0 years of life. It found the largest gains would be made by eating more legumes, whole grains, and nuts, and less red meat and processed meat. The optimal diet contains no consumption of sugar-sweetened beverages (moving from "typical Western diet" of 500 g/day to 0 g/day). The study notes of uncertainty in "the effect of eggs, white meat, and oils, individual variation in protective and risk factors, uncertainties for future development of medical treatments; and changes in lifestyle".
Beyond, research into senolytics and (synthetic) prolongevity-drugs, vitamins and antioxidants, prebiotics and probiotics, there are neutraceuticals – dietary supplements and bioactive plant compounds (phytochemicals) but not pharmaceuticals – that are being investigated in life sciences, nutrition science and gerontology for potential health- and lifespan extension in healthy humans. Sometimes, their use is researched or recommended as a way to correct nutritional deficiencies from switching to otherwise healthy foods – in particular from replacing meat consumption with a higher intake of plant-based foods. Especially, but not only, in such cases the supplementation of minerals and various specific micronutrients is investigated. Correcting magnesium deficiency for instance could prolong life. Many supplements are researched primarily for potential improvements in health and healthspan rather than for extending lifespan.
Some studies hypothesize that relative health and longevity benefits of various foods and diets can be largely or to a large part attributed to the nutraceuticals they contain. Some studies suggest increasing the intake of specific foods based on such results, while some investigate supplementation, including of dosages that are impractical to achieve with whole foods.
Researched substances include various polyphenols such as pterostilbene or flavonoids, notably epicatechin. Some herbal-extracts like rhodiola rosea are also being investigated due to results of tests with model organisms. Some of these are AMPK activators and hence caloric restriction mimetics (some possibly exercise mimetics as well). AMPK activators include resveratrol and berberine. Many such nutraceuticals are also potent antioxidants. Like prolongevity-drugs and bioactive compounds in general, they can have multiple potential effect mechanisms, the polyphenol resveratrol for instance also activates possibly pro-longevity sirtuin activity.
A common issue with many already-existing natural nutraceuticals like resveratrol is their low bioavailability. Their side-effects are often low compared to several major longevity drug candidates. On the other hand, they are considered to often have "intrinsic natural bio-compatibility and safety". Some of the compounds can have a "biphasic dose response" (a trait/effect of hormesis) whereby they (can) have beneficial effects at low or moderate doses and toxic effects at high doses.
Further advanced biosciences-based approaches include:
- Genetic and epigenetic alterations: Human genetic enhancement for pro-longevity and protective genes – see genetics of aging
- Cellular reprogramming': in vivo reprogramming to complement or augment human regenerative capacity and rejuvenate or replace cells
- Epigenetic reprogramming: early-stage research about rejuvenating/repairing epigenetic machinery
- Stem-cell interventions: "Increasing the number and quality of stem cells and activate regenerative signals"
- Nanomedicine: early-stage research of in vivo pro-longevity nanotechnology
- Tissue engineering: of tissues and organs (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). Moreover, exerkines – signalling biomolecules released during/after exercise – have also shown promising results. Exerkines include myokines. Extracellular vesicles were shown to be secreted concomitantly with exerkines and are also investigated. (See also: body fluid and cerebrospinal fluid)
- Personalized interventions: future studies may tailor and investigate personalized medicine-type interventions For instance, effects of interventions or e.g. dosages may vary per age and/or genome. A review suggests that the field of precision medicine and geroscience will have to interact closely (see also: combination therapy)
- Peptides: such as MOTS-c released by mitochondria
- Mitochondria modulation: early-stage research indicates mitochondrial interventions such as mitochondrial transplantation may have potential to be efficacious (See also: mitochondrial theory of ageing)
Within the field
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". Such biomarkers may also include in vivo brain imaging.
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. Biological databases of prolongevity drug candidates under research as well as of potential gene/protein targets include GenAge, DrugAge and Geroprotectors.
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".
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.
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.
Loneliness/isolation, social life and support, exercise/physical activity (partly via neurobiological effects and increased NAD+ levels), psychological characteristics/personality (possibly highly indirectly), sleep duration, circadian rhythms (patterns of sleep, drug-administration and feeding), type of leisure activities, not smoking, altruistic emotions and behaviors, subjective well-being, mood and stress (including via heat shock protein) 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".
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.
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.
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".
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".
Low ambient temperature
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.
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.
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.
Regulatory and legal struggles between the Food and Drug Administration (FDA) and the Life Extension organization included seizure of merchandise and court action. In 1991, Saul Kent and Bill Faloon, the principals of the organization, were jailed for four hours and were released on $850,000 bond each. After 11 years of legal battles, Kent and Faloon convinced the US Attorney's Office to dismiss all criminal indictments brought against them by the FDA.
In 2003, Doubleday published "The Immortal Cell: One Scientist's Quest to Solve the Mystery of Human Aging," by Michael D. West. West emphasised the potential role of embryonic stem cells in life extension.
Other modern life extensionists include writer Gennady Stolyarov, who insists that death is "the enemy of us all, to be fought with medicine, science, and technology"; transhumanist philosopher Zoltan Istvan, who proposes that the "transhumanist must safeguard one's own existence above all else"; futurist George Dvorsky, who considers aging to be a problem that desperately needs to be solved; and recording artist Steve Aoki, who has been called "one of the most prolific campaigners for life extension".
In 2003, Aubrey de Grey and David Gobel formed the Methuselah Foundation, which gives financial grants to anti-aging research projects. In 2009, de Grey and several others founded the SENS Research Foundation, a California-based scientific research organization which conducts research into aging and funds other anti-aging research projects at various universities. In 2013, Google announced Calico, a new company based in San Francisco that will harness new technologies to increase scientific understanding of the biology of aging. It is led by Arthur D. Levinson, and its research team includes scientists such as Hal V. Barron, David Botstein, and Cynthia Kenyon. In 2014, biologist Craig Venter founded Human Longevity Inc., a company dedicated to scientific research to end aging through genomics and cell therapy. They received funding with the goal of compiling a comprehensive human genotype, microbiome, and phenotype database.
Aside from private initiatives, aging research is being conducted in university laboratories, and includes universities such as Harvard and UCLA. University researchers have made a number of breakthroughs in extending the lives of mice and insects by reversing certain aspects of aging.
Ethics and politics
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.
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.
Though many scientists state 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.
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), Larry Page (co-founder of Google), Peter Diamandis, Sam Altman (CEO of OpenAI, invested in Retro Biosciences), and Brian Armstrong (founder of Coinbase and NewLimit).
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. 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."
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.
Transhumanist philosopher Nick Bostrom has argued that any technological advances in life extension must be equitably distributed and not restricted to a privileged few. 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.
Controversy about life extension is due to fear of overpopulation and possible effects on society. 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. 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.
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. 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.
Religious people are no more likely to oppose life extension than the unaffiliated, though some variation exists between religious denominations.
Aging as a disease
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." The two main arguments used are that aging is both inevitable and universal while diseases are not. 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. David Gems, assistant director of the Institute of Healthy Ageing, argues that aging should be viewed as a disease. 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. 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.
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.
Theoretically, extension of maximum lifespan in humans could be achieved by reducing the rate of aging damage by periodic replacement of damaged tissues, molecular repair or rejuvenation of deteriorated cells and tissues, reversal of harmful epigenetic changes, or the enhancement of enzyme telomerase activity.
Research geared towards life extension strategies in various organisms is currently under way at a number of academic and private institutions. Since 2009, investigators have found ways to increase the lifespan of nematode worms and yeast by 10-fold; the record in nematodes was achieved through genetic engineering and the extension in yeast by a combination of genetic engineering and caloric restriction. A 2009 review of longevity research noted: "Extrapolation from worms to mammals is risky at best, and it cannot be assumed that interventions will result in comparable life extension factors. Longevity gains from dietary restriction, or from mutations studied previously, yield smaller benefits to Drosophila than to nematodes, and smaller still to mammals. This is not unexpected, since mammals have evolved to live many times the worm's lifespan, and humans live nearly twice as long as the next longest-lived primate. From an evolutionary perspective, mammals and their ancestors have already undergone several hundred million years of natural selection favoring traits that could directly or indirectly favor increased longevity, and may thus have already settled on gene sequences that promote lifespan. Moreover, the very notion of a "life-extension factor" that could apply across taxa presumes a linear response rarely seen in biology."
There are a number of chemicals intended to slow the aging process currently being studied in animal models. 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. 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 and metformin for AMPK activation.
Sirtuin activating polyphenols, such as resveratrol and pterostilbene, and flavonoids, such as quercetin and fisetin, as well as oleic acid are dietary supplements that have also been studied in this context. Other popular supplements with less clear biological pathways to target aging include, lipoic acid, senolytics such as curcumin, and Coenzyme Q10. Daily low doses of ethanol as a potential supplement in spite of its highly negative hormesis response at higher doses has also been studied.
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 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.
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. 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.
Cloning and body part replacement
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. 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. 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. 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.
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.
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. It is regarded with skepticism within the mainstream scientific community and has been characterized as quackery.
Strategies for engineered negligible senescence
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.
While some biogerontologists find these ideas "worthy of discussion", others contend that the alleged benefits are too speculative given the current state of technology, referring to it as "fantasy rather than science".
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.
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.
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. 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.
In The Selfish Gene, Richard Dawkins describes an approach to life-extension that involves "fooling genes" into thinking the body is young. 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".
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. 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.
Some scientists believe that the dead may one day be "resurrected" through simulation technology.
Young blood injection
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. 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. 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" and that young blood treatments are "the scientific equivalent of fake news". The treatment appeared in HBO's Silicon Valley fiction series.
Two clinics in California, run by Jesse Karmazin and David C. Wright, 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.
- Advanced glycation end product
- Aging brain
- Aging movement control
- Alzheimer's disease
- Anti-aging movement
- Biological immortality
- Clinical Interventions in Aging
- DNA damage theory of aging
- Human enhancement
- Immortal DNA strand hypothesis
- Maximum lifespan
- Rejuvenation Research
- Slow aging
- Timeline of senescence research
- Transgenerational design
- Turner BS (2009). Can We Live Forever? A Sociological and Moral Inquiry. Anthem Press. p. 3.
- "agerasia". Oxford English Dictionary (Online ed.). Oxford University Press. (Subscription or participating institution membership required.)
- Japsen B (15 June 2009). "AMA report questions science behind using hormones as anti-aging treatment". The Chicago Tribune. Retrieved 17 July 2009.
- Holliday R (April 2009). "The extreme arrogance of anti-aging medicine". Biogerontology. 10 (2): 223–228. doi:10.1007/s10522-008-9170-6. PMID 18726707. S2CID 764136.
- Olshansky SJ, Hayflick L, Carnes BA (August 2002). "Position statement on human aging". The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences. 57 (8): B292–B297. doi:10.1093/gerona/57.8.B292. PMID 12145354.
- Warner H, Anderson J, Austad S, Bergamini E, Bredesen D, Butler R, et al. (November 2005). "Science fact and the SENS agenda. What can we reasonably expect from ageing research?". EMBO Reports. 6 (11): 1006–1008. doi:10.1038/sj.embor.7400555. PMC 1371037. PMID 16264422.
- López-Otín C, Blasco MA, Partridge L, Serrano M, Kroemer G (June 2013). "The hallmarks of aging". Cell. 153 (6): 1194–1217. doi:10.1016/j.cell.2013.05.039. PMC 3836174. PMID 23746838.
- Halliwell B, Gutteridge JMC (2007). Free Radicals in Biology and Medicine. Oxford University Press, USA, ISBN 019856869X, ISBN 978-0198568698
- Holmes GE, Bernstein C, Bernstein H (September 1992). "Oxidative and other DNA damages as the basis of aging: a review". Mutation Research. 275 (3–6): 305–315. doi:10.1016/0921-8734(92)90034-M. PMID 1383772.
- "Mouse Facts". informatics.jax.org.
- Pedro de Magalhães J (2014). "What Causes Aging? Damage-Based Theories of Aging".
- Verdaguer E, Junyent F, Folch J, Beas-Zarate C, Auladell C, Pallàs M, Camins A (March 2012). "Aging biology: a new frontier for drug discovery". Expert Opinion on Drug Discovery. 7 (3): 217–229. doi:10.1517/17460441.2012.660144. PMID 22468953. S2CID 24617426.
- Rauser CL, Mueller LD, Rose MR (February 2006). "The evolution of late life". Ageing Research Reviews. 5 (1): 14–32. doi:10.1016/j.arr.2005.06.003. PMID 16085467. S2CID 29623681.
- Stearns SC, Ackermann M, Doebeli M, Kaiser M (March 2000). "Experimental evolution of aging, growth, and reproduction in fruitflies". Proceedings of the National Academy of Sciences of the United States of America. 97 (7): 3309–3313. Bibcode:2000PNAS...97.3309S. doi:10.1073/pnas.060289597. PMC 16235. PMID 10716732.
- Newmark PA, Sánchez Alvarado A (March 2002). "Not your father's planarian: a classic model enters the era of functional genomics". Nature Reviews. Genetics. 3 (3): 210–219. doi:10.1038/nrg759. PMID 11972158. S2CID 28379017.
- Bavestrello G, Sommer C, Sarà M (1992). "Bi-directional conversion in Turritopsis nutricula (Hydrozoa)" (PDF). Scientia Marina. 56 (2–3): 137–140. Archived from the original (PDF) on 26 June 2015.
- Martínez DE (May 1998). "Mortality patterns suggest lack of senescence in hydra". Experimental Gerontology. 33 (3): 217–225. CiteSeerX 10.1.1.500.9508. doi:10.1016/S0531-5565(97)00113-7. PMID 9615920. S2CID 2009972.
- Petralia RS, Mattson MP, Yao PJ (July 2014). "Aging and longevity in the simplest animals and the quest for immortality". Ageing Research Reviews. 16: 66–82. doi:10.1016/j.arr.2014.05.003. PMC 4133289. PMID 24910306.
- Childs BG, Durik M, Baker DJ, van Deursen JM (December 2015). "Cellular senescence in aging and age-related disease: from mechanisms to therapy". Nature Medicine. 21 (12): 1424–1435. doi:10.1038/nm.4000. PMC 4748967. PMID 26646499.
- Kirkland JL, Tchkonia T (August 2015). "Clinical strategies and animal models for developing senolytic agents". Experimental Gerontology. 68: 19–25. doi:10.1016/j.exger.2014.10.012. PMC 4412760. PMID 25446976.
- van Deursen JM (May 2019). "Senolytic therapies for healthy longevity". Science. 364 (6441): 636–637. Bibcode:2019Sci...364..636V. doi:10.1126/science.aaw1299. PMC 6816502. PMID 31097655.
- Di Micco R, Krizhanovsky V, Baker D, d'Adda di Fagagna F (February 2021). "Cellular senescence in ageing: from mechanisms to therapeutic opportunities". Nature Reviews. Molecular Cell Biology. 22 (2): 75–95. doi:10.1038/s41580-020-00314-w. PMC 8344376. PMID 33328614.
- Robbins PD, Jurk D, Khosla S, Kirkland JL, LeBrasseur NK, Miller JD, et al. (January 2021). "Senolytic Drugs: Reducing Senescent Cell Viability to Extend Health Span". Annual Review of Pharmacology and Toxicology. 61 (1): 779–803. doi:10.1146/annurev-pharmtox-050120-105018. PMC 7790861. PMID 32997601.
- Dönertaş HM, Fuentealba M, Partridge L, Thornton JM (February 2019). "Identifying Potential Ageing-Modulating Drugs In Silico". Trends in Endocrinology and Metabolism. 30 (2): 118–131. doi:10.1016/j.tem.2018.11.005. PMC 6362144. PMID 30581056.
- Zhavoronkov A, Mamoshina P, Vanhaelen Q, Scheibye-Knudsen M, Moskalev A, Aliper A (January 2019). "Artificial intelligence for aging and longevity research: Recent advances and perspectives". Ageing Research Reviews. 49: 49–66. doi:10.1016/j.arr.2018.11.003. PMID 30472217. S2CID 53755842.
- Partridge L, Deelen J, Slagboom PE (September 2018). "Facing up to the global challenges of ageing". Nature. 561 (7721): 45–56. Bibcode:2018Natur.561...45P. doi:10.1038/s41586-018-0457-8. hdl:1887/75460. PMID 30185958. S2CID 52161707.
- Wong, Felix; Omori, Satotaka; Donghia, Nina M.; Zheng, Erica J.; Collins, James J. (4 May 2023). "Discovering small-molecule senolytics with deep neural networks". Nature Aging. 3 (6): 734–750. doi:10.1038/s43587-023-00415-z. ISSN 2662-8465. PMID 37142829. S2CID 258506382.
- Smer-Barreto, Vanessa; Quintanilla, Andrea; Elliott, Richard J. R.; Dawson, John C.; Sun, Jiugeng; Campa, Víctor M.; Lorente-Macías, Álvaro; Unciti-Broceta, Asier; Carragher, Neil O.; Acosta, Juan Carlos; Oyarzún, Diego A. (10 June 2023). "Discovery of senolytics using machine learning". Nature Communications. 14 (1): 3445. Bibcode:2023NatCo..14.3445S. doi:10.1038/s41467-023-39120-1. PMC 10257182. PMID 37301862.
- Partridge L, Fuentealba M, Kennedy BK (August 2020). "The quest to slow ageing through drug discovery". Nature Reviews. Drug Discovery. 19 (8): 513–532. doi:10.1038/s41573-020-0067-7. PMID 32467649. S2CID 218912510.
- Bonkowski MS, Sinclair DA (November 2016). "Slowing ageing by design: the rise of NAD+ and sirtuin-activating compounds". Nature Reviews. Molecular Cell Biology. 17 (11): 679–690. doi:10.1038/nrm.2016.93. PMC 5107309. PMID 27552971.
- Sekhar RV (December 2021). "GlyNAC Supplementation Improves Glutathione Deficiency, Oxidative Stress, Mitochondrial Dysfunction, Inflammation, Aging Hallmarks, Metabolic Defects, Muscle Strength, Cognitive Decline, and Body Composition: Implications for Healthy Aging". The Journal of Nutrition. 151 (12): 3606–3616. doi:10.1093/jn/nxab309. PMID 34587244.
- McIntyre RL, Liu YJ, Hu M, Morris BJ, Willcox BJ, Donlon TA, et al. (June 2022). "Pharmaceutical and nutraceutical activation of FOXO3 for healthy longevity". Ageing Research Reviews. 78: 101621. doi:10.1016/j.arr.2022.101621. PMID 35421606. S2CID 248089515.
- Kirkland JL, Tchkonia T (November 2020). "Senolytic drugs: from discovery to translation". Journal of Internal Medicine. 288 (5): 518–536. doi:10.1111/joim.13141. PMC 7405395. PMID 32686219.
- Palmer AK, Gustafson B, Kirkland JL, Smith U (October 2019). "Cellular senescence: at the nexus between ageing and diabetes". Diabetologia. 62 (10): 1835–1841. doi:10.1007/s00125-019-4934-x. PMC 6731336. PMID 31451866.
- Blagosklonny MV (August 2019). "Fasting and rapamycin: diabetes versus benevolent glucose intolerance". Cell Death & Disease. 10 (8): 607. doi:10.1038/s41419-019-1822-8. PMC 6690951. PMID 31406105.
- Martel J, Chang SH, Wu CY, Peng HH, Hwang TL, Ko YF, et al. (March 2021). "Recent advances in the field of caloric restriction mimetics and anti-aging molecules". Ageing Research Reviews. 66: 101240. doi:10.1016/j.arr.2020.101240. PMID 33347992. S2CID 229351578.
- Bjelakovic G, Nikolova D, Gluud LL, Simonetti RG, Gluud C (February 2007). "Mortality in randomized trials of antioxidant supplements for primary and secondary prevention: systematic review and meta-analysis". JAMA. 297 (8): 842–857. doi:10.1001/jama.297.8.842. PMID 17327526.
- Bjelakovic G, Nikolova D, Gluud LL, Simonetti RG, Gluud C (March 2012). "Antioxidant supplements for prevention of mortality in healthy participants and patients with various diseases". The Cochrane Database of Systematic Reviews. 2012 (3): CD007176. doi:10.1002/14651858.CD007176.pub2. hdl:10138/136201. PMC 8407395. PMID 22419320.
- Jiang S, Pan Z, Li H, Li F, Song Y, Qiu Y (2014). "Meta-analysis: low-dose intake of vitamin E combined with other vitamins or minerals may decrease all-cause mortality". Journal of Nutritional Science and Vitaminology. 60 (3): 194–205. doi:10.3177/jnsv.60.194. PMID 25078376.
Neither vitamin E intake alone nor combined with other agents is associated with a reduction in all-cause mortality.
- Garay RP (July 2021). "Investigational drugs and nutrients for human longevity. Recent clinical trials registered in ClinicalTrials.gov and clinicaltrialsregister.eu". Expert Opinion on Investigational Drugs. 30 (7): 749–758. doi:10.1080/13543784.2021.1939306. PMID 34081543. S2CID 235334397.
- Damiano S, Muscariello E, La Rosa G, Di Maro M, Mondola P, Santillo M (August 2019). "Dual Role of Reactive Oxygen Species in Muscle Function: Can Antioxidant Dietary Supplements Counteract Age-Related Sarcopenia?". International Journal of Molecular Sciences. 20 (15): E3815. doi:10.3390/ijms20153815. PMC 6696113. PMID 31387214.
- Badran A, Nasser SA, Mesmar J, El-Yazbi AF, Bitto A, Fardoun MM, et al. (November 2020). "Reactive Oxygen Species: Modulators of Phenotypic Switch of Vascular Smooth Muscle Cells". International Journal of Molecular Sciences. 21 (22): 8764. doi:10.3390/ijms21228764. PMC 7699590. PMID 33233489.
- Sohal RS, Orr WC (February 2012). "The redox stress hypothesis of aging". Free Radical Biology & Medicine. 52 (3): 539–555. doi:10.1016/j.freeradbiomed.2011.10.445. PMC 3267846. PMID 22080087.
- McCarty MF, O'Keefe JH, DiNicolantonio JJ (2018). "Dietary Glycine Is Rate-Limiting for Glutathione Synthesis and May Have Broad Potential for Health Protection". The Ochsner Journal. 18 (1): 81–87. PMC 5855430. PMID 29559876.
- Griffiths HR (November 2000). "Antioxidants and protein oxidation". Free Radical Research. 33 (Supplement): S47–S58. PMID 11191275.
- Cobley JN (September 2020). "Mechanisms of Mitochondrial ROS Production in Assisted Reproduction: The Known, the Unknown, and the Intriguing". Antioxidants. 9 (10): 933. doi:10.3390/antiox9100933. PMC 7599503. PMID 33003362.
- Bast, A.; Haenen GRMM; Lamprecht, M. (2015). "Nutritional Antioxidants: It Is Time to Categorise". Antioxidants in Sport Nutrition. CRC Press/Taylor & Francis. ISBN 9781466567573. PMID 26065087.
- Lobo, V; Patil, A; Phatak, A; Chandra, N (2010). "Free radicals, antioxidants and functional foods: Impact on human health". Pharmacognosy Reviews. 4 (8): 118–126. doi:10.4103/0973-7847.70902. PMC 3249911. PMID 22228951.
- Hood WR, Zhang Y, Mowry AV, Hyatt HW, Kavazis AN (September 2018). "Life History Trade-offs within the Context of Mitochondrial Hormesis". Integrative and Comparative Biology. 58 (3): 567–577. doi:10.1093/icb/icy073. PMC 6145418. PMID 30011013.
- Lee MB, Hill CM, Bitto A, Kaeberlein M (November 2021). "Antiaging diets: Separating fact from fiction". Science. 374 (6570): eabe7365. doi:10.1126/science.abe7365. PMC 8841109. PMID 34793210.
- Dominguez LJ, Di Bella G, Veronese N, Barbagallo M (June 2021). "Impact of Mediterranean Diet on Chronic Non-Communicable Diseases and Longevity". Nutrients. 13 (6): 2028. doi:10.3390/nu13062028. PMC 8231595. PMID 34204683.
- Eleftheriou D, Benetou V, Trichopoulou A, La Vecchia C, Bamia C (November 2018). "Mediterranean diet and its components in relation to all-cause mortality: meta-analysis". The British Journal of Nutrition. 120 (10): 1081–1097. doi:10.1017/S0007114518002593. PMID 30401007. S2CID 53226475.
- Ekmekcioglu C (2020). "Nutrition and longevity - From mechanisms to uncertainties". Critical Reviews in Food Science and Nutrition. 60 (18): 3063–3082. doi:10.1080/10408398.2019.1676698. PMID 31631676. S2CID 204815279.
- "What Do We Know About Healthy Aging?". National Institute on Aging. Retrieved 1 June 2022.
- Hidalgo-Mora JJ, García-Vigara A, Sánchez-Sánchez ML, García-Pérez MÁ, Tarín J, Cano A (February 2020). "The Mediterranean diet: A historical perspective on food for health". Maturitas. 132: 65–69. doi:10.1016/j.maturitas.2019.12.002. PMID 31883665. S2CID 209510802.
- Vasto S, Barera A, Rizzo C, Di Carlo M, Caruso C, Panotopoulos G (2014). "Mediterranean diet and longevity: an example of nutraceuticals?". Current Vascular Pharmacology. 12 (5): 735–738. doi:10.2174/1570161111666131219111818. PMID 24350926.
- Willcox DC, Scapagnini G, Willcox BJ (March 2014). "Healthy aging diets other than the Mediterranean: a focus on the Okinawan diet". Mechanisms of Ageing and Development. 136–137: 148–162. doi:10.1016/j.mad.2014.01.002. PMC 5403516. PMID 24462788.
- Si H, Lai CQ, Liu D (2021). "Dietary Epicatechin, A Novel Anti-aging Bioactive Small Molecule". Current Medicinal Chemistry. 28 (1): 3–18. doi:10.2174/0929867327666191230104958. PMID 31886745. S2CID 209510438.
- Solon-Biet SM, Mitchell SJ, de Cabo R, Raubenheimer D, Le Couteur DG, Simpson SJ (July 2015). "Macronutrients and caloric intake in health and longevity". The Journal of Endocrinology. 226 (1): R17–R28. doi:10.1530/JOE-15-0173. PMC 4490104. PMID 26021555. S2CID 13785596.
- Longo VD, Anderson RM (April 2022). "Nutrition, longevity and disease: From molecular mechanisms to interventions". Cell. 185 (9): 1455–1470. doi:10.1016/j.cell.2022.04.002. PMC 9089818. PMID 35487190.
- Tsugane S (June 2021). "Why has Japan become the world's most long-lived country: insights from a food and nutrition perspective". European Journal of Clinical Nutrition. 75 (6): 921–928. doi:10.1038/s41430-020-0677-5. PMC 8189904. PMID 32661353.
- Badal VD, Vaccariello ED, Murray ER, Yu KE, Knight R, Jeste DV, Nguyen TT (December 2020). "The Gut Microbiome, Aging, and Longevity: A Systematic Review". Nutrients. 12 (12): 3759. doi:10.3390/nu12123759. PMC 7762384. PMID 33297486.
- Coman V, Vodnar DC (November 2020). "Gut microbiota and old age: Modulating factors and interventions for healthy longevity". Experimental Gerontology. 141: 111095. doi:10.1016/j.exger.2020.111095. PMC 7510636. PMID 32979504.
- DeJong EN, Surette MG, Bowdish DM (August 2020). "The Gut Microbiota and Unhealthy Aging: Disentangling Cause from Consequence". Cell Host & Microbe. 28 (2): 180–189. doi:10.1016/j.chom.2020.07.013. PMID 32791111. S2CID 221127637.
- Low DY, Hejndorf S, Tharmabalan RT, Poppema S, Pettersson S (2021). "Regional Diets Targeting Gut Microbial Dynamics to Support Prolonged Healthspan". Frontiers in Microbiology. 12: 659465. doi:10.3389/fmicb.2021.659465. PMC 8116520. PMID 33995322.
- Warman DJ, Jia H, Kato H (February 2022). "The Potential Roles of Probiotics, Resistant Starch, and Resistant Proteins in Ameliorating Inflammation during Aging (Inflammaging)". Nutrients. 14 (4): 747. doi:10.3390/nu14040747. PMC 8879781. PMID 35215397.
- Trush EA, Poluektova EA, Beniashvilli AG, Shifrin OS, Poluektov YM, Ivashkin VT (December 2020). "The Evolution of Human Probiotics: Challenges and Prospects". Probiotics and Antimicrobial Proteins. 12 (4): 1291–1299. doi:10.1007/s12602-019-09628-4. PMID 31907861. S2CID 209893272.
- Fadnes LT, Økland JM, Haaland ØA, Johansson KA (February 2022). "Estimating impact of food choices on life expectancy: A modeling study". PLOS Medicine. 19 (2): e1003889. doi:10.1371/journal.pmed.1003889. PMC 8824353. PMID 35134067. S2CID 246676734. Lay summary: "Changing your diet could add up to a decade to life expectancy, study finds". Public Library of Science. Retrieved 16 March 2022.
- Mariotti F, Gardner CD (November 2019). "Dietary Protein and Amino Acids in Vegetarian Diets-A Review". Nutrients. 11 (11): 2661. doi:10.3390/nu11112661. PMC 6893534. PMID 31690027.
- Fong BY, Chiu WK, Chan WF, Lam TY (July 2021). "A Review Study of a Green Diet and Healthy Ageing". International Journal of Environmental Research and Public Health. 18 (15): 8024. doi:10.3390/ijerph18158024. PMC 8345706. PMID 34360317.
- Parlasca MC, Qaim M (5 October 2022). "Meat Consumption and Sustainability". Annual Review of Resource Economics. 14: 17–41. doi:10.1146/annurev-resource-111820-032340. ISSN 1941-1340.
- Sikand G, Severson T (December 2020). "Top 10 dietary strategies for atherosclerotic cardiovascular risk reduction". American Journal of Preventive Cardiology. 4: 100106. doi:10.1016/j.ajpc.2020.100106. PMC 8315554. PMID 34327475.
- Bhatti SK, O'Keefe JH, Lavie CJ (November 2013). "Coffee and tea: perks for health and longevity?". Current Opinion in Clinical Nutrition and Metabolic Care. 16 (6): 688–697. doi:10.1097/MCO.0b013e328365b9a0. PMID 24071782. S2CID 30244976.
- Singh RB, Fedacko J, Fatima G, Magomedova A, Watanabe S, Elkilany G (February 2022). "Why and How the Indo-Mediterranean Diet May Be Superior to Other Diets: The Role of Antioxidants in the Diet". Nutrients. 14 (4): 898. doi:10.3390/nu14040898. PMC 8879532. PMID 35215548.
- Fan J, Feng Z, Chen N (September 2020). "Spermidine as a target for cancer therapy". Pharmacological Research. 159: 104943. doi:10.1016/j.phrs.2020.104943. PMID 32461185. S2CID 218976561.
- Muñoz-Esparza NC, Latorre-Moratalla ML, Comas-Basté O, Toro-Funes N, Veciana-Nogués MT, Vidal-Carou MC (2019). "Polyamines in Food". Frontiers in Nutrition. 6: 108. doi:10.3389/fnut.2019.00108. PMC 6637774. PMID 31355206.
- Madeo F, Eisenberg T, Büttner S, Ruckenstuhl C, Kroemer G (January 2010). "Spermidine: a novel autophagy inducer and longevity elixir". Autophagy. 6 (1): 160–162. doi:10.4161/auto.6.1.10600. PMID 20110777. S2CID 36422896.
- Hofer SJ, Davinelli S, Bergmann M, Scapagnini G, Madeo F (2021). "Caloric Restriction Mimetics in Nutrition and Clinical Trials". Frontiers in Nutrition. 8: 717343. doi:10.3389/fnut.2021.717343. PMC 8450594. PMID 34552954.
- Madeo F, Hofer SJ, Pendl T, Bauer MA, Eisenberg T, Carmona-Gutierrez D, Kroemer G (September 2020). "Nutritional Aspects of Spermidine". Annual Review of Nutrition. 40 (1): 135–159. doi:10.1146/annurev-nutr-120419-015419. PMID 32634331. S2CID 220408668.
- Gómez-Linton DR, Alavez S, Alarcón-Aguilar A, López-Diazguerrero NE, Konigsberg M, Pérez-Flores LJ (October 2019). "Some naturally occurring compounds that increase longevity and stress resistance in model organisms of aging". Biogerontology. 20 (5): 583–603. doi:10.1007/s10522-019-09817-2. PMID 31187283. S2CID 184483900.
- Cichońska P, Ziarno M (December 2021). "Legumes and Legume-Based Beverages Fermented with Lactic Acid Bacteria as a Potential Carrier of Probiotics and Prebiotics". Microorganisms. 10 (1): 91. doi:10.3390/microorganisms10010091. PMC 8779895. PMID 35056540.
- Ashwar BA, Gani A, Shah A, Wani IA, Masoodi FA (April 2016). "Preparation, health benefits and applications of resistant starch-a review: Resistant starch-a review". Starch - Stärke. 68 (3–4): 287–301. doi:10.1002/star.201500064.
- Bojarczuk A, Skąpska S, Khaneghah AM, Marszałek K (1 June 2022). "Health benefits of resistant starch: A review of the literature". Journal of Functional Foods. 93: 105094. doi:10.1016/j.jff.2022.105094. ISSN 1756-4646. S2CID 248593252.
- Griswold, Max G.; et al. (September 2018). "Alcohol use and burden for 195 countries and territories, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016". Lancet. 392 (10152): 1015–1035. doi:10.1016/S0140-6736(18)31310-2. PMC 6148333. PMID 30146330.
- "Facts about moderate drinking | CDC". www.cdc.gov. 19 April 2022.
- Giacosa A, Barale R, Bavaresco L, Faliva MA, Gerbi V, La Vecchia C, et al. (2016). "Mediterranean Way of Drinking and Longevity". Critical Reviews in Food Science and Nutrition. 56 (4): 635–640. doi:10.1080/10408398.2012.747484. PMID 25207479. S2CID 35609367.
- Heiss C, Spyridopoulos I, Haendeler J (August 2018). "Interventions to slow cardiovascular aging: Dietary restriction, drugs and novel molecules". Experimental Gerontology. 109: 108–118. doi:10.1016/j.exger.2017.06.015. PMID 28658611. S2CID 38595578.
- Capurso C (July 2021). "Whole-Grain Intake in the Mediterranean Diet and a Low Protein to Carbohydrates Ratio Can Help to Reduce Mortality from Cardiovascular Disease, Slow Down the Progression of Aging, and to Improve Lifespan: A Review". Nutrients. 13 (8): 2540. doi:10.3390/nu13082540. PMC 8401068. PMID 34444699.
- Widmer RJ, Flammer AJ, Lerman LO, Lerman A (March 2015). "The Mediterranean diet, its components, and cardiovascular disease". The American Journal of Medicine. 128 (3): 229–238. doi:10.1016/j.amjmed.2014.10.014. PMC 4339461. PMID 25447615.
- Ventriglio A, Sancassiani F, Contu MP, Latorre M, Di Slavatore M, Fornaro M, Bhugra D (2020). "Mediterranean Diet and its Benefits on Health and Mental Health: A Literature Review". Clinical Practice and Epidemiology in Mental Health. 16 (Suppl-1): 156–164. doi:10.2174/1745017902016010156. PMC 7536728. PMID 33029192.
- Mazzocchi A, Leone L, Agostoni C, Pali-Schöll I (December 2019). "The Secrets of the Mediterranean Diet. Does [Only] Olive Oil Matter?". Nutrients. 11 (12): E2941. doi:10.3390/nu11122941. PMC 6949890. PMID 31817038.
- Ramadas A, Tham SM, Lalani SA, Shyam S (April 2021). "Diet Quality of Malaysians across Lifespan: A Scoping Review of Evidence in a Multi-Ethnic Population". Nutrients. 13 (4): 1380. doi:10.3390/nu13041380. PMC 8074191. PMID 33924050.
- D'Auria E, Peroni DG, Sartorio MU, Verduci E, Zuccotti GV, Venter C (15 September 2020). "The Role of Diet Diversity and Diet Indices on Allergy Outcomes". Frontiers in Pediatrics. 8: 545. doi:10.3389/fped.2020.00545. PMC 7522364. PMID 33042906.
- Campisi J, Kapahi P, Lithgow GJ, Melov S, Newman JC, Verdin E (July 2019). "From discoveries in ageing research to therapeutics for healthy ageing". Nature. 571 (7764): 183–192. Bibcode:2019Natur.571..183C. doi:10.1038/s41586-019-1365-2. PMC 7205183. PMID 31292558.
- Sachdeva V, Roy A, Bharadvaja N (2020). "Current Prospects of Nutraceuticals: A Review". Current Pharmaceutical Biotechnology. 21 (10): 884–896. doi:10.2174/1389201021666200130113441. PMID 32000642. S2CID 210982161.
- Craig WJ (December 2010). "Nutrition concerns and health effects of vegetarian diets". Nutrition in Clinical Practice. 25 (6): 613–620. doi:10.1177/0884533610385707. PMID 21139125.
- Barbagallo M, Veronese N, Dominguez LJ (January 2021). "Magnesium in Aging, Health and Diseases". Nutrients. 13 (2): 463. doi:10.3390/nu13020463. PMC 7912123. PMID 33573164.
- Meccariello R, D'Angelo S (March 2021). "Impact of Polyphenolic-Food on Longevity: An Elixir of Life. An Overview". Antioxidants. 10 (4): 507. doi:10.3390/antiox10040507. PMC 8064059. PMID 33805092.
- Finicelli M, Squillaro T, Di Cristo F, Di Salle A, Melone MA, Galderisi U, Peluso G (May 2019). "Metabolic syndrome, Mediterranean diet, and polyphenols: Evidence and perspectives". Journal of Cellular Physiology. 234 (5): 5807–5826. doi:10.1002/jcp.27506. PMID 30317573. S2CID 52982690.
- Li YR, Li S, Lin CC (January 2018). "Effect of resveratrol and pterostilbene on aging and longevity". BioFactors. 44 (1): 69–82. doi:10.1002/biof.1400. PMID 29210129. S2CID 19252691.
- Leri M, Scuto M, Ontario ML, Calabrese V, Calabrese EJ, Bucciantini M, Stefani M (February 2020). "Healthy Effects of Plant Polyphenols: Molecular Mechanisms". International Journal of Molecular Sciences. 21 (4): 1250. doi:10.3390/ijms21041250. PMC 7072974. PMID 32070025.
- Yessenkyzy A, Saliev T, Zhanaliyeva M, Masoud AR, Umbayev B, Sergazy S, et al. (May 2020). "Polyphenols as Caloric-Restriction Mimetics and Autophagy Inducers in Aging Research". Nutrients. 12 (5): 1344. doi:10.3390/nu12051344. PMC 7285205. PMID 32397145.
- Panossian A, Wikman G, Sarris J (June 2010). "Rosenroot (Rhodiola rosea): traditional use, chemical composition, pharmacology and clinical efficacy". Phytomedicine. 17 (7): 481–493. doi:10.1016/j.phymed.2010.02.002. PMID 20378318.
- Chattopadhyay D, Thirumurugan K (April 2018). "Longevity promoting efficacies of different plant extracts in lower model organisms". Mechanisms of Ageing and Development. 171: 47–57. doi:10.1016/j.mad.2018.03.002. PMID 29526449. S2CID 3871898.
- Li S, Laher I (December 2015). "Exercise Pills: At the Starting Line". Trends in Pharmacological Sciences. 36 (12): 906–917. doi:10.1016/j.tips.2015.08.014. PMID 26439443.
- Cheng CK, Luo JY, Lau CW, Chen ZY, Tian XY, Huang Y (March 2020). "Pharmacological basis and new insights of resveratrol action in the cardiovascular system". British Journal of Pharmacology. 177 (6): 1258–1277. doi:10.1111/bph.14801. PMC 7056472. PMID 31347157.
- Handschin C (1 January 2016). "Caloric restriction and exercise "mimetics": Ready for prime time?". Pharmacological Research. 103: 158–166. doi:10.1016/j.phrs.2015.11.009. ISSN 1043-6618. PMC 4970791. PMID 26658171.
- McCubrey JA, Lertpiriyapong K, Steelman LS, Abrams SL, Yang LV, Murata RM, et al. (June 2017). "Effects of resveratrol, curcumin, berberine and other nutraceuticals on aging, cancer development, cancer stem cells and microRNAs". Aging. 9 (6): 1477–1536. doi:10.18632/aging.101250. PMC 5509453. PMID 28611316.
- DiNicolantonio JJ, McCarty MF, Assanga SI, Lujan LL, O'Keefe JH (March 2022). "Ferulic acid and berberine, via Sirt1 and AMPK, may act as cell cleansing promoters of healthy longevity". Open Heart. 9 (1): e001801. doi:10.1136/openhrt-2021-001801. PMC 8932268. PMID 35301252.
- McCarty MF (April 2014). "AMPK activation--protean potential for boosting healthspan". Age. 36 (2): 641–663. doi:10.1007/s11357-013-9595-y. PMC 4039279. PMID 24248330.
- McCormack D, McFadden D (2013). "A review of pterostilbene antioxidant activity and disease modification". Oxidative Medicine and Cellular Longevity. 2013: 575482. doi:10.1155/2013/575482. PMC 3649683. PMID 23691264.
- Lee SH, Lee JH, Lee HY, Min KJ (January 2019). "Sirtuin signaling in cellular senescence and aging". BMB Reports. 52 (1): 24–34. doi:10.5483/BMBRep.2019.52.1.290. PMC 6386230. PMID 30526767. S2CID 54476239.
- McClements DJ, Saliva-Trujillo L, Zhang R, Zhang Z, Zou L, Yao M, Xiao H (October 2016). "Boosting the bioavailability of hydrophobic nutrients, vitamins, and nutraceuticals in natural products using excipient emulsions". Food Research International. 88 (Pt A): 140–152. doi:10.1016/j.foodres.2015.11.017. PMID 28847393.
- Hu B, Liu X, Zhang C, Zeng X (January 2017). "Food macromolecule based nanodelivery systems for enhancing the bioavailability of polyphenols". Journal of Food and Drug Analysis. 25 (1): 3–15. doi:10.1016/j.jfda.2016.11.004. PMC 9333428. PMID 28911541.
- Delhove J, Osenk I, Prichard I, Donnelley M (January 2020). "Public Acceptability of Gene Therapy and Gene Editing for Human Use: A Systematic Review". Human Gene Therapy. 31 (1–2): 20–46. doi:10.1089/hum.2019.197. PMID 31802714. S2CID 208645665.
- Beyret E, Martinez Redondo P, Platero Luengo A, Izpisua Belmonte JC (January 2018). "Elixir of Life: Thwarting Aging With Regenerative Reprogramming". Circulation Research. 122 (1): 128–141. doi:10.1161/CIRCRESAHA.117.311866. PMC 5823281. PMID 29301845.
- Yener Ilce B, Cagin U, Yilmazer A (March 2018). "Cellular reprogramming: A new way to understand aging mechanisms". Wiley Interdisciplinary Reviews. Developmental Biology. 7 (2). doi:10.1002/wdev.308. PMID 29350802. S2CID 46743444.
- Topart C, Werner E, Arimondo PB (July 2020). "Wandering along the epigenetic timeline". Clinical Epigenetics. 12 (1): 97. doi:10.1186/s13148-020-00893-7. PMC 7330981. PMID 32616071.
- Ullah M, Sun Z (January 2018). "Stem cells and anti-aging genes: double-edged sword-do the same job of life extension". Stem Cell Research & Therapy. 9 (1): 3. doi:10.1186/s13287-017-0746-4. PMC 5763529. PMID 29321045.
- Baraniak, Priya R; McDevitt, Todd C (January 2010). "Stem cell paracrine actions and tissue regeneration". Regenerative Medicine. 5 (1): 121–143. doi:10.2217/rme.09.74. PMC 2833273. PMID 20017699.
- Rzigalinski BA, Meehan K, Davis RM, Xu Y, Miles WC, Cohen CA (December 2006). "Radical nanomedicine". Nanomedicine. 1 (4): 399–412. doi:10.2217/174358184.108.40.2069. PMID 17716143.
- Ventola, CL (October 2012). "The nanomedicine revolution: part 2: current and future clinical applications". P & T: A Peer-Reviewed Journal for Formulary Management. 37 (10): 582–91. PMC 3474440. PMID 23115468.
- Khorraminejad-Shirazi M, Dorvash M, Estedlal A, Hoveidaei AH, Mazloomrezaei M, Mosaddeghi P (October 2019). "Aging: A cell source limiting factor in tissue engineering". World Journal of Stem Cells. 11 (10): 787–802. doi:10.4252/wjsc.v11.i10.787. PMC 6828594. PMID 31692986. S2CID 207894219.
- Chow LS, Gerszten RE, Taylor JM, Pedersen BK, van Praag H, Trappe S, et al. (May 2022). "Exerkines in health, resilience and disease". Nature Reviews. Endocrinology. 18 (5): 273–289. doi:10.1038/s41574-022-00641-2. PMC 9554896. PMID 35304603. S2CID 247524287.
- Nederveen JP, Warnier G, Di Carlo A, Nilsson MI, Tarnopolsky MA (2020). "Extracellular Vesicles and Exosomes: Insights From Exercise Science". Frontiers in Physiology. 11: 604274. doi:10.3389/fphys.2020.604274. PMC 7882633. PMID 33597890.
- Lananna BV, Imai SI (October 2021). "Friends and foes: Extracellular vesicles in aging and rejuvenation". FASEB BioAdvances. 3 (10): 787–801. doi:10.1096/fba.2021-00077. PMC 8493967. PMID 34632314.
- López-Otín C, Galluzzi L, Freije JM, Madeo F, Kroemer G (August 2016). "Metabolic Control of Longevity". Cell. 166 (4): 802–821. doi:10.1016/j.cell.2016.07.031. PMID 27518560. S2CID 2316555.
- Tomita K, Kuwahara Y, Igarashi K, Roudkenar MH, Roushandeh AM, Kurimasa A, Sato T (August 2021). "Mitochondrial Dysfunction in Diseases, Longevity, and Treatment Resistance: Tuning Mitochondria Function as a Therapeutic Strategy". Genes. 12 (9): 1348. doi:10.3390/genes12091348. PMC 8467098. PMID 34573330.
- Akbari M, Kirkwood TB, Bohr VA (September 2019). "Mitochondria in the signaling pathways that control longevity and health span". Ageing Research Reviews. 54: 100940. doi:10.1016/j.arr.2019.100940. PMC 7479635. PMID 31415807.
- Akbari M, Kirkwood TB, Bohr VA (September 2019). "Mitochondria in the signaling pathways that control longevity and health span". Ageing Research Reviews. 54: 100940. doi:10.1016/j.arr.2019.100940. PMC 7479635. PMID 31415807. S2CID 199544098.
- Santoro A, Martucci M, Conte M, Capri M, Franceschi C, Salvioli S (December 2020). "Inflammaging, hormesis and the rationale for anti-aging strategies". Ageing Research Reviews. 64: 101142. doi:10.1016/j.arr.2020.101142. PMID 32814129. S2CID 221136388.
- Ingram DK, Chefer S, Matochik J, Moscrip TD, Weed J, Roth GS, et al. (April 2001). "Aging and caloric restriction in nonhuman primates: behavioral and in vivo brain imaging studies". Annals of the New York Academy of Sciences. 928: 316–326. doi:10.1111/j.1749-6632.2001.tb05661.x. PMID 11795523. S2CID 35478202.
- Cardoso AL, Fernandes A, Aguilar-Pimentel JA, de Angelis MH, Guedes JR, Brito MA, et al. (November 2018). "Towards frailty biomarkers: Candidates from genes and pathways regulated in aging and age-related diseases". Ageing Research Reviews. 47: 214–277. doi:10.1016/j.arr.2018.07.004. PMID 30071357. S2CID 51865989.
- Sattler FR (August 2013). "Growth hormone in the aging male". Best Practice & Research. Clinical Endocrinology & Metabolism. 27 (4): 541–555. doi:10.1016/j.beem.2013.05.003. PMC 3940699. PMID 24054930.
In animal models, alterations in GH/IGF-1 signaling with reductions in these somatotrophs appear to increase life span. ... Administration of IGF-1Eb (mechanogrowth factor) stimulates proliferation of myoblasts and induces muscle hypertrophy. Increases in GH and IGF-1 during adolescence are beneficial for brain and cardiovascular function during the aging process and GH administration during adolescence is vasoprotective and increases life-span.15 ... Studies relating GH and IGF-1 status to longevity provide inconsistent evidence as to whether decreased (somatopause) or high levels (e.g. acromegaly) of these hormones are beneficial or detrimental to longevity. ... It is difficult to reconcile the largely protective effects of GH/IGF-1 deficiency on longevity in animals with the inconsistent or deleterious effects of low levels or declining GH/IGF-1 during human aging.
- Baranowska B, Kochanowski J (September 2020). "The metabolic, neuroprotective cardioprotective and antitumor effects of the Klotho protein". Neuro Endocrinology Letters. 41 (2): 69–75. PMID 33185993.
- Fossati C, Papalia R, Torre G, Vadalà G, Borrione P, Grazioli E, et al. (July 2020). "Frailty of the elderly in orthopaedic surgery and body composition changes: the musculoskeletal crosstalk through irisin". Journal of Biological Regulators and Homeostatic Agents. 34 (4 Suppl. 3): 327–335. Congress of the Italian Orthopaedic Research Society. PMID 33261297.
- Vila J (2021). "Social Support and Longevity: Meta-Analysis-Based Evidence and Psychobiological Mechanisms". Frontiers in Psychology. 12: 717164. doi:10.3389/fpsyg.2021.717164. PMC 8473615. PMID 34589025.
- O'Keefe EL, Torres-Acosta N, O'Keefe JH, Lavie CJ (July 2020). "Training for Longevity: The Reverse J-Curve for Exercise". Missouri Medicine. 117 (4): 355–361. PMC 7431070. PMID 32848273.
Current studies suggest that 2.5 to 5 hours/week of moderate or vigorous physical activity will confer maximal benefits; >10 hours/week may reduce these health benefits.
- Min S, Masanovic B, Bu T, Matic RM, Vasiljevic I, Vukotic M, et al. (2 December 2021). "The Association Between Regular Physical Exercise, Sleep Patterns, Fasting, and Autophagy for Healthy Longevity and Well-Being: A Narrative Review". Frontiers in Psychology. 12: 803421. doi:10.3389/fpsyg.2021.803421. PMC 8674197. PMID 34925198.
- Hofer SJ, Davinelli S, Bergmann M, Scapagnini G, Madeo F (2021). "Caloric Restriction Mimetics in Nutrition and Clinical Trials". Frontiers in Nutrition. 8: 717343. doi:10.3389/fnut.2021.717343. PMC 8450594. PMID 34552954.
- Chapman BP, Roberts B, Duberstein P (10 July 2011). "Personality and longevity: knowns, unknowns, and implications for public health and personalized medicine". Journal of Aging Research. 2011: 759170. doi:10.4061/2011/759170. PMC 3134197. PMID 21766032. S2CID 16615606.
- Kern ML, Friedman HS (September 2008). "Do conscientious individuals live longer? A quantitative review". Health Psychology. 27 (5): 505–512. doi:10.1037/0278-6220.127.116.115. PMID 18823176.
- Froy O, Miskin R (December 2010). "Effect of feeding regimens on circadian rhythms: implications for aging and longevity". Aging. 2 (1): 7–27. doi:10.18632/aging.100116. PMC 2837202. PMID 20228939.
- Froy O (August 2011). "Circadian rhythms, aging, and life span in mammals". Physiology. 26 (4): 225–235. doi:10.1152/physiol.00012.2011. PMID 21841071.
- Acosta-Rodríguez VA, Rijo-Ferreira F, Green CB, Takahashi JS (May 2021). "Importance of circadian timing for aging and longevity". Nature Communications. 12 (1): 2862. Bibcode:2021NatCo..12.2862A. doi:10.1038/s41467-021-22922-6. PMC 8129076. PMID 34001884. S2CID 234770669.
- Post SG (2005). "Altuism, happiness, and health: it's good to be good". International Journal of Behavioral Medicine. 12 (2): 66–77. doi:10.1207/s15327558ijbm1202_4. PMID 15901215. S2CID 12544814.
- Gottlieb BH, Gillespie AA (2008). "Volunteerism, health, and civic engagement among older adults". Canadian Journal on Aging. 27 (4): 399–406. doi:10.3138/cja.27.4.399. PMID 19416800. S2CID 24698644.
- Diener E, Oishi S, Tay L (April 2018). "Advances in subjective well-being research". Nature Human Behaviour. 2 (4): 253–260. doi:10.1038/s41562-018-0307-6. PMID 30936533. S2CID 4726262.
- Gomez CR (October 2021). "Role of heat shock proteins in aging and chronic inflammatory diseases". GeroScience. 43 (5): 2515–2532. doi:10.1007/s11357-021-00394-2. PMC 8599533. PMID 34241808.
- Seals DR, Justice JN, LaRocca TJ (April 2016). "Physiological geroscience: targeting function to increase healthspan and achieve optimal longevity". The Journal of Physiology. 594 (8): 2001–2024. doi:10.1113/jphysiol.2014.282665. PMC 4933122. PMID 25639909. S2CID 9776021.
- Roser M (26 May 2017). "Link between health spending and life expectancy: US is an outlier". Our World in Data. Click the sources tab under the chart for info on the countries, healthcare expenditures, and data sources. See the later version of the chart here.
- Lelieveld J, Pozzer A, Pöschl U, Fnais M, Haines A, Münzel T (September 2020). "Loss of life expectancy from air pollution compared to other risk factors: a worldwide perspective". Cardiovascular Research. 116 (11): 1910–1917. doi:10.1093/cvr/cvaa025. PMC 7449554. PMID 32123898.
- Murphy KJ, Parletta N (May 2018). "Implementing a Mediterranean-Style Diet Outside the Mediterranean Region". Current Atherosclerosis Reports. 20 (6): 28. doi:10.1007/s11883-018-0732-z. PMID 29728772. S2CID 21658334.
- Vaiserman A, Lushchak O (July 2017). "Implementation of longevity-promoting supplements and medications in public health practice: achievements, challenges and future perspectives". Journal of Translational Medicine. 15 (1): 160. doi:10.1186/s12967-017-1259-8. PMC 5520340. PMID 28728596.
- Shaposhnikov MV, Guvatova ZG, Zemskaya NV, Koval LA, Schegoleva EV, Gorbunova AA, et al. (June 2022). "Molecular mechanisms of exceptional lifespan increase of Drosophila melanogaster with different genotypes after combinations of pro-longevity interventions". Communications Biology. 5 (1): 566. doi:10.1038/s42003-022-03524-4. PMC 9184560. PMID 35681084.
- Stambler I (2014). A History of Life-Extensionism in the Twentieth Century. Longevity History. ISBN 978-1500818579.
- Hughes J (20 October 2011). "Transhumanism". In Bainbridge W (ed.). Leadership in Science and Technology: A Reference Handbook. SAGE Publications. p. 587. ISBN 978-1452266527.
- Zaleski A (12 June 2018). "Is there any truth to anti-aging schemes?". Popular Science.
- Schudel, Matt (6 December 1992). "Is it a crime to live forever?". SunSentinel.
- "William Faloon". lifeboatfoundation.
- West MD (2003). The Immortal Cell: One Scientist's Quest to Solve the Mystery of Human Aging. Doubleday. ISBN 978-0-385-50928-2.
- Stolyarov G (25 November 2013). Death is Wrong (PDF). Rational Argumentator Press. ISBN 978-0615932040.
- Istvan Z (2 October 2014). "The Morality of Artificial Intelligence and the Three Laws of Transhumanism". Huffington Post.
- "Futurist: 'I will reap benefits of life extension'". Al Jazeera America. 7 May 2015.
To Dvorsky, aging is a problem that's desperately in need of solving.
- Tez RM (11 May 2015). "Steve Aoki, Dan Bilzerian, a giraffe and the search for eternal life". i-D. VICE.
Unknown to most, Steve is both an undeniable champion of life expansion as well as one of the most prolific campaigners for life extension. Understanding that the depth of his life's experience is limited by time alone, in his latest album Neon Future he pens lyrics such as 'Life has limitless variety... But today, because of ageing, it does not have limitless scope.' [...] Set up by the Steve Aoki Charitable Fund, the profits from the Dan Bilzerian party went to life extension research.
- Kuczynski A (12 April 1998). "Anti-Aging Potion Or Poison?". The New York Times. Retrieved 17 July 2009.
- Jones T, Rae M, de Grey A. "Research Report 2011" (PDF). Sens Foundation. Archived from the original (PDF) on 14 August 2012.
- McNicoll A (3 October 2013). "How Google's Calico aims to fight aging and 'solve death'". CNN.
- "Google announces Calico, a new company focused on health and well-being". 18 September 2013.
- Human Longevity Inc. (4 March 2014). "Human Longevity Inc. (HLI) Launched to Promote Healthy Aging Using Advances in... – SAN DIEGO, March 4, 2014 /PRNewswire/ --". Archived from the original on 21 October 2014. Retrieved 12 August 2014.
- Landau, Elizabeth (5 May 2014). "Young blood makes old mice more youthful". CNN.
- Wood, Anthony (7 May 2014). "Harvard researchers find protein that could reverse the aging process". gizmag.com.
- Wolpert, Stuart (8 September 2014). "UCLA biologists delay the aging process by 'remote control'". UCLA Newsroom.
- "Australian and US scientists reverse ageing in mice, humans could be next". ABC News. 19 December 2013.
- Sobh R, Martin BA (2011). "Feedback Information and Consumer Motivation. The Moderating Role of Positive and Negative Reference Values in Self-Regulation" (PDF). European Journal of Marketing. 45 (6): 963–986. doi:10.1108/03090561111119976. Archived from the original (PDF) on 18 August 2014.
- "Scientists' Open Letter on Aging". Imminst.org. Retrieved 7 October 2012.
- "A Single-Issue Political Party for Longevity Science". Fightaging.org. 27 July 2012. Retrieved 7 October 2012.
- "Veritas Forum Q&A with Peter Thiel". YouTube.
- Friend T (3 April 2017). "Silicon Valley's Quest to Live Forever". The New Yorker.
- "Sam Altman invested $180 million into a company trying to delay death". MIT Technology Review. 8 March 2023.
- Smith S (3 December 2002). "Killing Immortality". Betterhumans. Archived from the original on 7 June 2004. Retrieved 17 July 2009.
- Kass L (1985). Toward a more natural science: biology and human affairs. New York City: Free Press. p. 316. ISBN 978-0-02-918340-3. OCLC 11677465.
- Harris J. (2007) Enhancing Evolution: The ethical case for making better people. Princeton University Press, New Jersey.
- Sutherland J (9 May 2006). "The ideas interview: Nick Bostrom". The Guardian. London. Retrieved 17 July 2009.
- Bostrom N (May 2005). "The fable of the dragon tyrant". Journal of Medical Ethics. 31 (5): 273–277. doi:10.1136/jme.2004.009035. PMC 1734155. PMID 15863685.
- "Superlongevity Without Overpopulation". Fight Aging!. 6 February 2005.
- "Peter Singer on Should We Live to 1,000? – Project Syndicate". Project Syndicate. 10 December 2012.
- "Living to 120 and Beyond: Americans' Views on Aging, Medical Advances and Radical Life Extension". Pew Research Center's Religion & Public Life Project. 6 August 2013.
- de Magalhães JP (October 2014). "The scientific quest for lasting youth: prospects for curing aging". Rejuvenation Research. 17 (5): 458–467. doi:10.1089/rej.2014.1580. PMC 4203147. PMID 25132068.
- Hayden EC (November 2007). "Age research: a new angle on 'old'". Nature. 450 (7170): 603–605. Bibcode:2007Natur.450..603H. doi:10.1038/450603a. PMID 18046373.
- Hamerman D. (2007) Geriatric Bioscience: The link between aging & disease. The Johns Hopkins University Press, Maryland.
- Moody HR (2002). "Who's afraid of life extension?". Generations. 25 (4): 33–7.
- Gems D (2011). "Aging: To Treat, or Not to Treat? The possibility of treating aging is not just an idle fantasy". American Scientist. 99 (4): 278–80. doi:10.1511/2011.91.278. S2CID 123698910.
- Gems D (January 2011). "Tragedy and delight: the ethics of decelerated ageing". Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences. 366 (1561): 108–112. doi:10.1098/rstb.2010.0288. PMC 3001315. PMID 21115537.
- Perlman RM (February 1954). "The aging syndrome". Journal of the American Geriatrics Society. 2 (2): 123–129. doi:10.1111/j.1532-5415.1954.tb00884.x. PMID 13129024. S2CID 45894370.
- Mehlman MJ, Binstock RH, Juengst ET, Ponsaran RS, Whitehouse PJ (June 2004). "Anti-aging medicine: can consumers be better protected?". The Gerontologist. 44 (3): 304–310. doi:10.1093/geront/44.3.304. PMID 15197284.
- Rando TA, Chang HY (January 2012). "Aging, rejuvenation, and epigenetic reprogramming: resetting the aging clock". Cell. 148 (1–2): 46–57. doi:10.1016/j.cell.2012.01.003. PMC 3336960. PMID 22265401.
- Johnson AA, Akman K, Calimport SR, Wuttke D, Stolzing A, de Magalhães JP (October 2012). "The role of DNA methylation in aging, rejuvenation, and age-related disease". Rejuvenation Research. 15 (5): 483–494. doi:10.1089/rej.2012.1324. PMC 3482848. PMID 23098078.
- Shmookler Reis RJ, Bharill P, Tazearslan C, Ayyadevara S (October 2009). "Extreme-longevity mutations orchestrate silencing of multiple signaling pathways". Biochimica et Biophysica Acta (BBA) - General Subjects. 1790 (10): 1075–1083. doi:10.1016/j.bbagen.2009.05.011. PMC 2885961. PMID 19465083.
- Childs BG, Durik M, Baker DJ, van Deursen JM (December 2015). "Cellular senescence in aging and age-related disease: from mechanisms to therapy". Nature Medicine. 21 (12): 1424–1435. doi:10.1038/nm.4000. PMC 4748967. PMID 26646499.
- Anderson RM, Shanmuganayagam D, Weindruch R (January 2009). "Caloric restriction and aging: studies in mice and monkeys". Toxicologic Pathology. 37 (1): 47–51. doi:10.1177/0192623308329476. PMC 3734859. PMID 19075044.
- Harrison DE, Strong R, Sharp ZD, Nelson JF, Astle CM, Flurkey K, et al. (July 2009). "Rapamycin fed late in life extends lifespan in genetically heterogeneous mice". Nature. 460 (7253): 392–395. Bibcode:2009Natur.460..392H. doi:10.1038/nature08221. PMC 2786175. PMID 19587680.
- Dhahbi JM, Mote PL, Fahy GM, Spindler SR (November 2005). "Identification of potential caloric restriction mimetics by microarray profiling". Physiological Genomics. 23 (3): 343–350. CiteSeerX 10.1.1.327.4892. doi:10.1152/physiolgenomics.00069.2005. PMID 16189280.
- Kaeberlein M (February 2010). "Resveratrol and rapamycin: are they anti-aging drugs?". BioEssays. 32 (2): 96–99. doi:10.1002/bies.200900171. PMID 20091754. S2CID 16882387.
- Barger JL, Kayo T, Vann JM, Arias EB, Wang J, Hacker TA, et al. (June 2008). "A low dose of dietary resveratrol partially mimics caloric restriction and retards aging parameters in mice". PLOS ONE. 3 (6): e2264. Bibcode:2008PLoSO...3.2264B. doi:10.1371/journal.pone.0002264. PMC 2386967. PMID 18523577.
- McCormack D, McFadden D (2013). "A review of pterostilbene antioxidant activity and disease modification". Oxidative Medicine and Cellular Longevity. 2013: 575482. doi:10.1155/2013/575482. PMC 3649683. PMID 23691264.
- Martel J, Ojcius DM, Wu CY, Peng HH, Voisin L, Perfettini JL, et al. (November 2020). "Emerging use of senolytics and senomorphics against aging and chronic diseases". Medicinal Research Reviews. 40 (6): 2114–2131. doi:10.1002/med.21702. PMID 32578904. S2CID 220047655.
- Mutlu AS, Duffy J, Wang MC (May 2021). "Lipid metabolism and lipid signals in aging and longevity". Developmental Cell. 56 (10): 1394–1407. doi:10.1016/j.devcel.2021.03.034. PMC 8173711. PMID 33891896.
- Shay KP, Moreau RF, Smith EJ, Smith AR, Hagen TM (October 2009). "Alpha-lipoic acid as a dietary supplement: molecular mechanisms and therapeutic potential". Biochimica et Biophysica Acta (BBA) - General Subjects. 1790 (10): 1149–1160. doi:10.1016/j.bbagen.2009.07.026. PMC 2756298. PMID 19664690.
- Arenas-Jal M, Suñé-Negre JM, García-Montoya E (March 2020). "Coenzyme Q10 supplementation: Efficacy, safety, and formulation challenges". Comprehensive Reviews in Food Science and Food Safety. 19 (2): 574–594. doi:10.1111/1541-4337.12539. PMID 33325173.
- Adamson SS, Brace LE, Kennedy BK (1 October 2017). "Alcohol and aging: From epidemiology to mechanism". Translational Medicine of Aging. 1: 18–23. doi:10.1016/j.tma.2017.09.001. ISSN 2468-5011.
- Ahmed A, Tollefsbol T (August 2001). "Telomeres and telomerase: basic science implications for aging". Journal of the American Geriatrics Society. 49 (8): 1105–1109. doi:10.1046/j.1532-5415.2001.49217.x. PMID 11555075. S2CID 2700393.
- Blackburn EH (September 2005). "Telomerase and Cancer: Kirk A. Landon--AACR prize for basic cancer research lecture". Molecular Cancer Research. 3 (9): 477–482. doi:10.1158/1541-7786.MCR-05-0147. PMID 16179494.
- Guterres, Adam N.; Villanueva, Jessie (September 2020). "Targeting telomerase for cancer therapy". Oncogene. 39 (36): 5811–5824. doi:10.1038/s41388-020-01405-w. ISSN 1476-5594. PMC 7678952. PMID 32733068.
- Kurzweil R (2005). The Singularity Is Near. New York City: Viking Press. ISBN 978-0-670-03384-3. OCLC 57201348.[page needed]
- Feynman RP (December 1959). "There's Plenty of Room at the Bottom". Archived from the original on 11 February 2010. Retrieved 22 March 2016.
- Melanson D (22 April 2008). "DoD establishes institute tasked with regrowing body parts". Engadget. Retrieved 29 June 2010.
- Khamsi R (4 April 2006). "Bio-engineered bladders successful in patients". New Scientist. Retrieved 26 January 2011.
- Lo, Bernard; Parham, Lindsay (1 May 2009). "Ethical Issues in Stem Cell Research". Endocrine Reviews. 30 (3): 204–213. doi:10.1210/er.2008-0031. PMC 2726839. PMID 19366754.
- White C (19 August 2005). "Umbilical stem cell breakthrough". The Australian. Archived from the original on 20 July 2009. Retrieved 17 July 2009.
- Segal D (1 June 2013). "This Man Is Not a Cyborg. Yet". The New York Times.
- McKie R (13 July 2002). "Cold facts about cryonics". The Observer. Retrieved 1 December 2013.
Cryonics, which began in the Sixties, is the freezing – usually in liquid nitrogen – of human beings who have been legally declared dead. The aim of this process is to keep such individuals in a state of refrigerated limbo so that it may become possible in the future to resuscitate them, cure them of the condition that killed them, and then restore them to functioning life in an era when medical science has triumphed over the activities of the Grim Reaper.
- Day E (10 October 2015). "Dying is the last thing anyone wants to do – so keep cool and carry on". The Guardian. Retrieved 21 February 2016.
- Butler K (1992). A Consumer's Guide to "Alternative" Medicine. Prometheus Books. p. 173.
- de Grey A, Rae M (2007). Ending Aging: The Rejuvenation Breakthroughs that Could Reverse Human Aging in Our Lifetime. New York City: St. Martin's Press. ISBN 978-0-312-36706-0. OCLC 132583222.[page needed]
- Pontin J (11 July 2006). "Is Defeating Aging Only A Dream?". Technology Review.
- Garreau J (31 October 2007). "The Invincible Man". Washington Post.
- Goya RG, Bolognani F, Hereñú CB, Rimoldi OJ (8 January 2001). "Neuroendocrinology of aging: the potential of gene therapy as an interventive strategy". Gerontology. 47 (3): 168–173. doi:10.1159/000052792. PMID 11340324. S2CID 10069927.
- Rattan SI, Singh R (January 2009). "Progress & prospects: gene therapy in aging". Gene Therapy. 16 (1): 3–9. doi:10.1038/gt.2008.166. PMID 19005494.
- Tacutu R, Craig T, Budovsky A, Wuttke D, Lehmann G, Taranukha D, et al. (January 2013). "Human Ageing Genomic Resources: integrated databases and tools for the biology and genetics of ageing". Nucleic Acids Research. 41 (Database issue): D1027–D1033. doi:10.1093/nar/gks1155. PMC 3531213. PMID 23193293.
- Timmers PR, Wilson JF, Joshi PK, Deelen J (July 2020). "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. 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) . The Selfish Gene. New York: Oxford University Press. pp. 41–42. ISBN 978-0-19-929115-1.
- Dawkins R (2006) . The Selfish Gene. New York: Oxford University Press. p. 42. ISBN 978-0-19-929115-1.
- Sandberg A, Boström 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?".
- Maxmen A (13 January 2017). "Questionable "Young Blood" Transfusions Offered in U.S. as Anti-Aging Remedy". MIT Technology Review. Retrieved 5 November 2017.
- 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.
- 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.
- Kosoff M (1 June 2017). "This anti-aging start-up is charging thousands of dollars for teen blood". Vanity Fair. Retrieved 5 November 2017.
- 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, Leñini 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.