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Ageing or aging (see spelling differences), is the process of becoming older. The term refers especially to human beings, many animals, and fungi, whereas for example bacteria, perennial plants and some simple animals are potentially immortal; in the broader sense, ageing can refer to single cells within an organism which have ceased dividing (cellular senescence) or to the population of a species (population ageing).




Ageing versus immortality

Immortal Hydra, a relative of the jellyfish

Human beings and members of other species, especially animals, necessarily experience ageing and mortality. Fungi, too, can age;[3] in contrast, many species can be considered immortal: for example, bacteria fission to produce daughter cells, strawberry plants grow runners to produce clones of themselves, and animals in the genus Hydra have a regenerative ability by which they avoid dying of old age.

Early life forms on Earth, starting at least 3.7 billion years ago,[4] were single-celled organisms. Such organisms (prokaryotes, protozoans, algae) multiply by fissioning into daughter cells; thus do not age and are innately immortal.[5][6]

Ageing and mortality of the individual organism became possible with the evolution of sexual reproduction,[7] which occurred with the emergence of the fungal/animal kingdoms approximately a billion years ago, and the evolution of flowering plants 160 million years ago. The sexual organism could henceforth pass on some of its genetic material to produce new individuals and could itself become disposable with respect to the survival of its species,[7] this classic biological idea has however been perturbed recently by the discovery that the bacterium E. coli may split into distinguishable daughter cells, which opens the theoretical possibility of "age classes" among bacteria.[8]

Even within humans and other mortal species, there are cells with the potential for immortality: cancer cells which have lost the ability to die when maintained in a cell culture such as the HeLa cell line,[9] and specific stem cells such as germ cells (producing ova and spermatozoa).[10] In artificial cloning, adult cells can be rejuvenated to embryonic status and then used to grow a new tissue or animal without ageing.[11] Normal human cells however die after about 50 cell divisions in laboratory culture (the Hayflick Limit, discovered by Leonard Hayflick in 1961).[9]

Effects of ageing



  • Teenagers lose the young child's ability to hear high-frequency sounds above 20 kHz.[13]
  • Cognitive decline begins in the mid-20s.[14][15]
  • Wrinkles develop mainly due to photoageing, particularly affecting sun-exposed areas (face).[16]
  • After peaking in the mid-20s, female fertility declines.[17]
  • People over 35 years of age are at risk for developing presbyopia.[18][19] and most people benefit from reading glasses by age 45–50.[20] The cause is lens hardening by decreasing levels of α-crystallin, a process which may be sped up by higher temperatures.[20][21]
  • Around age 50, hair turns grey.[22] Pattern hair loss by the age of 50 affects about half of males and a quarter of females.[23]
  • Almost half of people older than 75 have hearing loss inhibiting spoken communication.[26]
  • Frailty, defined as loss of muscle mass and mobility, affects 25% of those over 85.[28][29]
  • Atherosclerosis is classified as an ageing disease.[30] It leads to cardiovascular disease (for example stroke and heart attack)[31] which globally is the most common cause of death.[32]
  • The maximum human lifespan is suggested to be 115 years "for the foreseeable future".[33][34] The oldest reliably recorded human was Jeanne Calment who attained 122 years and died in 1997.

Dementia becomes more common with age.[35] About 3% of people between the ages of 65 and 74, 19% between 75 and 84, and nearly half of those over 85 years of age have dementia,[36] the spectrum ranges from mild cognitive impairment to the neurodegenerative diseases of Alzheimer's disease, cerebrovascular disease, Parkinson's disease and Lou Gehrig's disease. Furthermore, many types of memory may decline with ageing, but not semantic memory or general knowledge such as vocabulary definitions, which typically increases or remains steady until late adulthood[37] (see Ageing brain). Intelligence may decline with age, though the rate may vary depending on the type and may in fact remain steady throughout most of the lifespan, dropping suddenly only as people near the end of their lives. Individual variations in rate of cognitive decline may therefore be explained in terms of people having different lengths of life.[38] There might be changes to the brain: after 20 years of age there may be a 10% reduction each decade in the total length of the brain's myelinated axons.[39][40]

Age can result in visual impairment, whereby non-verbal communication is reduced,[41] which can lead to isolation and possible depression. Macular degeneration causes vision loss and increases with age, affecting nearly 12% of those above the age of 80.[42] This degeneration is caused by systemic changes in the circulation of waste products and by growth of abnormal vessels around the retina.[43]

A distinction can be made between "proximal ageing" (age-based effects that come about because of factors in the recent past) and "distal ageing" (age-based differences that can be traced to a cause in person's early life, such as childhood poliomyelitis).[38]

Ageing is among the greatest known risk factors for most human diseases.[2] Of the roughly 150,000 people who die each day across the globe, about two thirds—100,000 per day—die from age-related causes; in industrialised nations, the proportion is higher, reaching 90%.[44][45][46]

Biological basis


At present, researchers are only just beginning to understand the biological basis of ageing even in relatively simple and short-lived organisms such as yeast.[47] Less still is known of mammalian ageing, in part due to the much longer lives of even small mammals such as the mouse (around 3 years). A model organism for studying of ageing is the nematode C. elegans, thanks to its short lifespan of 2–3 weeks, our ability to easily perform genetic manipulations or to suppress gene activity with RNA interference, or other factors.[48] Most known mutations and RNA interference targets that extend lifespan were first discovered in C. elegans.[49]

The factors proposed to influence biological ageing[50] fall into two main categories, programmed and damage-related. Programmed factors follow a biological timetable, perhaps one that might be a continuation of the one that regulates childhood growth and development, this regulation would depend on changes in gene expression that affect the systems responsible for maintenance, repair and defence responses. Damage-related factors include internal and environmental assaults to living organisms that induce cumulative damage at various levels.[51]



Programmed factors


Clonal immortality apart, there are certain species whose individual lifespans stand out among Earth's life-forms, including the bristlecone pine at 5062 years[55] (however Hayflick states that the bristlecone pine has no cells older than 30 years), invertebrates like the hard clam (known as quahog in New England) at 508 years,[56] the Greenland shark at 400 years,[57] fish like the sturgeon and the rockfish, and the sea anemone[58] and lobster.[59][60] Such organisms are sometimes said to exhibit negligible senescence,[61] the genetic aspect has also been demonstrated in studies of human centenarians.


  • DNA methylation: The strong effect of age on DNA methylation levels has been known since the late 1960s.[63] Horvath hypothesised that DNA methylation age measures the cumulative effect of an epigenetic maintenance system but details are unknown. DNA methylation age of blood predicts all-cause mortality in later life.[64][65][66] Furthermore, prematurely aged mice can be rejuvenated and their lives extended by 30% by partially "resetting" the methylation pattern in their cells (a full reset leads to undesirable immortal cancer cells), this resetting into a juvenile state was experimentally achieved by activating the four Yamanaka DNA transcription factors – Sox2, Oct4, Klf4 and c-Myc (which have previously been routinely used for producing young animals from cloned adult skin cells).[67][68]
  • Telomeres: In humans and other animals, cellular senescence has been attributed to the shortening of telomeres at each cell division;[69] when telomeres become too short, the cells senesce and die or cease multiplying.[70] The length of telomeres is therefore the "molecular clock", predicted by Hayflick.[71][72] However, telomere length in wild mouse strains is unrelated to lifespan,[73] and mice lacking the telomerase enzyme do not have a dramatically reduced lifespan.[74] Laboratory mice's telomeres are many times longer than human ones.[75] Another caveat is that a study following nearly 1000 humans for ten years showed that while some humans do shorten their telomeres over time, a third of the participants did not.[76]
  • A variation in the gene FOXO3A has a positive effect on the life expectancy of humans, and is found much more often in people living to 100 and beyond – moreover, this appears to be true worldwide.[77][78] FOXO3A acts on the sirtuin family of genes which also have a significant effect on lifespan in yeast and in nematodes. Sirtuin in turn inhibits mTOR.[79]
  • Caloric restriction leads to longer lifespans in various species, an effect that is unclear,[53] but probably mediated by the nutrient-sensing function of the mTOR pathway.[80]
  • mTOR, a protein that inhibits autophagy, has been linked to ageing through the insulin signalling pathway. mTOR functions through nutrient and growth cues leading scientists to believe that dietary restriction and mTOR are related in terms of longevity. When organisms restrict their diet, mTOR activity is reduced, which allows an increased level of autophagy, this recycles old or damaged cell parts, which increases longevity and decreases the chances of being obese. This is thought to prevent spikes of glucose concentration in the blood, leading to reduced insulin signalling, this has been linked to less mTOR activation as well. Therefore, longevity has been connected to caloric restriction and insulin sensitivity inhibiting mTOR, which in turns allows autophagy to occur more frequently, it may be that mTOR inhibition and autophagy reduce the effects of reactive oxygen species on the body, which damage DNA and other organic material, so longevity would be increased.[81]
  • Over-expression of the Ras2 gene increases lifespan in yeast by 30%.[83] A yeast mutant lacking the genes sch9 and ras2 has recently been shown to have a tenfold increase in lifespan under conditions of calorie restriction and is the largest increase achieved in any organism.[84][85]
  • Evolutionary theories of ageing: Many have argued that life span, like other phenotypes, is selected. Traits that benefit early survival and reproduction will be selected for even if they contribute to an earlier death, such a genetic effect is called the antagonistic pleiotropy effect when referring to a gene (pleiotropy signifying the gene has a double function – enabling reproduction at a young age but costing the organism life expectancy in old age) and is called the disposable soma effect when referring to an entire genetic programme (the organism diverting limited resources from maintenance to reproduction).[7] The biological mechanisms which regulate lifespan evolved several hundred million years ago.[49]
    • Some evidence is provided by oxygen-deprived bacterial cultures.[86]
    • The theory would explain why the autosomal dominant disease, Huntington's disease, can persist even though it is inexorably lethal. Also, it has been suggested that some of the genetic variants that increase fertility in the young increase cancer risk in the old, such variants occur in genes p53[87] and BRCA1.[88]
An elderly Somali woman

Damage-related factors

  • Accumulation of waste:
    • A buildup of waste products in cells presumably interferes with metabolism. For example, a waste product called lipofuscin is formed by a complex reaction in cells that binds fat to proteins, this waste accumulates in the cells as small granules, which increase in size as a person ages.[96]
    • The hallmark of ageing yeast cells appears to be overproduction of certain proteins.[47]
  • Cross-linkage: The idea that ageing results from accumulation of cross-linked compounds that interfere with normal cell function.[72][100]
  • Studies of mtDNA mutator mice have shown that increased levels of somatic mtDNA mutations directly can cause a variety of ageing phenotypes. The authors propose that mtDNA mutations lead to respiratory-chain-deficient cells and thence to apoptosis and cell loss, they cast doubt experimentally however on the common assumption that mitochondrial mutations and dysfunction lead to increased generation of reactive oxygen species (ROS).[101]
  • Free-radical theory: Damage by free radicals, or more generally reactive oxygen species or oxidative stress, create damage that may gives rise to the symptoms we recognise as ageing.[72][102] Michael Ristow's group has provided evidence that the effect of calorie restriction may be due to increased formation of free radicals within the mitochondria, causing a secondary induction of increased antioxidant defence capacity.[103]
  • DNA oxidation and caloric restriction: Caloric restriction reduces 8-OH-dG DNA damage in organs of ageing rats and mice.[104][105] Thus, reduction of oxidative DNA damage is associated with a slower rate of ageing and increased lifespan.[106]

Prevention and delay


Caloric restriction substantially affects lifespan in many animals, including the ability to delay or prevent many age-related diseases.[107] Typically, this involves caloric intake of 60–70% of what an ad libitum animal would consume, while still maintaining proper nutrient intake;[107] in rodents, this has been shown to increase lifespan by up to 50%;[108] similar effects occur for yeast and Drosophila.[107] No lifespan data exist for humans on a calorie-restricted diet,[82] but several reports support protection from age-related diseases.[109][110] Two major ongoing studies on rhesus monkeys initially revealed disparate results; while one study, by the University of Wisconsin, showed that caloric restriction does extend lifespan,[111] the second study, by the National Institute on Ageing (NIA), found no effects of caloric restriction on longevity.[112] Both studies nevertheless showed improvement in a number of health parameters. Notwithstanding the similarly low calorie intake, the diet composition differed between the two studies (notably a high sucrose content in the Wisconsin study), and the monkeys have different origins (India, China), initially suggesting that genetics and dietary composition, not merely a decrease in calories, are factors in longevity.[82] However, in a comparative analysis in 2014, the Wisconsin researchers found that the allegedly non-starved NIA control monkeys in fact are moderately underweight when compared with other monkey populations, and argued this was due to the NIA's apportioned feeding protocol in contrast to Wisconsin's truly unrestricted ad libitum feeding protocol,[113] they conclude that moderate calorie restriction rather than extreme calorie restriction is sufficient to produce the observed health and longevity benefits in the studied rhesus monkeys.[114]


Alternatively, the benefits of dietary restriction can also be found by changing the macro nutrient profile to reduce protein intake without any changes to calorie level, resulting in similar increases in longevity.[117][118] Dietary protein restriction not only inhibits mTOR activity but also IGF-1, two mechanisms implicated in ageing.[80] Specifically, reducing leucine intake is sufficient to inhibit mTOR activity, achievable through reducing animal food consumption.[119][120]

The Mediterranean diet is credited with lowering the risk of heart disease and early death,[121][122] the major contributors to mortality risk reduction appear to be a higher consumption of vegetables, fish, fruits, nuts and monounsaturated fatty acids, i.e., olive oil.[123]

The amount of sleep has an impact on mortality. People who live the longest report sleeping for six to seven hours each night.[124][125] Lack of sleep (<5 hours) more than doubles the risk of death from cardiovascular disease, but too much sleep (>9 hours) is associated with a doubling of the risk of death, though not primarily from cardiovascular disease.[126] Sleeping more than 7 to 8 hours per day has been consistently associated with increased mortality, though the cause is probably other factors such as depression and socioeconomic status, which would correlate statistically.[127] Sleep monitoring of hunter-gatherer tribes from Africa and from South America has shown similar sleep patterns across continents: their average sleeping duration is 6.4 hours (with a summer/winter difference of 1 hour), afternoon naps (siestas) are uncommon, and insomnia is very rare (tenfold less than in industrial societies).[128]

Physical exercise may increase life expectancy.[129] People who participate in moderate to high levels of physical exercise have a lower mortality rate compared to individuals who are not physically active.[130] Moderate levels of exercise have been correlated with preventing aging and improving quality of life by reducing inflammatory potential,[131] the majority of the benefits from exercise are achieved with around 3500 metabolic equivalent (MET) minutes per week.[132] For example, climbing stairs 10 minutes, vacuuming 15 minutes, gardening 20 minutes, running 20 minutes, and walking or bicycling for 25 minutes on a daily basis would together achieve about 3000 MET minutes a week.[132]

Avoidance of chronic stress (as opposed to acute stress) is associated with a slower loss of telomeres in most but not all studies,[133][134] and with decreased cortisol levels. A chronically high cortisol level compromises the immune system, causes cardiac damage/arterosclerosis and is associated with facial ageing, and the latter in turn is a marker for increased morbidity and mortality.[135][136] Stress can be countered by social connection, spirituality, and (for men more clearly than for women) married life, all of which are associated with longevity.[137][138][139]

Medical intervention

The following drugs and interventions have been shown to retard or reverse the biological effects of ageing in animal models, but none has yet been proven to do so in humans.

Evidence in both animals and humans suggests that resveratrol may be a caloric restriction mimetic.[140]

As of 2015 metformin was under study for its potential effect on slowing ageing in the worm C.elegans and the cricket.[141] Its effect on otherwise healthy humans is unknown.[141]

Rapamycin was first shown to extend lifespan in eukaryotes in 2006 by Powers et al. who showed a dose-responsive effect of rapamycin on lifespan extension in yeast cells.[142] In a 2009 study, the lifespans of mice fed rapamycin were increased between 28 and 38% from the beginning of treatment, or 9 to 14% in total increased maximum lifespan. Of particular note, the treatment began in mice aged 20 months, the equivalent of 60 human years.[143] Rapamycin has subsequently been shown to extend mouse lifespan in several separate experiments,[144][145] and is now being tested for this purpose in nonhuman primates (the marmoset monkey).[146]

Cancer geneticist Ronald A. DePinho and his colleagues published research in mice where telomerase activity was first genetically removed. Then, after the mice had prematurely aged, they restored telomerase activity by reactivating the telomerase gene, as a result, the mice were rejuvenated: Shrivelled testes grew back to normal and the animals regained their fertility. Other organs, such as the spleen, liver, intestines and brain, recuperated from their degenerated state. "[The finding] offers the possibility that normal human ageing could be slowed by reawakening the enzyme in cells where it has stopped working" says Ronald DePinho. However, activating telomerase in humans could potentially encourage the growth of tumours.[147]


Research projects and prizes

Some research effort is directed to slow ageing and extend healthy lifespan.[148][149][150]


Several companies and organisations, such as Google Calico, Human Longevity, Craig Venter, Gero,[152] SENS Research Foundation, and Science for Life Extension in Russia,[153] declared stopping or delaying ageing as their goal.

Prizes for extending lifespan and slowing ageing in mammals exist, the Methuselah Foundation offers the Mprize. Recently, the $1 Million Palo Alto Longevity Prize was launched, it is a research incentive prize to encourage teams from all over the world to compete in an all-out effort to "hack the code" that regulates our health and lifespan. It was founded by Joon Yun.[154][155][156][157][158]

Society and culture

An elderly man

Different cultures express age in different ways, the age of an adult human is commonly measured in whole years since the day of birth. Arbitrary divisions set to mark periods of life may include: juvenile (via infancy, childhood, preadolescence, adolescence), early adulthood, middle adulthood, and late adulthood. More casual terms may include "teenagers," "tweens," "twentysomething", "thirtysomething", etc. as well as "denarian", "vicenarian", "tricenarian", "quadragenarian", etc.

Most legal systems define a specific age for when an individual is allowed or obliged to do particular activities, these age specifications include voting age, drinking age, age of consent, age of majority, age of criminal responsibility, marriageable age, age of candidacy, and mandatory retirement age. Admission to a movie for instance, may depend on age according to a motion picture rating system. A bus fare might be discounted for the young or old, each nation, government and non-governmental organisation has different ways of classifying age. In other words, chronological ageing may be distinguished from "social ageing" (cultural age-expectations of how people should act as they grow older) and "biological ageing" (an organism's physical state as it ages).[159]

In a UNFPA report about ageing in the 21st century, it highlighted the need to "Develop a new rights-based culture of ageing and a change of mindset and societal attitudes towards ageing and older persons, from welfare recipients to active, contributing members of society."[160] UNFPA said that this "requires, among others, working towards the development of international human rights instruments and their translation into national laws and regulations and affirmative measures that challenge age discrimination and recognise older people as autonomous subjects."[160] Older persons make contributions to society including caregiving and volunteering, for example, "A study of Bolivian migrants who [had] moved to Spain found that 69% left their children at home, usually with grandparents. In rural China, grandparents care for 38% of children aged under five whose parents have gone to work in cities."[160]


A map showing median age figures for 2015


In the 21st century, one of the most significant population trends is ageing.[162] Currently, over 11% of the world's current population are people aged 60 and older and the United Nations Population Fund (UNFPA) estimates that by 2050 that number will rise to approximately 22%.[160] Ageing has occurred due to development which has enabled better nutrition, sanitation, health care, education and economic well-being. Consequently, fertility rates have continued to decline and life expectancy have risen. Life expectancy at birth is over 80 now in 33 countries. Ageing is a "global phenomenon," that is occurring fastest in developing countries, including those with large youth populations, and poses social and economic challenges to the work which can be overcome with "the right set of policies to equip individuals, families and societies to address these challenges and to reap its benefits."[163]

As life expectancy rises and birth rates decline in developed countries, the median age rises accordingly. According to the United Nations, this process is taking place in nearly every country in the world.[164] A rising median age can have significant social and economic implications, as the workforce gets progressively older and the number of old workers and retirees grows relative to the number of young workers. Older people generally incur more health-related costs than do younger people in the workplace and can also cost more in worker's compensation and pension liabilities;[165] in most developed countries an older workforce is somewhat inevitable. In the United States for instance, the Bureau of Labor Statistics estimates that one in four American workers will be 55 or older by 2020.[165]


The global economic crisis has increased financial pressure to ensure economic security and access to health care in old age; in order to elevate this pressure "social protection floors must be implemented in order to guarantee income security and access to essential health and social services for all older persons and provide a safety net that contributes to the postponement of disability and prevention of impoverishment in old age."[160]


Due to increasing share of the elderly in the population, health care expenditures will continue to grow relative to the economy in coming decades, this has been considered as a negative phenomenon and effective strategies like labour productivity enhancement should be considered to deal with negative consequences of ageing.[167]


In the field of sociology and mental health, ageing is seen in five different views: ageing as maturity, ageing as decline, ageing as a life-cycle event, ageing as generation, and ageing as survival.[168] Positive correlates with ageing often include economics, employment, marriage, children, education, and sense of control, as well as many others, the social science of ageing includes disengagement theory, activity theory, selectivity theory, and continuity theory. Retirement, a common transition faced by the elderly, may have both positive and negative consequences.[169] As cyborgs currently are on the rise some theorists argue there is a need to develop new definitions of ageing and for instance a bio-techno-social definition of ageing has been suggested.[170]

Health care demand

With age inevitable biological changes occur that increase the risk of illness and disability. UNFPA states that,[163]


Many societies in Western Europe and Japan have ageing populations. While the effects on society are complex, there is a concern about the impact on health care demand, the large number of suggestions in the literature for specific interventions to cope with the expected increase in demand for long-term care in ageing societies can be organised under four headings: improve system performance; redesign service delivery; support informal caregivers; and shift demographic parameters.[171]

However, the annual growth in national health spending is not mainly due to increasing demand from ageing populations, but rather has been driven by rising incomes, costly new medical technology, a shortage of health care workers and informational asymmetries between providers and patients.[172] A number of health problems become more prevalent as people get older, these include mental health problems as well as physical health problems, especially dementia.


Self-perception of ageing

Positive self-perception of health has been correlated with higher well-being and reduced mortality in the elderly.[174][175] Various reasons have been proposed for this association; people who are objectively healthy may naturally rate their health better than that of their ill counterparts, though this link has been observed even in studies which have controlled for socioeconomic status, psychological functioning and health status.[176] This finding is generally stronger for men than women,[175] though this relationship is not universal across all studies and may only be true in some circumstances.[176]

As people age, subjective health remains relatively stable, even though objective health worsens;[177] in fact, perceived health improves with age when objective health is controlled in the equation.[178] This phenomenon is known as the "paradox of ageing." This may be a result of social comparison;[179] for instance, the older people get, the more they may consider themselves in better health than their same-aged peers.[180] Elderly people often associate their functional and physical decline with the normal ageing process.[181][182]

Successful ageing

The concept of successful ageing can be traced back to the 1950s and was popularised in the 1980s. Traditional definitions of successful ageing have emphasised absence of physical and cognitive disabilities;[183] in their 1987 article, Rowe and Kahn characterised successful ageing as involving three components: a) freedom from disease and disability, b) high cognitive and physical functioning, and c) social and productive engagement.[184]

Cultural references

The ancient Greek dramatist Euripides (5th century BC) describes the multiply-headed mythological monster Hydra as having a regenerative capacity which makes it immortal, which is the historical background to the name of the biological genus Hydra. The Book of Job (c. 6th century BC) describes human lifespan as inherently limited and makes a comparison with the innate immortality that a felled tree may have when undergoing vegetative regeneration.[185]

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