Ageing

From Wikipedia, the free encyclopedia This article is about human ageing. For other uses, see Ageing (disambiguation). This article is about all aspects of ageing. For the biological aspect of ageing specifically, see Senescence.

A human face showing signs of ageing Ageing (British English) or aging (American English) is the accumulation of changes in a person over time.[1] Ageing in humans refers to a multidimensional process of physical, psychological, and social change. Some dimensions of ageing grow and expand over time, while others decline. Reaction time, for example, may slow with age, while knowledge of world events and wisdom may expand. Research shows that even late in life, potential exists for physical, mental, and social growth and development.[2] Ageing is an important part of all human societies reflecting the biological changes that occur, but also reflecting cultural and societal conventions. Roughly 100,000 people worldwide die each day of age-related causes.[3] Age is measured chronologically, and a person's birthday is often an important event. However the term "ageing" is somewhat ambiguous. Distinctions may be made between "universal ageing" (age changes that all people share) and "probabilistic ageing" (age changes that may happen to some, but not all people as they grow older including diseases such as type two diabetes). Chronological ageing may also be distinguished from "social ageing" (cultural ageexpectations of how people should act as they grow older) and "biological ageing" (an organism's physical state as it ages).[citation needed] There is also a distinction 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 back to a cause early in person's life, such as childhood poliomyelitis).[4] Differences are sometimes made between populations of elderly people. Divisions are sometimes made between the young old (6574), the middle old (7584) and the oldest old (85+). However problematic this is, chronological age does not correlate perfectly with functional age, i.e. two people may be of the same age, but differ in their mental and physical capacities. Each nation, government and non-government organisation has different ways of classifying age. Population ageing is the increase in the number and proportion of older people in society. Population ageing has three possible causes: migration, longer life expectancy (decreased death rate), and decreased birth rate. Ageing has a significant impact on society. Young people tend to commit most crimes, they are more likely to push for political and social change, to develop and
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adopt new technologies, and to need education. Older people have different requirements from society and government as opposed to young people, and frequently differing values as well. Older people are also far more likely to vote, and in many countries the young are forbidden from voting. Thus, the aged have comparatively more political influence.[citation needed] Recent scientific successes in rejuvenation and extending a lifespan of model animals (mice 2.5 times, yeast and nematodes 10 times) and discovery of variety of species (including humans of advanced ages)[5][not in citation given] having negligible senescence give hope to achieve negligible senescence (cancel ageing) for younger humans, reverse ageing or at least significantly delay it. In spite of the developments mentioned above and the fact that ageing is admitted to be the major cause of mortality in developed worlds,[6][7] scientists consider anti-ageing and life extension research to be greatly underfunded.[8] Although human life is declared to be a basic value in many societies, there is no strong awareness and thus demand for society to cancel human ageing. The body still technically ages after death as it still gets older from birth.[9] Early observations The first formal studies of ageing appear to be those of Muhammad ibn Yusuf al-Harawi (1582) in his book Ainul Hayat, published by Ibn Sina Academy of Medieval Medicine and Sciences.[10] This book is based only on ageing and its related issues. The original manuscript of Ainul Hayat was scribed in 1532 by the author Muhammad ibn Yusuf al-Harawi. Four copies of the manuscript survive and were reprinted in an edited and translated version by Hakim Syed Zillur Rahman (2007). The book discusses behavioural and lifestyle factors putatively influencing ageing including diet, environment and housing conditions. Also discussed are drugs that may increase and decrease ageing rates. Senescence Main article: Senescence

A map showing median age figures for 2001 In biology, senescence is the state or process of ageing. Cellular senescence is a phenomenon where isolated cells demonstrate a limited ability to divide in culture (the Hayflick Limit, discovered by Leonard Hayflick in 1961), while organismal senescence is the ageing of organisms. After a period of near perfect renewal (in humans, between 20 and 35 years of age), organismal senescence is characterised by the declining ability to respond to stress, increasing homeostatic imbalance and increased risk of disease. This currently irreversible series of changes inevitably ends in death. Some researchers (specifically biogerontologists) are treating ageing as

a disease. As genes that have an effect on ageing are discovered, ageing is increasingly being regarded in a similar fashion to other geneticly influenced "conditions", potentially "treatable". Some claim aging is an avoidable property of life, that it is the result of a genetic program. Numerous species show very low signs of aging ("negligible senescence"), the best known being trees like the bristlecone pine (however Hayflick states that the bristlecone pine has no cells older than 30 years), fish like the sturgeon and the rockfish, invertebrates like the quahog and sea anemone[11] and lobster.[12][13] In humans and other animals, cellular senescence has been attributed to the shortening of telomeres with each cell cycle; when telomeres become too short, the cells die. The length of telomeres is therefore the "molecular clock", predicted by Hayflick. The quantity of the Hematopoietic stem cells that produce the blood components residing in the bone marrow of human beings have been found to decline with ageing.[14] Among the signs of senescence subjective vertigo is reported.[15] Telomere length is maintained in immortal cells (e.g. germ cells and keratinocyte stem cells, but not other skin cell types) by the telomerase enzyme. In the laboratory, mortal cell lines can be immortalised by the activation of their telomerase gene, present in all cells but active in few cell types. Cancerous cells must become immortal to multiply without limit. This important step towards carcinogenesis implies, in 85% of cancers, the reactivation of their telomerase gene by mutation. Since this mutation is rare, the telomere "clock" is seen by some as a protective mechanism against cancer.[16] Research has shown that the clock must be located in the nucleus of each cell and there have been reports that the longevity clock might be located in genes on either the first or fourth chromosome of the twenty-three pairs of human chromosomes. Other genes are known to affect the ageing process. The sirtuin family of genes have been shown to have a significant effect on the lifespan of yeast and nematodes. Over-expression of the RAS2 gene increases lifespan in yeast substantially. In addition to genetic ties to lifespan, diet has been shown to substantially affect lifespan in many animals. Specifically, caloric restriction (that is, restricting calories to 3050% less than an ad libitum animal would consume, while still maintaining proper nutrient intake), has been shown to increase lifespan in mice up to 50%.[citation needed] Caloric restriction works on many other species beyond mice (including species as diverse as yeast and Drosophila), and appears (though the data is not conclusive) to increase lifespan in primates according to a study done on Rhesus monkeys at the National Institute of Health (US), although the increase in lifespan is only notable if the caloric restriction is started early in life.[citation needed] Since, at the molecular level, age is counted not as time but as the number of cell doublings, this effect of calorie reduction could be mediated by the slowing of cellular growth and, therefore, the lengthening of the time between cell divisions.[dubious discuss][citation needed] Drug companies are currently searching for ways to mimic the lifespan-extending effects of caloric restriction without having to severely reduce food consumption.[weasel words][citation needed]

In his book, How and Why We Age, Hayflick notes a contradiction to the caloric restriction longevity increase theory for humans, noting that data from the Baltimore Longitudinal Study of Aging show that being thin does not favour longevity.[need quotation to verify][citation needed] Of the roughly 150,000 people who die each day across the globe, about two thirds100,000 per daydie of age-related causes.[3] In industrialized nations, the proportion is much higher, reaching 90%.[3] The evolution of ageing Because evolution is the unifying theory of biology, understanding how evolution works is essential for explaining why we age. Ageing evolves because of the interaction of two effects. First, natural selection is stronger on the young than on the old; this explains why the autosomal dominant disease, Huntington's Disease, can persist even though it is inexorably lethal. Second, any genetic, developmental, or physiological effect that increases the reproductive performance of the young will evolve so long as the costs that it imposes on the old are not too great.[17] Or put another way, traits that benefit early survival and reproduction will be selected for even if they contribute to an earlier death. Such genetic effects are called antagonistic pleiotropy. "Antagonistic" refers to the impact on fitness in the young, which is positive, and the negative effect on the old. Genetic pleiotropy refers to genes that have multiple effects. Antagonistic pleiotropy has been identified both in model organisms and in humans.[18] In humans, some of the genetic variants that increase fertility in the young are now known to increase cancer risk in the old. Such genes include p53[19] and BRCA1.[20] Dividing the lifespan

An elderly woman. An animal's life is often divided into various age ranges. However, because biological changes are slow-moving and can vary within one's own species, arbitrary dates are usually set to mark periods of life. The human divisions given below are not valid in all cultures:

Juvenile [via infancy, childhood, preadolescence, adolescence (teenager)]: 019 Early adulthood: 2039 Middle adulthood: 4059 Late adulthood: 60+

Ages can also be divided into numerical units:

Term Age (years, inclusive) Denarian 10 to 19 Vicenarian 20 to 29 Tricenarian 30 to 39 Quadragenarian 40 to 49 Quinquagenarian 50 to 59 Sexagenarian 60 to 69 Septuagenarian 70 to 79 Octogenarian 80 to 89 Nonagenarian 90 to 99 Centenarian 100 to 109 Supercentenarian 110 and older

People from 13 to 19 years of age are also known as teens or teenagers. Tween or Twelvie is an American neologism referring to someone aged 10 through 12.[21] The casual terms "twentysomething", "thirtysomething", etc. are also in use to describe people by decades of age. Cultural variations In some cultures there are other ways to express age: by counting years with or without including current year. For example, it could be said about the same person that he is twenty years old or that he is in the twenty-first year of his life. In Russian the former expression is generally used, the latter one has restricted usage: it is used for age of a deceased person in obituaries and for the age of an adult when it is desired to show him/her older than he/she is. (Psychologically, a woman in her 20th year seems older than one who is 19 years old.) Depending on cultural and personal philosophy, ageing can be seen as an undesirable phenomenon, reducing beauty and bringing one closer to death; or as an accumulation of wisdom, mark of survival, and a status worthy of respect. In some cases numerical age is important (whether good or bad), whereas others find the stage in life that one has reached (adulthood, independence, marriage, retirement, career success) to be more important. East Asian age reckoning is different from that found in Western culture. Traditional Chinese culture uses a different ageing method, called Xusui () with respect to common ageing which is called Zhousui (). In the Xusui method, people are born at age 1, not age 0, possibly because conception is already considered to be the start of the life span and possibly because the number '0' was not historically present in Ancient China,[citation needed] and another difference is the ageing day: Xusui grows up at the Spring Festival (aka. Chinese New Year's Day), while Zhousui grows up at one's birthday. Society

Legal

An elderly man. There are variations in many countries as to what age a person legally becomes an adult. Most legal systems define a specific ages for when an individual is allowed or obliged to do particular activities. These ages 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. Similarly in many countries in jurisprudence, the defence of infancy is a form of defence by which a defendant argues that, at the time a law was broken, they were not liable for their actions, and thus should not be held liable for a crime. Many courts recognise that defendants who are considered to be juveniles may avoid criminal prosecution on account of their age, and in borderline cases the age of the offender is often held to be a mitigating circumstance.

Economics
See also: Population ageing As life expectancy rises and birth rates decline in developed countries, the median age itself rises. According to the United Nations, this process is taking place in nearly every country in the world.[22] 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, and in the workplace can also cost more in worker's compensation and pension liabilities.[23] 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.[23]

Health care demand

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.[24]

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.[25] 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. (Main article: Dementia]. Even so, it has been estimated that population ageing only explains 0.2 percentage points of the annual growth rate in medical spending of 4.3 percent since 1970. In addition, certain reforms to Medicare decreased elderly spending on home health care by 12.5 percent per year between 1996 and 2000.[26] This would suggest that the impact of ageing populations on health care costs is not inevitable.

Impact on prisons
As of July 2007, medical costs for a typical inmate in the United States might run an agency around $33 per day, while costs for an ageing inmate could run upwards of $100. Most State DOCs report spending more than 10 percent of the annual budget on elderly care. That is expected to rise over the next 1020 years. Some states have talked about releasing ageing inmates early.[27] Cognitive effects Steady decline in many cognitive processes is seen across the lifespan, accelerating from the twenties or thirties.[28] Research has focused in particular on memory and ageing, and has found decline in many types of memory with ageing, but not in semantic memory or general knowledge such as vocabulary definitions, which typically increases or remains steady until the late adulthood.[29] Early studies on changes in cognition with age generally found declines in intelligence in the elderly, but studies were cross-sectional rather than longitudinal and thus results may be an artefact of cohort rather than a true example of decline. However, longitudinal studies could be confounded due to prior test experience.[30] 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.[4] There are changes to the brain: though neuron loss is minor after 20 years of age there is a 10% reduction each decade in the total length of the brain's myelinated axons.[31] Coping and well-being

Elderly Gambian woman.

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Psychologists have examined coping skills in the elderly. Various factors, such as social support, religion and spirituality, active engagement with life and having an internal locus of control have been proposed as being beneficial in helping people to cope with stressful life events in later life.[32][33][34] Social support and personal control are possibly the two most important factors that predict well-being, morbidity and mortality in adults.[35] Other factors that may link to well-being and quality of life in the elderly include social relationships (possibly relationships with pets as well as humans), and health.[36] Individuals in different wings in the same retirement home have demonstrated a lower risk of mortality and higher alertness and self-rated health in the wing where residents had greater control over their environment,[37][38] though personal control may have less impact on specific measures of health.[34] Social control, perceptions of how much influence one has over one's social relationships, shows support as a moderator variable for the relationship between social support and perceived health in the elderly, and may positively influence coping in the elderly.[39]

Religion
Religion has been an important factor used by the elderly in coping with the demands of later life, and appears more often than other forms of coping later in life.[40] Religiosity is a multidimensional variable; while participation in religious activities in the sense of participation in formal and organised rituals may decline, it may become a more informal, but still important aspect of life such as through personal or private prayer.[41]

Self-rated health
Self-ratings of health, the beliefs in one's own health as excellent, fair or poor, has been correlated with well-being and mortality in the elderly; positive ratings are linked to high wellbeing and reduced mortality.[42][43] 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.[44] This finding is generally stronger for men than women,[43] though the pattern between genders is not universal across all studies, and some results suggest sex-based differences only appear in certain age groups, for certain causes of mortality and within a specific sub-set of self-ratings of health.[44]

Retirement
Retirement, a common transition faced by the elderly, may have both positive and negative consequences.[45] Successful ageing Main article: Successful ageing

Two men practicing Tahtib, one of them lost his hair, indicating advanced age active Ageing, on an Ostraca from Ancient Egypt, Louvre The concept of successful ageing can be traced back to the 1950s, and was popularised in the 1980s. Previous research into ageing exaggerated the extent to which health disabilities, such as diabetes or osteoporosis, could be attributed exclusively to age, and research in gerontology exaggerated the homogeneity of samples of elderly people.[46][47] Successful ageing consists of three components:[48] 1. Low probability of disease or disability; 2. High cognitive and physical function capacity; 3. Active engagement with life. A greater number of people self-report successful ageing than those that strictly meet these criteria.[46] Successful ageing may be viewed an interdisciplinary concept, spanning both psychology and sociology, where it is seen as the transaction between society and individuals across the life span with specific focus on the later years of life.[49] The terms "healthy ageing"[46] and "optimal ageing" have been proposed as alternatives to successful ageing, partly because the term "successful ageing" has been criticised for making healthy ageing sound too competitive. Six suggested dimensions of successful ageing include:[34] 1. 2. 3. 4. 5. 6. No physical disability over the age of 75 as rated by a physician; Good subjective health assessment (i.e. good self-ratings of one's health); Length of undisabled life; Good mental health; Objective social support; Self-rated life satisfaction in eight domains, namely marriage, income-related work, children, friendship and social contacts, hobbies, community service activities, religion and recreation/sports.

Political struggle against ageing Though a lot of scientists state that radical life extension, delaying and stopping ageing are achievable,[50] there are still no international or national programmes focused on stopping ageing or on radical life extension. There are political forces staying for and against life extension. In
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2012 in Russia, and then in USA, Israel and Netherlands the Longevity political parties started. These parties aim to provide political support to anti-ageing and radical life extension research and technologies and want to ensure fastest possible and at the same time soft societal transition to the next step: radical life extension and life without ageing, that will make it possible to provide the access to such technologies to the most of the currently living people.[51]

Theories
Biological theories

95-year-old woman holding a five-month-old boy At present, the biological basis of ageing is unknown. Most scientists agree that substantial variability exists in the rates of ageing across different species, and that this to a large extent is genetically based. In model organisms and laboratory settings, researchers have been able to demonstrate that selected alterations in specific genes can extend lifespan (quite substantially in nematodes, less so in fruit flies, and less again in mice. Life span extension can occur as the result of genetic alterations that increase DNA repair, reduce oxidative damage or reduce cell suicide (apoptosis) due to DNA damage.[52] Even in the relatively simple and short-lived organisms, the mechanism of ageing remain to be elucidated. Less is known about mammalian ageing, in part due to the much longer lives in even small mammals such as the mouse (around 3 years). The US National Institute on Aging currently funds an intervention testing program, whereby investigators nominate compounds (based on specific molecular ageing theories) to have evaluated with respect to their effects on lifespan and age-related biomarkers in outbred mice.[53] Previous age-related testing in mammals has proved largely irreproducible, because of small numbers of animals, and lax mouse husbandry conditions. The intervention testing program aims to address this by conducting parallel experiments at three internationally recognised mouse ageing-centres, the Barshop Institute at UTHSCSA, the University of Michigan at Ann Arbor and the Jackson Laboratory. Many have argued that life-span, like other phenotypes, is selected.

Evolutionary Theories: Enquiry into the evolution of ageing aims to explain why almost all living things weaken and die with age. Exceptions such as rockfish, turtles, and naked molerat are highly informative.[citation needed]

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Telomere Theory: Telomeres (structures at the ends of chromosomes) have experimentally been shown to shorten with each successive cell division.[54] Shortened telomeres activate a mechanism that prevents further cell multiplication[citation needed]. This may be particularly limit in tissues such as bone marrow and the arterial lining where cell division occurs repeatedly throughout life.[55] Importantly though, mice lacking telomerase enzyme do not show a dramatically reduced lifespan,[56] invalidating at least simple versions of the telomere theory of ageing. Mice may be an exception for the theory, as they have long hypervariable telomeres,[57] prolonging the period after which telomere shortening would affect life-span. But wild mouse strains do not, and telomere length in these breeds is unrelated to lifespan[58] Reproductive-Cell Cycle Theory: The idea that ageing is regulated by reproductive hormones that act in an antagonistic pleiotropic manner via cell cycle signaling, promoting growth and development early in life in order to achieve reproduction, but later in life, in a futile attempt to maintain reproduction, become dysregulated and drive senescence (dyosis).[1][59]

Some theories suggest that ageing is a disease. Two examples are

DNA damage theory of aging (Main article): Known causes of cancer (radiation, chemical and viral) account for about 30% of the total cancer burden and for about 30% of the total DNA damage. DNA damage causes the cells to stop dividing or induce apoptosis, often affecting stem cell pools and hence hindering regeneration. DNA damage is thought to be the common pathway causing both cancer and ageing. Viral infection would appear to be the most likely cause of the other 70% of DNA damage especially in cells that are not exposed to smoking and sun light. It has been argued, too, that intrinsic causes of DNA damage are more important drivers of ageing.[60][61] Autoimmune Theory: The idea that ageing results from an increase in autoantibodies that attack the body's tissues. A number of diseases associated with ageing, such as atrophic gastritis and Hashimoto's thyroiditis, are probably autoimmune in this way. While inflammation is very much evident in old mammals, even SCID mice in SPF colonies still experience senescence.

Genetic theories

An elderly Somali woman. Many theories suggest that ageing results from the accumulation of damage to DNA in the cell, or organ. Since DNA is the formative basis of cell structure and function, damage to the DNA molecule, or genes, can lead to its loss of integrity and early cell death.

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Examples include:

Accumulative-Waste Theory: The biological theory of ageing that points to a buildup of cells of waste products that presumably interferes with metabolism. Wear-and-Tear Theory: The very general idea that changes associated with ageing are the result of chance damage that accumulates over time. Somatic Mutation Theory: The biological theory that ageing results from damage to the genetic integrity of the bodys cells. Error Accumulation Theory: The idea that ageing results from chance events that escape proof reading mechanisms, which gradually damages the genetic code.

Some have argued that ageing is programmed: that an internal clock detects a time to end investing in the organism, leading to death. This ageing-Clock Theory suggests, as in a clock, an ageing sequence is built into the operation of the nervous or endocrine system of the body. In rapidly dividing cells the shortening of the telomeres would provide such a clock. This idea is in contradiction with the evolutionary based theory of ageing.[62][63]

Cross-Linkage Theory: The idea that ageing results from accumulation of cross-linked compounds that interfere with normal cell function.[63][64] Free-Radical Theory: The idea that free radicals (unstable and highly reactive organic molecules), or more generally reactive oxygen species or oxidative stress create damage that gives rise to symptoms we recognize as ageing.[63][65] Reliability theory of ageing and longevity: A general theory about systems failure. It allows researchers to predict the age-related failure kinetics for a system of given architecture (reliability structure) and given reliability of its components. Reliability theory predicts that even those systems that are entirely composed of non-ageing elements (with a constant failure rate) will nevertheless deteriorate (fail more often) with age, if these systems are redundant in irreplaceable elements. Ageing, therefore, is a direct consequence of systems redundancy. Reliability theory also predicts the late-life mortality deceleration with subsequent levelling-off, as well as the late-life mortality plateaus, as an inevitable consequence of redundancy exhaustion at extreme old ages. The theory explains why mortality rates increase exponentially with age (the Gompertz law) in many species, by taking into account the initial flaws (defects) in newly formed systems. It also explains why organisms "prefer" to die according to the Gompertz law, while technical devices usually fail according to the Weibull (power) law. Reliability theory allows to specify conditions when organisms die according to the Weibull distribution: organisms should be relatively free of initial flaws and defects. The theory makes it possible to find a general failure law applicable to all adult and extreme old ages, where the Gompertz and the Weibull laws are just special cases of this more general failure law. The theory explains why relative differences in mortality rates of compared populations (within a given species) vanish with age (compensation law of mortality), and mortality convergence is observed due to the exhaustion of initial differences in redundancy levels. Mitohormesis: It has been known since the 1930s that restricting calories while maintaining adequate amounts of other nutrients can extend lifespan in laboratory animals. Recently, Michael Ristow's group has provided evidence for the theory that this

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effect is due to increased formation of free radicals within the mitochondria causing a secondary induction of increased antioxidant defence capacity.[66] Misrepair-Accumulation Theory: Wang et al.[67] suggest that ageing is the result of the accumulation of "Misrepair". Important in this theory is to distinguish among "damage" which means a newly emerging defect BEFORE any reparation has taken place, and "Misrepair" which describes the remaining defective structure AFTER (incorrect) repair. The key points in this theory are:

1. There is no original damage left unrepaired in a living being. If damage was left unrepaired a life threatening condition (such as bleeding, infection, or organ failure) would develop. 2. Misrepair, the repair with less accuracy, does not happen accidentally. It is a necessary measure of the reparation system to achieve sufficiently quick reparation in situations of serious or repeated damage, to maintain the integrity and basic function of a structure, which is important for the survival of the living being. 3. Hence the appearance of Misrepair increases the chance for the survival of individual, by which the individual can live at least up to the reproduction age, which is critically important for the survival of species. Therefore the Misrepair mechanism was selected by nature due to its evolutionary advantage. 4. However, since Misrepair as a defective structure is invisible for the reparation system, it accumulates with time and causes gradually the disorganisation of a structure (tissue, cell, or molecule); this is the actual source of ageing. 5. Ageing hence is the side-effect for survival, but important for species survival. Thus Misrepair might represent the mechanism by which organisms are not programmed to die but to survive (as long as possible), and ageing is just the price to be paid.

Non-biological theories

An elderly Iraqi man. Disengagement Theory This is the idea that separation of older people from active roles in society is normal and appropriate, and benefits both society and older individuals. Disengagement theory, first proposed by Cumming and Henry, has received considerable attention in gerontology, but has been much criticised.[4] The original data on which Cumming and Henry based the theory were from a rather small sample of older adults in Kansas City, and from this select sample Cumming and Henry then took disengagement to be a universal theory.[68] There are research data suggesting that the elderly who do become detached from society are those who were initially reclusive individuals, and such disengagement is not purely a response to ageing.[4] Activity theory
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In contrast to disengagement theory, this theory implies that the more active elderly people are, the more likely they are to be satisfied with life. The view that elderly adults should maintain well-being by keeping active has had a considerable history, and since 1972, this has come to be known as activity theory.[68] However, this theory may be just as inappropriate as disengagement for some people as the current paradigm on the psychology of ageing is that both disengagement theory and activity theory may be optimal for certain people in old age, depending on both circumstances and personality traits of the individual concerned.[4] There are also data which query whether, as activity theory implies, greater social activity is linked with well-being in adulthood.[68] Selectivity Theory This theory mediates between Activity and Disengagement Theory, which suggests that it may benefit older people to become more active in some aspects of their lives, more disengaged in others.[68] Continuity Theory The view that in ageing people are inclined to maintain, as much as they can, the same habits, personalities, and styles of life that they have developed in earlier years. Continuity theory is Atchley's theory that individuals, in later life, make adaptations to enable them to gain a sense of continuity between the past and the present, and the theory implies that this sense of continuity helps to contribute to well-being in later life.[36] Disengagement theory, activity theory and continuity theory are social theories about ageing, though all may be products of their era rather than a valid, universal theory. Prevention and reversal

Old man at a nursing home in Norway. See also: Life extension Several drugs and food supplements have been shown to retard or reverse the biological effects of ageing in animal models; none has yet been proven to do so in humans. Resveratrol, a chemical found in red grapes, has been shown to extend the lifespan of yeast by 60%, worms and flies by 30% and one species of fish by almost 60%. It does not extend the lifespan of healthy mice but delays the onset of age-related disease and infirmity.[69] Transcendental Meditation (TM technique) may have beneficial age-related effects.[70]
[71][72][73][74]

Small doses of heavy water increase fruit-fly lifespan by 30%, but large doses are toxic to complex organisms.
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In 2002, a team led by Professor Bruce Ames at UC Berkeley discovered that feeding aged rats a combination of acetyl-L-carnitine and alpha-lipoic acid (both substances are already approved for human use and sold in health food stores) produced a rejuvenating effect.[75] Ames said, "With these two supplements together, these old rats got up and did the macarena. The brain looks better, they are full of energy everything we looked at looks like a young animal." UC Berkeley has patented the use of these supplements in combination and a company, Juvenon, has been established to market the treatment. In 2007, researchers at the Salk Institute for Biological Studies identified a critical gene in nematode worms that specifically links eating fewer calories with living longer. Professor Andrew Dillin and colleagues showed that the gene pha-4 regulates the longevity response to calorie restriction.[76] In the same year Dr Howard Chang of the Stanford University School of Medicine was able to rejuvenate the skin of two-year-old mice to resemble that of newborns by blocking the activity of the gene NF-kappa-B.[77] In 2008, a team at the Spanish National Cancer Research Center genetically engineered mice to produce ten times the normal level of the telomerase enzyme.[78] The mice lived 26% longer than normal.[79] Also in 2008, a team led by Professor Michael O Thorner at the University of Virginia discovered that the drug MK-677 restored 20% of muscle mass lost due to ageing in humans aged 60 to 81. The subjects' growth hormone and insulin-like growth factor 1 (IGF-1) levels increased to that typical of healthy young adults.[80] In 2009, a drug called rapamycin, discovered in the 1970s in the soil of Easter Island in the South Pacific, was found to extend the life expectancy of 20-month-old mice by up to 38%.[81] Rapamycin is approved for human use and is generally used to suppress the immune system and prevent the rejection of transplanted organs. It is thought to mimic the effect of calorie restriction.[82] Dr Arlan Richardson of the Barshop Institute said, "I never thought we would find an anti-ageing pill in my lifetime; however, rapamycin shows a great deal of promise to do just that." Professor Randy Strong of the University of Texas Health Science Center at San Antonio said, "We believe this is the first convincing evidence that the ageing process can be slowed and lifespan can be extended by a drug therapy starting at an advanced age."

Sign outside a modern anti-ageing clinic in Germany.

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Also in 2009, the British Journal of Nutrition reported a study at Tufts University in Boston which showed that brain function and motor skills in aged rats could be improved by adding walnuts to their diet. The human equivalent would be to eat seven to nine walnuts per day.[83] In September 2009, researchers at UC Berkeley discovered they could restore youthful repair capability to muscle tissue taken from men aged 68 to 74 by in vitro treatment with mitogenactivated protein kinase.[84] This protein was found to be essential for the production of the stem cells necessary to repair muscle after exercise and is present at reduced levels in aged individuals. Ronald A. DePinho, a cancer geneticist at the Dana-Farber Cancer Institute and Harvard Medical School, published a paper[85] in Nature magazine in November 2010 which indicated that the organs of genetically altered mice, designed to activate telomerase after feeding them with a chemical, 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. Dr Lynne Cox of Oxford University said, "This paper is extremely important as it provides proof of the principle that short-term treatment to restore telomerase in adults already showing age-related tissue degeneration can rejuvenate aged tissues and restore physiological function." In this experiment mice were engineered to not produce telomerase naturally but after a chemical "switch" the system would then restore telomerase. Importantly, this chemical does not have the ability to produce telomerase in animals that are not genetically altered. Moreover, telomerase activation is also associated with the growth of cancerous tumours which could prevent antiageing treatments using this discovery. Measure of age The age of an adult human is commonly measured in whole years since the day of birth. Fractional years, months or even weeks may be used to describe the age of children and infants for finer resolution. The time of day the birth occurred is not commonly considered. The measure of age has historically varied from this approach in some cultures. In parts of Tibet, age is counted from conception i.e. one is usually 9 months old when one is born.[86] Age in prenatal development is normally measured in gestational age, taking the last menstruation of the mother as a point of beginning. Alternatively, fertilisation age, beginning from fertilisation can be taken. Obtaining survey data on ageing Numerous worldwide health, ageing and retirement surveys contain questions pertaining to pensions. The Meta Data Repository created by the non-profit RAND Corporation and sponsored by the National Institute on Aging at the National Institutes of Health provides

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access to meta data for these questions as well as links to obtain respondent data from the originating surveys.

SIGNS & SYMPTOMS OF AGING

There are many different signs and symptoms of aging. Most of these develop gradually and are very diverse, but it should be remembered that it is not possible to diagnose aging based on isolated signs and symptoms alone. Different people possess widely varying degrees of these signs and symptoms. Some of these include:

An overall decrease in energy and vigor The tendency to become easily tired Changes in sleeping patterns Decreased memory Behavioural changes Skin and hair changes such as wrinkles, brown spots on the skin, loss of skin elasticity, and hair loss affecting the limbs Changes in hair colour A loss or decrease in vision and hearing Changes in bowel function Decrease in libido Sexual dysfunction Urinary problems such as incontinence, dribbling, and changes in frequency of urination Changes in menstrual cycle Abdominal obesity and inability to lose weight

Sooner or later, many people develop one or more of the degenerative diseases of aging, such as:

Alzheimer's disease Stroke Heart attack Cancer Osteoporosis Diabetes Mellitus Parkinson's disease Arthritis Cataracts Glaucoma Hearing loss

These conditions cause pain and suffering to patients and their families - the economic and social costs are staggering. Psychologists who work with older adults known as geropsychologists assess mental functioning, depression and other problems and provide psychotherapy. They also help design policies and services to enhance the quality of life of older people and their caregivers.
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