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A human face showing signs of ageing
Ageing (British English) or aging (American English) is the process of becoming older. It represents the accumulation of changes in a person over time. 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. Ageing is an important part of all human societies reflecting the biological changes that occur, but also reflecting cultural and societal conventions. Ageing is among the largest known risk factors for most human diseases. Roughly 100,000 people worldwide die each day of age-related causes.
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 age-expectations of how people should act as they grow older) and "biological ageing" (an organism's physical state as it ages). 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). 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 adopt new technologies and to need education, the latter of which tend to lose political significance for people in the ageing process. Older people have different requirements from society and government as opposed to young people and frequently differing values as well, such as for property and pension rights. 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, or at least different, political influence.
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) having negligible senescence give hope to achieve negligible senescence (cancel ageing) for younger humans, reverse ageing or at least significantly delay it.
However, human ageing may differ in significant respects from the ageing of worms and even mice. Recent progress in deciphering the ageing of human cells aged in culture as first described by Leonard Hayflick led to the demonstration that human cells age largely because of a genetic "clock" in the DNA region known as the telomere. By isolating the telomerase gene, scientists then at Geron demonstrated that telomerase was an immortalizing enzyme likely necessary for the immortality of germ-line cells, but absent in most cells in the body. This observation led to the mainstreaming of the concept of regenerative medicine, in which human embryonic stem cells may potentially be used to repair aged tissues with young cells, and induced pluripotent stem (iPS) cell technology capable of making cells of various kinds that are potentially useful in repairing tissues for the treatment of age-related degenerative diseases.
Some aspects of bacterial senescence may lend support to contemporary theories of ageing, including the free radical, antagonistic pleiotropy, and disposable soma theories. Ageing is the major cause of mortality in the developed world.
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 the increased risk of disease. Ageing is among the largest known risk factors for most human diseases. 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 genetically influenced "conditions," potentially "treatable".
There are three main metabolic pathways which influence the rate of ageing: caloric restriction, the insulin/IGF-1-like signalling pathway, and the activity levels of the electron transport chain. Before these were discovered, ageing was considered to be a progressive decline in function. It is likely that these three pathways affect ageing separately, because targeting them simultaneously leads to additive increases in lifespan.
Ageing and longevity are determined by a complex mixture of environmental and genetic factors. The genetic aspect has been demonstrated in studies of centenarians, and in model organisms where single-gene mutations have been shown to dramatically increase lifespan. These genes have homologues in the mammalian genome, making them useful both in studying ageing and in identifying potential targets for interventions which increase lifespan. These genes also increase lifespan in mice, and in some cases have been shown to associate with human longevity.
Numerous species show very low signs of ageing ("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 and lobster.
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. Stem cells regenerative capacity is affected by the age of the recipient.
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 by 30%.
In addition to genetic ties to lifespan, diet (specifically, caloric restriction) has been shown to substantially affect lifespan in many animals, including delay or prevention of many age-related diseases. Typically, this involves caloric intake to 60–70% of what an ad libitum animal would consume, while still maintaining proper nutrient intake. In rodents, it has been shown to increase lifespan by up to 50%; it also works for many other species beyond mice, including species as diverse as yeast and Drosophila, and likely includes primates as well. There are two major studies of caloric restriction being performed in rhesus monkeys, one at the US National Institutes of Health, and the other at the University of Wisconsin-Madison. The basis for caloric restriction remains unclear, though it is likely mediated by nutrient-sensing pathways such as the mTOR pathway.
Evidence in both animals and humans suggests that resveratrol may be a caloric restriction mimetic.
In his book How and Why We Age, Hayflick says that caloric restriction may not be effective in humans, citing data from the Baltimore Longitudinal Study of Aging which shows that being thin does not favour longevity.[need quotation to verify]
Of the roughly 150,000 people who die each day across the globe, about two thirds—100,000 per day—die of age-related causes. In industrialised nations, the proportion is much higher, reaching 90%.
At present, the biological basis of ageing is unknown. The rate of ageing varies substantially across different species, and this, to a large extent, is genetically based. In model organisms and laboratory settings, researchers have demonstrated 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. Even in the relatively simple and short-lived organisms, the mechanisms 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).
A primary model organism for studying ageing is the nematode C. elegans, because of their short lifespan, the ability to easily perform genetic manipulations or knock down genes with RNA interference, and other factors. Most known mutations and RNA interference targets that extend lifespan were first discovered in C. elegans.
Steady decline in many cognitive processes is seen across the lifespan, accelerating from the twenties or even thirties. 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. 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. 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. 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.
Healthy ageing implies optimal well-being in spite of barriers resulting from age. The global population is ageing and will continue to have communication inabilities unless barriers of communication with the elderly are more highly promoted. Sensory impairments include hearing and vision deficits, which can cause communication barriers. Changes in cognition, hearing, and vision are easily associated with healthy ageing and can causes problems when diagnosing dementia and aphasia due to the similarities.
Hearing loss is a common condition among ageing adults. Common conditions that can increase the risk of hearing loss in elderly people are high blood pressure, diabetes or the use of certain medications harmful to the ear. Hearing aids are commonly referred to as personal amplifying systems, which can generally improve hearing by about 50%.
Hearing loss among the aged community lessens elders' ability to compensate for other age related social and/or physical problems. Communication problems of elderly adults can be greatly impacted by mechanical problems such as: the translation of ideas into linguistic representation or expression, the perception of linguistic stimuli or the derivation of an idea from a given unit of disclosure. Changes in these mechanical problems are more important than changes in linguistic knowledge. The main goal of hearing aids is to improve communication and quality of life, not just to restore hearing.Presbycusis is an example of a hearing deficit that cannot be corrected by hearing aids. Presbycusis, the alteration of hearing sensitivity associated with normal hearing loss, is caused by the decreased amount of hair cells of the inner ear. This is normally caused by long periods of distressing noise that diminish the hair cells which with increasing age will not grow back. Presbycusis and other such hearing-related problems promote social withdrawal, as individuals begin to lose touch with the world around them. Hearing loss among the aged community lessens elders' ability to compensate for other age-related social and/or physical problems. This impairment can cause elders to lose touch of social skills because they may have trouble keeping up with fast-paced or hearing different pitched voices in conversation.
The interpretation of facial expressions and mouthing can be difficult to understand when an individual has a visual impairment. Such problems hinder the ability of people to understand stimuli and translate information pertaining to perception with their brain for analysis. Non-verbal communication is important in effective communication and elders with vision loss are more likely to misinterpret or read the other person's actions in a wrong way. Visual impairments also cause a loss in positive perceptions of the environment around them. This can lead to isolation and possible depression in elderly people. Macular degeneration is a common cause of vision loss in elderly people. It diminishes the macula of the eye, which is responsible for clear vision. It causes progressive loss of central vision and possible loss of colour vision. This degeneration is caused by systemic changes in the circulation of waste products and growth of abnormal vessels around the retina causing the photoreceptors not to receive proper images. Though ageing almost always causes this, other possible effects and risk factors include smoking, obesity, family history and excessive sunlight exposure.
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. 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. 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 and BRCA1.
The biological mechanisms which regulate lifespan evolved several hundred million years ago.
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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:
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. The casual terms "twentysomething", "thirtysomething", etc. are also in use to describe people by decades of age, along with the systematic terms such as "vicenarian", "tricenarian", "quadragenarian", etc.
Differences are sometimes made between populations of elderly people. Divisions are sometimes made between the young old (65–74), the middle old (75–84) and the oldest old (85+).
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. 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 for 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 (虛歲) with respect to common ageing which is called Zhousui (周歲). 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, 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. In parts of Tibet, age is counted from conception i.e. one is usually 9 months old when one is born.
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.
There are variations in many countries as to what age a person legally becomes an adult.
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.
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.
As life expectancy rises and birth rates decline in developed countries, the median age itself rises accordingly. According to the United Nations, this process is taking place in nearly every country in the world. 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. 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.
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.
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. 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.
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 the Medicare system in the United States decreased elderly spending on home health care by 12.5 percent per year between 1996 and 2000. This would suggest that the impact of ageing populations on health care costs is not inevitable.
In United States prisons, medical costs for an ageing inmate could be above $100 per day as of July 2007, while typical inmates cost $33 per day. Most State DOCs report spending more than 10 percent of the annual budget on elderly care. That is expected to rise over the next 10–20 years. Some states have talked about releasing ageing inmates early.
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. Social support and personal control are possibly the two most important factors that predict well-being, morbidity and mortality in adults. 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.
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, though personal control may have less impact on specific measures of health. 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.
Religion is 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. 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.
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 well-being and reduced mortality. 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. This finding is generally stronger for men than women, 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.
Seniors’ subjective health remains relatively stable while objective health worsens with age. Furthermore, it seems that the perceived health improves with age when objective health is controlled in the equation. This phenomenon is known as the paradox of ageing. People's expectations concerning health co-evolve with the health norms surrounding one's age. Elderly people often associate their functional and physical decline with the normal ageing process. The elderly may actually enhance their perception of their own health through social comparison; for instance, the older people get, the more they may consider themselves in better health than their same-aged peers. Hence, the older a person becomes and the more their actual health declines, the greater the potential role is for social comparison processes to create a gap between a person's objective and subjective health.
Retirement, a common transition faced by the elderly, may have both positive and negative consequences.
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.
Successful ageing consists of three components:
A greater number of people self-report successful ageing than those that strictly meet these criteria.
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. The terms "healthy ageing" 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:
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 access to meta data for these questions as well as links to obtain respondent data from the originating surveys.
Though many scientists state that radical life extension, delaying and stopping ageing are achievable, 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 2012 the Longevity political parties started in Russia, then in the USA, Israel and the Netherlands. These parties aim to provide political support to anti-ageing and radical life extension research and technologies and want to ensure the fastest possible and at the same time the softest 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.
Since ageing is regarded as cause or major risk factor of the age related diseases and many other causes of mortality there are growing effort in ageing research and stopping ageing thus extending healthy lifespan.  There are several prizes for extending lifespan and slowing ageing in mammals such as Mprize of Methuselah Foundation, Palo Alto Longevity Prize and others. Several companies and organisations, such as Google Calico, Human Longevity, Inc of Craig Venter, Quantum Pharmaceuticals, SENS Research FoundationScience against aging foundation, declared stoping or delaying ageing as their goal.
Many scientists who study the biology of ageing believe that the development of interventions which slow ageing is inevitable. Several drugs and food supplements 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.
There are three main signalling pathways which influence the rate of ageing: caloric restriction, the insulin/IGF-1-like signalling pathway, and the activity levels of the electron transport chain.
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. 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.
Ronald A. DePinho, a cancer geneticist at the Dana-Farber Cancer Institute and Harvard Medical School, published a paper 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. 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 anti-ageing treatments using this discovery.
mTOR inhibition and the frequent activation of autophagy has been shown to increase longevity in model organisms such as yeast, flies and mice. mTor inhibition and autophagy have also been linked to insulin sensitivity and the reduction of reactive oxygen species (ROS) damage, which is another major proposed cause to ageing. It has become clear that autophagy activation in the body by mTOR inhibition increases longevity. mTOR inhibition reduces ROS damage by activating autophagy, which will recycle the damaged parts of cells and re use them for functioning parts. This process reduces ROS damage to a reasonable amount, therefore increasing longevity. mTOR inhibition has also been linked to other major ageing diseases. mTOR inhibition has helped treat neurodegenerative diseases like Alzheimer’s in mice. It has also been used to reduce tumor growth in several cancers including renal, breast and several other rare cancers. Finally mTOR inhibition is also linked to reducing obesity and increasing immune function. The mTOR inhibition reduces the likelihood of diet induced and age induced obesity in mice, but in some cases led to glucose intolerance. Caloric restriction and exercise are two ways to activate autophagy and inhibit mTOR which can help resolve all of these common age related health issues.
The cellular balance between energy generation and consumption (energy homeostasis) requires tight regulation during ageing. In 2011, it was demonstrated that acetylation levels of AMP-activated protein kinase change with age in yeast and that preventing this change slows yeast ageing.
Caloric restriction substantially affects lifespan in many animals, including the ability to delay or prevent many age-related diseases. Evidence in both animals and humans suggests that resveratrol may be a caloric restriction mimetic.
Most known genetic interventions in C. elegans increase lifespan by 1.5 to 2.5-fold. As of 2009, the record for lifespan extension in C. elegans is a single-gene mutation which increases adult survival by tenfold. The strong conservation of some of the mechanisms of ageing discovered in model organisms imply that they may be useful in the enhancement of human survival. However, the benefits may not be proportional; longevity gains are typically greater in C. elegans than fruit flies, and greater in fruit flies than in mammals. One explanation for this is that mammals, being much longer-lived, already have many traits which promote lifespan. However, there are still opportunities for healthy human life to be extended beyond its current levels by pharmacological interventions.
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