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. 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.[2]

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).[3]

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+). However, problematic in this is that 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. 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.

Recent scientific successes in rejuvenation and extending a lifespan of model animals (mice-2.5 times, yeast -15 times, nematodes-10 times) and discovery of variety of species (including humans of advanced ages) [4] having negligible senescence give hope to achieve negligible senescence (cancel ageing) for younger humans, reverse ageing or at least significantly delay it.

Contents

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.[5] 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

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."

Indeed, ageing is not an unavoidable property of life. Instead, it is the result of a genetic program. 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[6] and lobster.[7][8]

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.

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.[9] 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 30-50% 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%. 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. 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.

Drug companies are currently searching for ways to mimic the lifespan-extending effects of caloric restriction without having to severely reduce food consumption.

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 Ageing show that being thin does not favour longevity.

Dividing the lifespan

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:

Ages can also be divided by decade:

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 is an American neologism referring to someone between the ages of 8 and 14.[10] The casual terms "twentysomething", "thirtysomething", etc. are also in use to describe people by decades of age.

Cultural variations

In some cultures (for example Serbian) 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 (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, because conception is already considered to be the start of the life span, and another difference is the ageing day: Xusui grows up at the Spring Festival (aka. Chinese New Year's Day), while Shuo An grows up at one's birthday.

Society

Legal

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 and marketing

The economics of ageing are also of great importance. Children and teenagers have little money of their own, but most of it is available for buying consumer goods. They also have considerable impact on how their parents spend money.

Young adults are an even more valuable cohort. They often have an income but few responsibilities such as a mortgage or children. They do not yet have set buying habits and are more open to new products.

The young are thus the central target of marketers.[11]

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.[12]

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.[13]

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.[14] 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 10–20 years. Some states have talked about releasing ageing inmates early.[15]

Cognitive effects

Steady decline in many cognitive processes is seen across the lifespan, accelerating from the 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. 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. 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.[3] 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.[16]

Coping and well-being

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.[17][18][19] Social support and personal control are possibly the two most important factors that predict well-being, morbidity and mortality in adults.[20] 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.[21]

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,[22][23] though personal control may have less impact on specific measures of health.[19] 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.[24]

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.[25] Religious commitment may also be associated with reduced mortality, though 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.[26]

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 well-being and reduced mortality.[27][28] 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.[29] This finding is generally stronger for men than women,[28] 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.[29]

Retirement

Retirement, a common transition faced by the elderly, may have both positive and negative consequences.[30]

Societal impact

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.[2] In industrialised nations, the proportion is much higher, reaching 90%.[2]

Societal ageing refers to the demographic ageing of populations and societies.[31] Cultural differences in attitudes to ageing have been studied.

Emotional improvement

Given the physical and cognitive declines seen in ageing, a surprising finding is that emotional experience improves with age. Older adults are better at regulating their emotions and experience negative affect less frequently than younger adults and show a positivity effect in their attention and memory. The emotional improvements show up in longitudinal studies as well as in cross-sectional studies and so cannot be entirely due to only the happier individuals surviving.

Successful ageing

The concept of successful ageing can be traced back to the 1950s, and 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.[32][33]

Successful ageing consists of three components:[34]

  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.[32]

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.[35] The terms "healthy ageing"[32] "optimal ageing" have been proposed as alternatives to successful ageing.

Six suggested dimensions of successful ageing include:[19]

  1. No physical disability over the age of 75 as rated by a physician;
  2. Good subjective health assessment (i.e. good self-ratings of one's health);
  3. Length of undisabled life;
  4. Good mental health;
  5. Objective social support;
  6. 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.

Theories

Biological theories

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). 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.[36] 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.

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

Genetic theories

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.

Examples include:

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.

  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

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.[3] 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.[45] There are research data suggesting that the elderly who do become detached from society as those were initially reclusive individuals, and such disengagement is not purely a response to ageing.[3]
Activity theory
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.[45] 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.[3] There are also data which query whether, as activity theory implies, greater social activity is linked with well-being in adulthood.[45]
Selectivity 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.[45]
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.[21] 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

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.[46]

Small doses of heavy water increase fruit-fly lifespan by 30%, but large doses are toxic to complex organisms.

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.[47] 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.[48] 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.[49]

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.[50] The mice lived 26% longer than normal.[51]

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.[52]

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%.[53] Rapamycin is generally used to suppress the immune system and prevent the rejection of transplanted organs. 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."

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.[54]

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 mitogen-activated protein kinase.[55] 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[56] 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 anti-ageing 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.[57]

Age in prenatal development is normally measured in gestational age, taking the last menstruation of the woman 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 access to meta data for these questions as well as links to obtain respondent data from the originating surveys.

See also

Notes

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  2. ^ a b c Aubrey D.N.J, de Grey (2007). "Life Span Extension Research and Public Debate: Societal Considerations" (PDF). Studies in Ethics, Law, and Technology 1 (1, Article 5). doi:10.2202/1941-6008.1011. http://www.mfoundation.org/files/sens/ENHANCE-PP.pdf. Retrieved March 20, 2009. 
  3. ^ a b c d e Stuart-Hamilton, Ian (2006). The Psychology of Ageing: An Introduction. London: Jessica Kingsley Publishers. ISBN 1-84310-426-1. 
  4. ^ http://longevity-science.org/Mortality_Deceleration.html
  5. ^ Ainul Hayat. Edited by Hakim Syed Zillur Rahman, Ibn Sina Academy of Medieval Medicine and Sciences. 2007. ISBN 978-81-901362-9-7
  6. ^ Physiological Basis of Ageing and Geriatrics, by Paola S. Timiras, p. 26, Informa Health Care, 2003, ISBN 0849309484
  7. ^ Jacob Silverman. "Is there a 400 pound lobster out there?". howstuffworks. http://animals.howstuffworks.com/marine-life/400-pound-lobster.htm/printable. 
  8. ^ David Foster Wallace (2005). Consider the Lobster and Other Essays. Little, Brown & Company. ISBN 0-31-615611-6. 
  9. ^ Hanahan D, Weinberg RA (2000). "The hallmarks of cancer". Cell 100 (1): 57–70. doi:10.1016/S0092-8674(00)81683-9. PMID 10647931. 
  10. ^ "Special Issues for Tweens and Teens". Media Awareness Network. 2010. http://www.media-awareness.ca/english/parents/marketing/issues_teens_marketing.cfm. Retrieved 26 January 2011. 
  11. ^ Krulwich, Robert (2006). "Does Age Quash Our Spirit of Adventure?". All Things Considered. NPR. http://www.npr.org/templates/story/story.php?storyId=5652676. Retrieved 2006-08-22. 
  12. ^ Saltman, R.B.; Dubois, H.F.W.; Chawla, M. (2006). "The Impact Of Ageing On Long-term Care In Europe And Some Potential Policy Responses". International Journal of Health Services 36 (4): 719–746. doi:10.2190/AUL1-4LAM-4VNB-3YH0. PMID 17175843. http://baywood.metapress.com/index/AUL14LAM4VNB3YH0.pdf. Retrieved 2008-02-11. 
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  18. ^ Windsor TD, Anstey KJ, Butterworth P, Luszcz MA, Andrews GR (2007). "The role of perceived control in explaining depressive symptoms associated with driving cessation in a longitudinal study". Gerontologist 47 (2): 215–23. doi:10.1093/geront/47.2.215. PMID 17440126. 
  19. ^ a b c Diane F. Gilmer; Aldwin, Carolyn M. (2003). Health, illness, and optimal ageing: biological and psychosocial perspectives. Thousand Oaks: Sage Publications. ISBN 0-7619-2259-8. 
  20. ^ Smith GC, Kohn SJ, Savage-Stevens SE, Finch JJ, Ingate R, Lim YO (2000). "The effects of interpersonal and personal agency on perceived control and psychological well-being in adulthood". Gerontologist 40 (4): 458–68. doi:10.1093/geront/40.4.458. PMID 10961035. 
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References

External links

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