Ageing

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Ageing or aging (see spelling differences) is the process of becoming older. The term refers especially to humans, many other animals, and fungi, whereas for example bacteria, perennial plants and some simple animals are potentially biologically immortal. [1] Furthermore, ageing connotes a biological and social construct. [2] It is usually associated with dynamic changes in the biological, psychological, physiological, environmental, behavioural and social processes. [3] In the broader sense, ageing can refer to single cells within an organism which have ceased dividing (cellular senescence) or to the population of a species (population ageing). [4]

Contents

In humans, ageing represents the accumulation of changes in a human being over time [5] and can encompass physical, psychological, and social changes. Reaction time, for example, may slow with age, while memories and general knowledge typically increase. Ageing increases the risk of human diseases: [6] of the roughly 150,000 people who die each day across the globe, about two-thirds die from age-related causes. [7]

Current ageing theories are assigned to the damage concept, whereby the accumulation of damage (such as DNA oxidation) may cause biological systems to fail, or to the programmed ageing concept, whereby problems with the internal processes (epigenomic maintenance such as DNA methylation [8] ) may cause ageing. Programmed ageing should not be confused with programmed cell death (apoptosis). Additionally, there can be other reasons, which can speed up the rate of ageing in organisms including human beings like obesity [9] [10] and compromised immune system.

Biologically, ageing results from the impact of the accumulation of a wide range of molecular and cellular damage over time. Thus, this leads to a gradual decline in physical and mental capacity, a growing risk of diseases, and ultimately, death. These changes are usually consistent, and they are associated with a person’s age in years. While some people aged 70 years may be strong and enjoy good health, others who are 70 years may be weak and require others to help them. [11]

Definitions

There are multiple ways to define ageing. Functional age measures age by capability and takes into account social, psychological, and physiological age. [12] Chronological age is based on the calendar year, from an individual's birth date to death date. [13]

Mortality can be used to define biological ageing, an organism's increased rate of death as it progresses throughout its life cycle. [14]  The processes and performance decline and bodily structure changes typical to chronological age. [15]

Another way to define ageing is through two types of functional definitions: [14]

An important distinction to make is that biological ageing is not the same thing as the accumulation of diseases related to old age; disease is a blanket term used to describe a process within an organism that causes a decrease in its functional ability. [14]

Ageing versus immortality

Immortal Hydra, a relative of the jellyfish Hydras (8).JPG
Immortal Hydra , a relative of the jellyfish

Human beings and members of other species, especially animals, age and die. Fungi, too, can age. [16] In contrast, many species can be considered potentially immortal: for example, bacteria fission to produce daughter cells, strawberry plants grow runners to produce clones of themselves, and animals in the genus Hydra have a regenerative ability by which they avoid dying of old age.

Early life forms on Earth, starting at least 3.7 billion years ago, [17] were single-celled organisms. Such organisms (Prokaryotes, Protozoans, algae) multiply by fission into daughter cells; thus do not age and are potentially immortal under favorable conditions. [18] [19]

Ageing and mortality of the individual organism became possible with the evolution of sexual reproduction, [20] which occurred with the emergence of the fungal/animal kingdoms approximately a billion years ago, and the evolution of seed-producing plants 320 million years ago. The sexual organism could henceforth pass on some of its genetic material to produce new individuals and could itself become disposable with respect to the survival of its species. [20] This classic biological idea has however been perturbed recently by the discovery that the bacterium E. coli may split into distinguishable daughter cells, which opens the theoretical possibility of "age classes" among bacteria. [21]

Even within humans and other mortal species, there are cells with the potential for immortality: cancer cells which have lost the ability to die when maintained in a cell culture such as the HeLa cell line, [22] and specific stem cells such as germ cells (producing ova and spermatozoa). [23] In artificial cloning, adult cells can be rejuvenated to embryonic status and then used to grow a new tissue or animal without ageing. [24] Normal human cells however die after about 50 cell divisions in laboratory culture (the Hayflick Limit, discovered by Leonard Hayflick in 1961). [22]

Signs of ageing

Enlarged ears and noses of old humans are sometimes blamed on continual cartilage growth, but the cause is more probably gravity. Senescence.JPG
Enlarged ears and noses of old humans are sometimes blamed on continual cartilage growth, but the cause is more probably gravity.
Age dynamics of the body mass (1, 2) and mass normalized to height (3, 4) of men (1, 3) and women (2, 4). Age dynamics of the body mass.svg
Age dynamics of the body mass (1, 2) and mass normalized to height (3, 4) of men (1, 3) and women (2, 4).
Comparison of a normal aged brain (left) and a brain affected by Alzheimer's disease (right). Alzheimer's disease brain comparison.jpg
Comparison of a normal aged brain (left) and a brain affected by Alzheimer's disease (right).

A number of characteristic ageing symptoms are experienced by a majority or by a significant proportion of humans during their lifetimes.

Dementia becomes more common with age. [53] About 3% of people between the ages of 65 and 74, 19% between 75 and 84, and nearly half of those over 85 years of age have dementia. [54] The spectrum ranges from mild cognitive impairment to the neurodegenerative diseases of Alzheimer's disease, cerebrovascular disease, Parkinson's disease and Lou Gehrig's disease. Furthermore, many types of memory decline with ageing, but not semantic memory or general knowledge such as vocabulary definitions, which typically increases or remains steady until late adulthood [55] (see Ageing brain). Intelligence declines with age, though the rate varies 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. [56] There are changes to the brain: after 20 years of age there is a 10% reduction each decade in the total length of the brain's myelinated axons. [57] [58]

Age can result in visual impairment, whereby non-verbal communication is reduced, [59] which can lead to isolation and possible depression. Older adults, however, may not suffer depression as much as younger adults, and were paradoxically found to have improved mood despite declining physical health. [60] Macular degeneration causes vision loss and increases with age, affecting nearly 12% of those above the age of 80. [61] This degeneration is caused by systemic changes in the circulation of waste products and by growth of abnormal vessels around the retina. [62] Other visual diseases that often appear with age would be cataracts and glaucoma. A cataract occurs when the lens of the eye becomes cloudy making vision blurry and eventually causing blindness if untreated. [63] They develop over time and are seen most often with those that are older. Cataracts can be treated through surgery. Glaucoma is another common visual disease that appears in older adults. Glaucoma is caused by damage to the optic nerve causing vision loss. [64] Glaucoma usually develops over time but there are variations to glaucoma, and some have sudden onset. There are a few procedures for glaucoma but there is no cure or fix for the damage once it has happened. Prevention is the best measure in the case of glaucoma. [64]

A distinction can be made between "proximal ageing" (age-based effects that come about because of factors in the recent past) and "distal ageing" (age-based differences that can be traced to a cause in a person's early life, such as childhood poliomyelitis). [56]

Ageing is among the greatest known risk factors for most human diseases. [65] Of the roughly 150,000 people who die each day across the globe, about two-thirds—100,000 per day—die from age-related causes. In industrialized nations, the proportion is higher, reaching 90%. [7] [66] [67]

Biological basis

95-year-old woman holding a five-month-old boy Old woman with young baby boy.JPG
95-year-old woman holding a five-month-old boy

At present, researchers are only just beginning to understand the biological basis of ageing even in relatively simple and short-lived organisms such as yeast. [68] Less still is known of mammalian ageing, in part due to the much longer lives of even small mammals such as the mouse (around 3 years). A model organism for the study of ageing is the nematode C. elegans . Thanks to its short lifespan of 2–3 weeks, our ability to easily perform genetic manipulations or to suppress gene activity with RNA interference, or other factors. [69] Most known mutations and RNA interference targets that extend lifespan were first discovered in C. elegans. [70]

The factors proposed to influence biological ageing [71] [ better source needed ] fall into two main categories, programmed and damage-related. [72] Programmed factors follow a biological timetable, perhaps one that might be a continuation of the one that regulates childhood growth and development. This regulation would depend on changes in gene expression that affect the systems responsible for maintenance, repair and defense responses. Damage-related factors include internal and environmental assaults to living organisms that induce cumulative damage at various levels. [72] A third, novel, concept is that ageing is mediated by vicious cycles. [65]

Molecular and cellular hallmarks of ageing

In a detailed review, Lopez-Otin and colleagues (2013), who discuss ageing through the lens of the damage theory, propose nine metabolic "hallmarks" of ageing in various organisms but especially mammals: [73]

Metabolic pathways involved in ageing

There are three main metabolic pathways which can influence the rate of ageing, discussed below:

It is likely that most of these pathways affect ageing separately, because targeting them simultaneously leads to additive increases in lifespan. [75]

Programmed factors

The rate of ageing varies substantially across different species, and this, to a large extent, is genetically based. For example, numerous perennial plants ranging from strawberries and potatoes to willow trees typically produce clones of themselves by vegetative reproduction and are thus potentially immortal, while annual plants such as wheat and watermelons die each year and reproduce by sexual reproduction. In 2008 it was discovered that inactivation of only two genes in the annual plant Arabidopsis thaliana leads to its conversion into a potentially immortal perennial plant. [76] The oldest animals known so far are 15,000-year-old Antarctic sponges, [77] which can reproduce both sexually and clonally.

Clonal immortality apart, there are certain species whose individual lifespans stand out among Earth's life-forms, including the bristlecone pine at 5062 years [78] or 5067 years, [77] invertebrates like the hard clam (known as quahog in New England) at 508 years, [79] the Greenland shark at 400 years, [80] various deep-sea tube worms at over 300 years, [81] fish like the sturgeon and the rockfish, and the sea anemone [82] and lobster. [83] [84] Such organisms are sometimes said to exhibit negligible senescence. [85] The genetic aspect has also been demonstrated in studies of human centenarians.

In laboratory settings, researchers have demonstrated that selected alterations in specific genes can extend lifespan quite substantially in yeast and roundworms, less so in fruit flies and less again in mice. Some of the targeted genes have homologues across species and in some cases have been associated with human longevity. [86] Studies by Becca Levy, an associate professor of epidemiology and psychology at the Yale School of Public Health, have found that positive beliefs about ageing may also increase life span. [87]

An elderly Somali woman Habibaadansalat.jpg
An elderly Somali woman

Evolution of ageing

Life span, like other phenotypes, is selected for in evolution. Traits that benefit early survival and reproduction will be selected for even if they contribute to an earlier death. Such a genetic effect is called the antagonistic pleiotropy effect when referring to a gene (pleiotropy signifying the gene has a double function – enabling reproduction at a young age but costing the organism life expectancy in old age) and is called the disposable soma effect when referring to an entire genetic programme (the organism diverting limited resources from maintenance to reproduction). [20] The biological mechanisms which regulate lifespan probably evolved with the first multicellular organisms more than a billion years years ago [70] . However, even single-celled organisms such as yeast have been used as models in ageing, hence ageing has its biological roots much earlier than multi-cellularity. [122]

Prevention and delay

Lifestyle

Caloric restriction substantially affects lifespan in many animals, including the ability to delay or prevent many age-related diseases. [145] Typically, this involves caloric intake of 60–70% of what an ad libitum animal would consume, while still maintaining proper nutrient intake. [145] In rodents, this has been shown to increase lifespan by up to 50%; [146] similar effects occur for yeast and Drosophila. [145] No lifespan data exist for humans on a calorie-restricted diet, [103] but several reports support protection from age-related diseases. [147] [148] Two major ongoing studies on rhesus monkeys initially revealed disparate results; while one study, by the University of Wisconsin, showed that caloric restriction does extend lifespan, [149] the second study, by the National Institute on Aging (NIA), found no effects of caloric restriction on longevity. [150] Both studies nevertheless showed improvement in a number of health parameters. Notwithstanding the similarly low calorie intake, the diet composition differed between the two studies (notably a high sucrose content in the Wisconsin study), and the monkeys have different origins (India, China), initially suggesting that genetics and dietary composition, not merely a decrease in calories, are factors in longevity. [103] However, in a comparative analysis in 2014, the Wisconsin researchers found that the allegedly non-starved NIA control monkeys in fact are moderately underweight when compared with other monkey populations, and argued this was due to the NIA's apportioned feeding protocol in contrast to Wisconsin's truly unrestricted ad libitum feeding protocol. [151] They conclude that moderate calorie restriction rather than extreme calorie restriction is sufficient to produce the observed health and longevity benefits in the studied rhesus monkeys. [152]

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 ] [153] However, there may be confounders, e.g. smoking reduces both appetite and lifespan. Similarly, it is sometimes claimed that moderate obesity in later life may improve survival, but newer research has identified confounding factors such as weight loss due to terminal disease. Once these factors are accounted for, the optimal body weight above age 65 corresponds to a leaner body mass index of 23 to 27. [154]

Alternatively, the benefits of dietary restriction can also be found by changing the macro nutrient profile to reduce protein intake without any changes to calorie level, resulting in similar increases in longevity. [155] [156] Dietary protein restriction not only inhibits mTOR activity but also IGF-1, two mechanisms implicated in ageing. [100] Specifically, reducing leucine intake is sufficient to inhibit mTOR activity, achievable through reducing animal food consumption. [157] [158]

The Mediterranean diet is credited with lowering the risk of heart disease and early death. [159] [160] The major contributors to mortality risk reduction appear to be a higher consumption of vegetables, fish, fruits, nuts and monounsaturated fatty acids, i.e., olive oil. [161]

The amount of sleep has an impact on mortality. People who live the longest report sleeping for six to seven hours each night. [162] [163] Lack of sleep (<5 hours) more than doubles the risk of death from cardiovascular disease, but too much sleep (>9 hours) is associated with a doubling of the risk of death, though not primarily from cardiovascular disease. [164] Sleeping more than 7 to 8 hours per day has been consistently associated with increased mortality, though the cause is probably other factors such as depression and socioeconomic status, which would correlate statistically. [165] Sleep monitoring of hunter-gatherer tribes from Africa and from South America has shown similar sleep patterns across continents: their average sleeping duration is 6.4 hours (with a summer/winter difference of 1 hour), afternoon naps (siestas) are uncommon, and insomnia is very rare (tenfold less than in industrial societies). [166]

Physical exercise may increase life expectancy. [167] People who participate in moderate to high levels of physical exercise have a lower mortality rate compared to individuals who are not physically active. [168] Moderate levels of exercise have been correlated with preventing ageing and improving quality of life by reducing inflammatory potential. [169] The majority of the benefits from exercise are achieved with around 3500 metabolic equivalent (MET) minutes per week. [170] For example, climbing stairs 10 minutes, vacuuming 15 minutes, gardening 20 minutes, running 20 minutes, and walking or bicycling for 25 minutes on a daily basis would together achieve about 3000 MET minutes a week. [170] Other research seems to suggest a relationship between regular physical exercise and cognitive functioning in old age. [171]

Avoidance of chronic stress (as opposed to acute stress) is associated with a slower loss of telomeres in most but not all studies, [172] [173] and with decreased cortisol levels. A chronically high cortisol level compromises the immune system, causes cardiac damage/arterosclerosis and is associated with facial ageing, and the latter in turn is a marker for increased morbidity and mortality. [174] [175] A meta-analysis shows that loneliness carries a higher mortality risk than smoking. [176] Stress can be countered by social connection, spirituality, and (for men more clearly than for women) married life, all of which are associated with longevity. [177] [178] [179] [180]

Medical intervention

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

Evidence in both animals and humans suggests that resveratrol may be a caloric restriction mimetic. [181]

As of 2015, metformin was under study for its potential effect on slowing ageing in the worm C.elegans and the cricket. [182] Its effect on otherwise healthy humans is unknown. [182]

Rapamycin was first shown to extend lifespan in eukaryotes in 2006 by Powers et al. who showed a dose-responsive effect of rapamycin on lifespan extension in yeast cells. [183] In a 2009 study, the lifespans of mice fed rapamycin were increased between 28 and 38% from the beginning of treatment, or 9 to 14% in total increased maximum lifespan. Of particular note, the treatment began in mice aged 20 months, the equivalent of 60 human years. [184] Rapamycin has subsequently been shown to extend mouse lifespan in several separate experiments, [185] [186] and is now being tested for this purpose in nonhuman primates (the marmoset monkey). [187]

Cancer geneticist Ronald A. DePinho and his colleagues published research on mice where telomerase activity was first genetically removed. Then, after the mice had prematurely aged, they restored telomerase activity by reactivating the telomerase gene. As a result, the mice were rejuvenated: Shrivelled testes grew back to normal and the animals regained their fertility. Other organs, such as the spleen, liver, intestines and brain, recuperated from their degenerated state. "[The finding] offers the possibility that normal human ageing could be slowed by reawakening the enzyme in cells where it has stopped working" says Ronald DePinho. However, activating telomerase in humans could potentially encourage the growth of tumours. [188]

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. [70] 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. [70]

Mitochondria-targeted antioxidant SkQ1 has been shown to extend the lifespan of mice. [189]

Research projects and prizes

Some research effort is directed to slow ageing and extend healthy lifespan. [190] [191] [192] In 1993, the Established populations for epidemiologic studies of the elderly, [193] also known as the Yale Health and Aging Study, showed the importance of physical activity and argued against negative stereotypes concerning old age.

The US National Institute on Aging currently funds an intervention testing programme, 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. [194] Previous age-related testing in mammals has proved largely irreproducible, because of small numbers of animals and lax mouse husbandry conditions.[ citation needed ] The intervention testing programme 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.

Several companies and organisations, such as Google Calico, Human Longevity, Craig Venter, Gero, [195] SENS Research Foundation, and Science for Life Extension in Russia, [196] declared stopping or delaying ageing as their goal.

Prizes for extending lifespan and slowing ageing in mammals exist. The Methuselah Foundation offers the Mprize. Recently, the $1 Million Palo Alto Longevity Prize was launched. It is a research incentive prize to encourage teams from all over the world to compete in an all-out effort to "hack the code" that regulates our health and lifespan. It was founded by Joon Yun. [197] [198] [199] [200] [201]

Society and culture

An elderly man 003 p4 dd.JPG
An elderly man

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

Most legal systems define a specific age for when an individual is allowed or obliged to do particular activities. These age specifications include voting age, drinking age, age of consent, age of majority, age of criminal responsibility, marriageable age, age of candidacy, and mandatory retirement age. Admission to a movie for instance, may depend on age according to a motion picture rating system. A bus fare might be discounted for the young or old. Each nation, government and non-governmental organisation has different ways of classifying age. In other words, chronological ageing may be distinguished from "social ageing" (cultural age-expectations of how people should act as they grow older) and "biological ageing" (an organism's physical state as it ages). [202]

Ageism cost the United States $63 billion in one year according to a Yale School of Public Health study. [203] In a UNFPA report about ageing in the 21st century, it highlighted the need to "Develop a new rights-based culture of ageing and a change of mindset and societal attitudes towards ageing and older persons, from welfare recipients to active, contributing members of society". [204] UNFPA said that this "requires, among others, working towards the development of international human rights instruments and their translation into national laws and regulations and affirmative measures that challenge age discrimination and recognise older people as autonomous subjects". [204] Older people's music participation contributes to the maintenance of interpersonal relationships and promoting successful ageing. [205] At the same time, older persons can make contributions to society including caregiving and volunteering. For example, "A study of Bolivian migrants who [had] moved to Spain found that 69% left their children at home, usually with grandparents. In rural China, grandparents care for 38% of children aged under five whose parents have gone to work in cities." [204]

Economics

A map showing median age figures for 2017 2017 world map, median age by country.svg
A map showing median age figures for 2017

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 have fewer legal privileges (if they are below the age of majority), 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, and frequently have differing values as well, such as for property and pension rights. [206]

In the 21st century, one of the most significant population trends is ageing. [207] Currently, over 11% of the world's current population are people aged 60 and older and the United Nations Population Fund (UNFPA) estimates that by 2050 that number will rise to approximately 22%. [204] Ageing has occurred due to development which has enabled better nutrition, sanitation, health care, education and economic well-being. Consequently, fertility rates have continued to decline and life expectancy has risen. Life expectancy at birth is over 80 now in 33 countries. Ageing is a "global phenomenon", that is occurring fastest in developing countries, including those with large youth populations, and poses social and economic challenges to the work which can be overcome with "the right set of policies to equip individuals, families and societies to address these challenges and to reap its benefits". [208]

As life expectancy rises and birth rates decline in developed countries, the median age rises accordingly. According to the United Nations, this process is taking place in nearly every country in the world. [209] 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. [210] 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. [210]

Among the most urgent concerns of older persons worldwide is income security. This poses challenges for governments with ageing populations to ensure investments in pension systems continues in order to provide economic independence and reduce poverty in old age. These challenges vary for developing and developed countries. UNFPA stated that, "Sustainability of these systems is of particular concern, particularly in developed countries, while social protection and old-age pension coverage remain a challenge for developing countries, where a large proportion of the labour force is found in the informal sector." [204]

The global economic crisis has increased financial pressure to ensure economic security and access to health care in old age. In order to elevate this pressure "social protection floors must be implemented in order to guarantee income security and access to essential health and social services for all older persons and provide a safety net that contributes to the postponement of disability and prevention of impoverishment in old age". [204]

It has been argued that population ageing has undermined economic development [211] and can lead to lower inflation because elderly individuals care especially strongly about the value of their pensions and savings Evidence suggests that pensions, while making a difference to the well-being of older persons, also benefit entire families especially in times of crisis when there may be a shortage or loss of employment within households. A study by the Australian Government in 2003 estimated that "women between the ages of 65 and 74 years contribute A$16 billion per year in unpaid caregiving and voluntary work. Similarly, men in the same age group contributed A$10 billion per year." [204]

Due to increasing share of the elderly in the population, health care expenditures will continue to grow relative to the economy in coming decades. This has been considered as a negative phenomenon and effective strategies like labour productivity enhancement should be considered to deal with negative consequences of ageing. [212]

Sociology

Christoffer Wilhelm Eckersberg: Ages of Man Menneske Aldrene (C. W. Eckersberg).png
Christoffer Wilhelm Eckersberg: Ages of Man

In the field of sociology and mental health, ageing is seen in five different views: ageing as maturity, ageing as decline, ageing as a life-cycle event, ageing as generation, and ageing as survival. [213] Positive correlates with ageing often include economics, employment, marriage, children, education, and sense of control, as well as many others. The social science of ageing includes disengagement theory, activity theory, selectivity theory, and continuity theory. Retirement, a common transition faced by the elderly, may have both positive and negative consequences. [214] As cyborgs currently are on the rise some theorists argue there is a need to develop new definitions of ageing and for instance a bio-techno-social definition of ageing has been suggested. [215]

There is a current debate as to whether or not the pursuit of longevity and the postponement of senescence are cost-effective health care goals given finite health care resources. Because of the accumulated infirmities of old age, bioethicist Ezekiel Emanuel, opines that the pursuit of longevity via the compression of morbidity hypothesis is a "fantasy" and that human life is not worth living after age 75; longevity then should not be a goal of health care policy. [216] This opinion has been contested by neurosurgeon and medical ethicist Miguel Faria, who states that life can be worthwhile during old age, and that longevity should be pursued in association with the attainment of quality of life. [217] Faria claims that postponement of senescence as well as happiness and wisdom can be attained in old age in a large proportion of those who lead healthy lifestyles and remain intellectually active. [218]

Health care demand

With age inevitable biological changes occur that increase the risk of illness and disability. UNFPA states that, [208]

"A life-cycle approach to health care – one that starts early, continues through the reproductive years and lasts into old age – is essential for the physical and emotional well-being of older persons, and, indeed, all people. Public policies and programmes should additionally address the needs of older impoverished people who cannot afford health care."

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. [219]

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. [220] 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.

It has been estimated that population ageing only explains 0.2 percentage points of the annual growth rate in medical spending of 4.3% since 1970. In addition, certain reforms to the Medicare system in the United States decreased elderly spending on home health care by 12.5% per year between 1996 and 2000. [221]

Self-perception

As humans age, their bodies begin to break down and their skin begins to look different, but people do not always welcome these changes to their appearance. [222]

Beauty standards have evolved over time, and as scientific research in cosmeceuticals has increased, the industry has also expanded; the kinds of products they produce (such as serums and creams) have gradually gained popularity and become a part of many people's personal care routine. [223] The cosmeceutical industry is currently the fastest growing beauty industry, with a market size of $49.5 billion for the year 2018. [224]

The increase in demand for cosmeceuticals has led scientists to find ingredients for these products in unorthodox places. For example, cryptomphalus aspersa secretion (or brown garden snail secretion) has been found to have antioxidant properties, increase skin cell proliferation, as well as increase extracellular proteins such as collagen and fibronectin (important proteins for cell proliferation). [225] Another substance used to prevent the physical manifestations of aging is onobotulinumtoxinA, the toxin injected for Botox. [226]

Generally, aversion to ageing is a Western attitude. However, in other places around the world, old age is celebrated and honored. In Korea, for example, a special party called hwangap is held to celebrate and congratulate an individual for turning 60 years old. [227]

Positive self-perceptions of aging are associated with better mental and physical health and well-being. [228] Positive self-perception of health has been correlated with higher well-being and reduced mortality among the elderly. [229] [230] Various reasons have been proposed for this association; people who are objectively healthy may naturally rate their health better as 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. [231] This finding is generally stronger for men than women, [230] though this relationship is not universal across all studies and may only be true in some circumstances. [231]

As people age, subjective health remains relatively stable, even though objective health worsens. [232] In fact, perceived health improves with age when objective health is controlled in the equation. [233] This phenomenon is known as the "paradox of ageing". This may be a result of social comparison; [234] for instance, the older people get, the more they may consider themselves in better health than their same-aged peers. [235] Elderly people often associate their functional and physical decline with the normal ageing process. [236] [237]

One way to help younger people experience what it feels like to be older is through an ageing suit. There are several different kinds of suits including the GERT (named as a reference to gerontology), the R70i exoskeleton, and the AGNES (Age Gain Now Empathy Suit) suits. [238] [239] [240] These suits create the feelings of the effects of aging by adding extra weight and increased pressure in certain points like the wrists, ankles and other joints. In addition, the various suits have different ways to impair vision and hearing to simulate the loss of these senses. To create the loss of feeling in hands that the elderly experience, special gloves are a part of the uniforms.

Use of these suits may help to increase the amount of empathy felt for the elderly and could be considered particularly useful for those who are either learning about aging, or those who work with the elderly, such as nurses or care center staff.

Empathy is another field that could benefit from the empathy these suits may cause. [238] [240] When designers understand what it feels like to have the impairments of old age, they can better design buildings, packaging, or even tools to help with the simple day-to-day tasks that are more difficult with less dexterity. Designing with the elderly in mind may help to reduce the negative feelings that are associated with the loss of abilities that the elderly face.

Successful ageing

The concept of successful ageing can be traced back to the 1950s and was popularized in the 1980s. Traditional definitions of successful ageing have emphasized absence of physical and cognitive disabilities. [241] In their 1987 article, Rowe and Kahn characterized successful ageing as involving three components: a) freedom from disease and disability, b) high cognitive and physical functioning, and c) social and productive engagement. [242] There are some differences in cultures which of these components are the most important. Most often across cultures social engagement was the most highly rated but depending on the culture the definition of successful ageing changes. [243]

Cultural references

The ancient Greek dramatist Euripides (5th century BC) describes the multiple-headed mythological monster Hydra as having a regenerative capacity which makes it immortal, which is the historical background to the name of the biological genus Hydra. The Book of Job (c. 6th century BC) describes human lifespan as inherently limited and makes a comparison with the innate immortality that a felled tree may have when undergoing vegetative regeneration. [244]

See also

Related Research Articles

Telomere Nucleotide sequences

A telomere is a region of repetitive nucleotide sequences associated with specialized proteins at the ends of linear chromosomes. Although there are different architectures, telomeres, in a broad sense, are a widespread genetic feature most commonly found in eukaryotes. In most, if not all species possessing them, they protect the terminal regions of chromosomal DNA from progressive degradation and ensure the integrity of linear chromosomes by preventing DNA repair systems from mistaking the very ends of the DNA strand for a double strand break.

Senescence Deterioration of function with age

Senescence or biologicalaging is the gradual deterioration of functional characteristics in living organisms. The word senescence can refer to either cellular senescence or to senescence of the whole organism. Organismal senescence involves an increase in death rates and/or a decrease in fecundity with increasing age, at least in the latter part of an organism's life cycle.

Life extension is the concept of extending the human lifespan, either modestly through improvements in medicine or dramatically by increasing the maximum lifespan beyond its generally-settled limit of 125 years.

Maximum life span is a measure of the maximum amount of time one or more members of a population have been observed to survive between birth and death. The term can also denote an estimate of the maximum amount of time that a member of a given species could survive between birth and death, provided circumstances that are optimal to that member's longevity.

A low-protein diet is a diet in which people decrease their intake of protein. A low-protein diet is used as a therapy for inherited metabolic disorders, such as phenylketonuria and homocystinuria, and can also be used to treat kidney or liver disease. Low protein consumption appears to reduce the risk of bone breakage, presumably through changes in calcium homeostasis. Consequently, there is no uniform definition of what constitutes low-protein, because the amount and composition of protein for an individual suffering from phenylketonuria would differ substantially from one suffering homocystinuria or tyrosinemia. The amount used by those with liver disease would still result in individuals being in nitrogen balance.

The free radical theory of aging (FRTA) states that organisms age because cells accumulate free radical damage over time. A free radical is any atom or molecule that has a single unpaired electron in an outer shell. While a few free radicals such as melanin are not chemically reactive, most biologically relevant free radicals are highly reactive. For most biological structures, free radical damage is closely associated with oxidative damage. Antioxidants are reducing agents, and limit oxidative damage to biological structures by passivating them from free radicals.

Calorie restriction mimetics (CRM), also known as energy restriction mimetics, are a hypothetical class of dietary supplements or drug candidates that would, in principle, mimic the substantial anti-aging effects that calorie restriction (CR) has on many laboratory animals and humans. CR is defined as a reduction in calorie intake of 20% to 50% without incurring malnutrition or a reduction in essential nutrients. An effective CRM would alter the key metabolic pathways involved in the effects of CR itself, leading to preserved youthful health and longer lifespan without the need to reduce food intake. The term was coined by Lane, Ingram, Roth of the National Institute on Aging in a seminal 1998 paper in the Journal of Anti-Aging Medicine, the forerunner of Rejuvenation Research. A number of genes and pathways have been shown to be involved the actions of CR in model organisms and these represent attractive targets for drug discovery and for developing CRM. However, no effective CRM have been identified to date.

Biogerontology Sub-field of gerontology

Biogerontology is the sub-field of gerontology concerned with the biological aging process, its evolutionary origins, and potential means to intervene in the process. The term "biogerontology" was coined by S. Rattan, and came in regular use with the start of the jorunal BIOGERONTOLOGY in 2000. It involves interdisciplinary research on the causes, effects, and mechanisms of biological aging. Biogerontologist Leonard Hayflick has said that the natural average lifespan for a human is around 92 years and, if humans do not invent new approaches to treat aging, they will be stuck with this lifespan. James Vaupel has predicted that life expectancy in industrialized countries will reach 100 for children born after the year 2000. Many surveyed biogerontologists have predicted life expectancies of more than three centuries for people born after the year 2100. Other scientists, more controversially, suggest the possibility of unlimited lifespans for those currently living. For example, Aubrey de Grey offers the "tentative timeframe" that with adequate funding of research to develop interventions in aging such as strategies for engineered negligible senescence, "we have a 50/50 chance of developing technology within about 25 to 30 years from now that will, under reasonable assumptions about the rate of subsequent improvements in that technology, allow us to stop people from dying of aging at any age". The idea of this approach is to use presently available technology to extend lifespans of currently living humans long enough for future technological progress to resolve any remaining aging-related issues. This concept has been referred to as longevity escape velocity.

Calorie restriction is a dietary regimen that reduces food intake without incurring malnutrition. "Reduce" can be defined relative to the subject's previous intake before intentionally restricting food or beverage consumption, or relative to an average person of similar body type.

Enquiry into the evolution of ageing aims to explain why a detrimental process such as aging would evolve, and why there is so much variability in the lifespans of living organisms. The classical theories of evolution suggest that environmental factors, such as predation, accidents, disease, starvation, ensure that most organisms living in natural settings will not live until old age, and so there will be very little pressure to conserve genetic changes that increase longevity. Natural selection will instead strongly favor genes which ensure early maturation and rapid reproduction, and the selection for genetic traits which promote molecular and cellular self-maintenance will decline with age for most organisms.

Eternal youth Physical immortality free of ageing

Eternal youth is the concept of human physical immortality free of ageing. The youth referred to is usually meant to be in contrast to the depredations of aging, rather than a specific age of the human lifespan. Eternal youth is common in mythology, and is a popular theme in fiction.

The DNA damage theory of aging proposes that aging is a consequence of unrepaired accumulation of naturally occurring DNA damage. Damage in this context is a DNA alteration that has an abnormal structure. Although both mitochondrial and nuclear DNA damage can contribute to aging, nuclear DNA is the main subject of this analysis. Nuclear DNA damage can contribute to aging either indirectly or directly.

The stem cell theory of aging postulates that the aging process is the result of the inability of various types of stem cells to continue to replenish the tissues of an organism with functional differentiated cells capable of maintaining that tissue's original function. Damage and error accumulation in genetic material is always a problem for systems regardless of the age. The number of stem cells in young people is very much higher than older people and thus creates a better and more efficient replacement mechanism in the young contrary to the old. In other words, aging is not a matter of the increase in damage, but a matter of failure to replace it due to a decreased number of stem cells. Stem cells decrease in number and tend to lose the ability to differentiate into progenies or lymphoid lineages and myeloid lineages.

The anti-aging movement is a social movement devoted to eliminating or reversing aging, or reducing the effects of it. A substantial portion of the attention of the movement is on the possibilities for life extension, but there is also interest in techniques such as cosmetic surgery which ameliorate the effects of aging rather than delay or defeat it.

Biomarkers of aging

Biomarkers of aging are biomarkers that could predict functional capacity at some later age better than chronological age. Stated another way, biomarkers of aging would give the true "biological age", which may be different from the chronological age.

Genetics of aging Overview of the genetics of aging

Genetics of aging is generally concerned with life extension associated with genetic alterations, rather than with accelerated aging diseases leading to reduction in lifespan.

The disposable soma theory of aging states that organisms age due to an evolutionary trade-off between growth, reproduction, and DNA repair maintenance. Formulated by Thomas Kirkwood, the disposable soma theory explains that an organism only has a limited amount of resources that it can allocate to its various cellular processes. Therefore, a greater investment in growth and reproduction would result in reduced investment in DNA repair maintenance, leading to increased cellular damage, shortened telomeres, accumulation of mutations, compromised stem cells, and ultimately, senescence. Although many models, both animal and human, have appeared to support this theory, parts of it are still controversial. Specifically, while the evolutionary trade-off between growth and aging has been well established, the relationship between reproduction and aging is still without scientific consensus, and the cellular mechanisms largely undiscovered.

Mitochondrial theory of ageing Theory

The mitochondrial theory of aging has two varieties: free radical and non-free radical. The first is one of the variants of the free radical theory of aging. It was formulated by J. Michel in 1980 and was developed in the works of A. V. Linnan (1989). The second was proposed by A. N. Lobachev in 1978.

The hallmarks of aging are the types of biochemical changes that occur in all organisms that experience biological aging and lead to a progressive loss of physiological integrity, impaired function and, eventually, death. They were first enumerated in a landmark paper in 2013 to conceptualize the essence of biological aging and its underlying mechanisms.

This timeline lists notable events in the history of research of senescence or biological aging. People have always been interested in how to make their lives longer and healthier in old age. Already the most anсient Egyptian, Indian and Chinese books contain reasoning about aging. Ancient Egyptians used garlic in large quantities to extend their lifespan. Hippocrates in his Aphorisms and Aristotle (384 – 322 BC) in On youth and old age expresses their opinions about reasons for old age and gave advice about lifestyle. Medieval Persian physician Ibn Sina, known in the West as Avicenna, summarized achievements of the earlier generations about this issue.

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