Ageing


Ageing or aging is the process of becoming older. The term refers especially to human beings, many animals, and fungi, whereas for example bacteria, perennial plants and some simple animals are potentially biologically immortal. In the broader sense, aging can refer to single cells within an organism which have ceased dividing or to the population of a species.
In humans, aging represents the accumulation of changes in a human being over time and can encompass physical, psychological, and social changes. Reaction time, for example, may slow with age, while knowledge of world events and wisdom may expand. Aging is among the greatest known risk factors for most human diseases: of the roughly 150,000 people who die each day across the globe, about two thirds die from age-related causes.
The causes of aging are uncertain; current theories are assigned to the damage concept, whereby the accumulation of damage may cause biological systems to fail, or to the programmed aging concept, whereby internal processes may cause aging. Programmed aging should not be confused with programmed cell death.

Definitions

Mortality can be used to define biological aging, which refers to an organism’s increased rate of death as it progresses throughout its lifecycle and increases its chronological age.  Another possible way to define aging is through functional definitions, of which there are two main types.  The first describes how varying types of deteriorative changes that accumulate in the life of a post-maturation organism can leave it vulnerable, leading to a decreased ability of the organism to survive.  The second is a senescence-based definition; this describes age-related changes in an organism that increase its mortality rate over time by negatively affecting its vitality and functional performance. An important distinction to make is that biological aging 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.

Aging versus immortality

Human beings and members of other species, especially animals, age and die. Fungi, too, can age. In contrast, many species can be considered immortal: for example, bacteria fission to produce daughter cells, strawberry plants grow runners to produce clones of themselves, and animals in the genus Hydra have a regenerative ability by which they avoid dying of old age.
Early life forms on Earth, starting at least 3.7 billion years ago, were single-celled organisms. Such organisms multiply by fission into daughter cells; thus do not age and are innately immortal.
Aging and mortality of the individual organism became possible with the evolution of sexual reproduction, 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. 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.
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, and specific stem cells such as germ cells. In artificial cloning, adult cells can be rejuvenated to embryonic status and then used to grow a new tissue or animal without aging. Normal human cells however die after about 50 cell divisions in laboratory culture.

Effects

A number of characteristic aging symptoms are experienced by a majority or by a significant proportion of humans during their lifetimes.
Dementia becomes more common with age. 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. 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 aging, but not semantic memory or general knowledge such as vocabulary definitions, which typically increases or remains steady until late adulthood . 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. 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.
Age can result in visual impairment, whereby non-verbal communication is reduced, 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. Macular degeneration causes vision loss and increases with age, affecting nearly 12% of those above the age of 80. This degeneration is caused by systemic changes in the circulation of waste products and by growth of abnormal vessels around the retina.
A distinction can be made between "proximal aging" and "distal aging".
Aging is among the greatest known risk factors for most human diseases. 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%.

Biological basis

At present, researchers are only just beginning to understand the biological basis of aging even in relatively simple and short-lived organisms such as yeast. Less still is known of mammalian aging, in part due to the much longer lives of even small mammals such as the mouse. A model organism for studying of aging 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. Most known mutations and RNA interference targets that extend lifespan were first discovered in C. elegans.
The factors proposed to influence biological aging fall into two main categories, programmed and damage-related. Programmed factors follow a biological timetable, perhaps one that might be a continuation of the one that regulates childhood growth and development. This regulation would depend on changes in gene expression that affect the systems responsible for maintenance, repair and defense responses. Damage-related factors include internal and environmental assaults to living organisms that induce cumulative damage at various levels. A third, novel, concept is that aging is mediated by vicious cycles.
In a detailed review, Lopez-Otin and colleagues, who discuss aging through the lens of the damage theory, propose nine metabolic "hallmarks" of aging in various organisms but especially mammals:
There are three main metabolic pathways which can influence the rate of aging, discussed below:
It is likely that most of these pathways affect aging separately, because targeting them simultaneously leads to additive increases in lifespan.

Programmed factors

The rate of aging 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. The oldest animals known so far are 15,000-year-old Antarctic sponges, 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 or 5067 years, invertebrates like the hard clam at 508 years, the Greenland shark at 400 years, various deep-sea tube worms at over 300 years, fish like the sturgeon and the rockfish, and the sea anemone and lobster. Such organisms are sometimes said to exhibit negligible senescence. 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. Studies by Becca Levy, an associate professor of epidemiology and psychology at the Yale School of Public Health, have found that positive beliefs about aging may also increase life span.

Lifestyle

substantially affects lifespan in many animals, including the ability to delay or prevent many age-related diseases. Typically, this involves caloric intake of 60–70% of what an ad libitum animal would consume, while still maintaining proper nutrient intake. In rodents, this has been shown to increase lifespan by up to 50%; similar effects occur for yeast and Drosophila. No lifespan data exist for humans on a calorie-restricted diet, but several reports support protection from age-related diseases. 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, the second study, by the National Institute on Aging, found no effects of caloric restriction on longevity. 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, and the monkeys have different origins, initially suggesting that genetics and dietary composition, not merely a decrease in calories, are factors in longevity. 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. 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.
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. 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.
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. Dietary protein restriction not only inhibits mTOR activity but also IGF-1, two mechanisms implicated in aging. Specifically, reducing leucine intake is sufficient to inhibit mTOR activity, achievable through reducing animal food consumption.
The Mediterranean diet is credited with lowering the risk of heart disease and early death. 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.
The amount of sleep has an impact on mortality. People who live the longest report sleeping for six to seven hours each night. Lack of sleep more than doubles the risk of death from cardiovascular disease, but too much sleep is associated with a doubling of the risk of death, though not primarily from cardiovascular disease. 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. 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, afternoon naps are uncommon, and insomnia is very rare.
Physical exercise may increase life expectancy. People who participate in moderate to high levels of physical exercise have a lower mortality rate compared to individuals who are not physically active. Moderate levels of exercise have been correlated with preventing aging and improving quality of life by reducing inflammatory potential. The majority of the benefits from exercise are achieved with around 3500 metabolic equivalent minutes per week. 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.
Avoidance of chronic stress is associated with a slower loss of telomeres in most but not all studies, and with decreased cortisol levels. A chronically high cortisol level compromises the immune system, causes cardiac damage/arterosclerosis and is associated with facial aging, and the latter in turn is a marker for increased morbidity and mortality. A meta-analysis shows that loneliness carries a higher mortality risk than smoking. Stress can be countered by social connection, spirituality, and married life, all of which are associated with longevity.

Medical intervention

The following drugs and interventions have been shown to slow or reverse the biological effects of aging 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.
, metformin was under study for its potential effect on slowing aging in the worm C.elegans and the cricket. Its effect on otherwise healthy humans is unknown.
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. 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. Rapamycin has subsequently been shown to extend mouse lifespan in several separate experiments, and is now being tested for this purpose in nonhuman primates.
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. " offers the possibility that normal human aging 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.
Most known genetic interventions in C. elegans increase lifespan by 1.5 to 2.5-fold., 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 aging 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.

Research projects and prizes

Some research effort is directed to slow aging and extend healthy lifespan.
In 1993, the Established populations for epidemiologic studies of the elderly, 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 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 programme aims to address this by conducting parallel experiments at three internationally recognised mouse aging-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, SENS Research Foundation, and Science for Life Extension in Russia, declared stopping or delaying aging as their goal.
Prizes for extending lifespan and slowing aging 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.

Society and culture

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, 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 aging may be distinguished from "social aging" and "biological aging".
Ageism cost the United States $63 billion in one year according to a Yale School of Public Health study. In a UNFPA report about aging 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". 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". Older people's music participation contributes to the maintenance of interpersonal relationships and promoting successful aging. At the same time, older persons can make contributions to society including caregiving and volunteering. For example, "A study of Bolivian migrants who 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."

Economics

Population aging is the increase in the number and proportion of older people in society. Population aging has three possible causes: migration, longer life expectancy and decreased birth rate. Aging has a significant impact on society. Young people tend to have fewer legal privileges, 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.
In the 21st century, one of the most significant population trends is aging. Currently, over 11% of the world's current population are people aged 60 and older and the United Nations Population Fund estimates that by 2050 that number will rise to approximately 22%. Aging 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. Aging 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".
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. 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.
Among the most urgent concerns of older persons worldwide is income security. This poses challenges for governments with aging 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."
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".
It has been argued that population aging has undermined economic development. 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."
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 aging.

Sociology

In the field of sociology and mental health, aging is seen in five different views: aging as maturity, aging as decline, aging as a life-cycle event, aging as generation, and aging as survival. Positive correlates with aging often include economics, employment, marriage, children, education, and sense of control, as well as many others, being acknowledged that resources and reserves can influence aging differently. The social science of aging 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. As cyborgs currently are on the rise some theorists argue there is a need to develop new definitions of aging and for instance a bio-techno-social definition of aging has been suggested.
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. 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. 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.

Health care demand

With age inevitable biological changes occur that increase the risk of illness and disability. UNFPA states that,
"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 aging 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 aging 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 aging 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.
It has been estimated that population aging 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.

Self-perception of aging

The beauty standards are constantly evolving over decades due to increased perception of esthetics. Because of that, the cosmeceutical industry is expanding and gradually becoming a part of many people's personal care routine. Cosmeceutical is currently the fastest growing beauty industry, with more than $42 billion in 2018. The demand for cosmeceutical is growing, especially in Asia. Korea is currently in the forefront of research and development in creating the newest cosmeceutical products with antiaging and antimelanogenic effects including ingredients such as snail secretions, botanical extract, green tea and red ginseng.
Cryptomphalus aspersa secretion has been found to have antioxidant properties, increase skin cell proliferation, as well as increasing extracellular protein such as collagen and fibronectin.
Positive self-perception of health has been correlated with higher well-being and reduced mortality in the elderly. 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 this relationship is not universal across all studies and may only be true in some circumstances.
As people age, subjective health remains relatively stable, even though objective health worsens. In fact, perceived health improves with age when objective health is controlled in the equation. This phenomenon is known as the "paradox of aging". This may be a result of social comparison; for instance, the older people get, the more they may consider themselves in better health than their same-aged peers. Elderly people often associate their functional and physical decline with the normal aging process.

Successful aging

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

Cultural references

The ancient Greek dramatist Euripides 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 describes human lifespan as inherently limited and makes a comparison with the innate immortality that a felled tree may have when undergoing vegetative regeneration.