Ageing

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Ageing (or aging in American English) is the process of becoming older. The term refers mainly to humans, many other animals, and fungi, whereas for example, bacteria, perennial plants and some simple animals are potentially biologically immortal. [1] In a broader sense, ageing can refer to single cells within an organism which have ceased dividing, or to the population of a species. [2]

Contents

In humans, ageing represents the accumulation of changes in a human being over time and can encompass physical, psychological, and social changes. [3] [4] Reaction time, for example, may slow with age, while memories and general knowledge typically increase. Ageing is associated with increased risk of cancer, Alzheimer's disease, diabetes, cardiovascular disease, increased mental health risks, and many more. [5] [6] Of the roughly 150,000 people who die each day across the globe, about two-thirds die from age-related causes. [7] Certain lifestyle choices and socioeconomic conditions have been linked to ageing. [8]

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 the internal processes (epigenetic maintenance such as DNA methylation) [9] inherently may cause ageing. Programmed ageing should not be confused with programmed cell death (apoptosis).

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. [10] 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, [11] were single-celled organisms. Such organisms (Prokaryotes, Protozoans, algae) multiply by fission into daughter cells; thus single celled organisms have been thought to not age and to be potentially immortal under favorable conditions. [12] [13] However, evidence has been reported that aging leading to death occurs in the single-cell bacterium Escherichia coli, an organism that reproduces by morphologically symmetrical division. [14] Evidence of aging has also been reported for the bacterium Caulobacter crescintus. [15] and the single cell yeast Saccharomyces cerevisiae. [16] [17]

Ageing and mortality of the individual organism became more evident with the evolution of eukaryotic sexual reproduction, [18] 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. [18] 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. [14]

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, [19] and specific stem cells such as germ cells (producing ova and spermatozoa). [20] In artificial cloning, adult cells can be rejuvenated to embryonic status and then used to grow a new tissue or animal without ageing. [21] Normal human cells however die after about 50 cell divisions in laboratory culture (the Hayflick Limit, discovered by Leonard Hayflick in 1961). [19]

Symptoms

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 Alzheimer's disease brain comparison.jpg
Comparison of a normal aged brain (left) and a brain affected by Alzheimer's disease

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. [51] About 3% of people between the ages of 65 and 74, 19% of those between 75 and 84, and nearly half of those over 85 years old have dementia. [52] 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. These typically increase or remain steady until late adulthood [53] (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 human lifespan, dropping suddenly only as people near the end of their lives. Individual variations in the rate of cognitive decline may therefore be explained in terms of people having different lengths of life. [54] 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. [55] [56]

Age can result in visual impairment, whereby non-verbal communication is reduced, [57] which can lead to isolation and possible depression. Older adults, however, may not experience depression as much as younger adults, and were paradoxically found to have improved mood, despite declining physical health. [58] Macular degeneration causes vision loss and increases with age, affecting nearly 12% of those above the age of 80. [59] This degeneration is caused by systemic changes in the circulation of waste products and by the growth of abnormal vessels around the retina. [60]

Other visual diseases that often appear with age are cataracts and glaucoma. A cataract occurs when the lens of the eye becomes cloudy, making vision blurry; it eventually causes blindness if untreated. [61] 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. [62] Glaucoma usually develops over time, but there are variations to glaucoma, and some have a sudden onset. There are a few procedures for glaucoma, but there is no cure or fix for the damage, once it has occurred. Prevention is the best measure in the case of glaucoma. [62]

In addition to physical symptoms, aging can also cause a number of mental health issues as older adults deal with challenges such as the death of loved ones, retirement and loss of purpose, as well as their own health issues. Some warning signs are: changes in mood or energy, changes in sleep or eating habits, pain, sadness, unhealthy coping mechanisms such as smoking, suicidal ideations, and others. Older adults are more prone to social isolation as well, which can further increase the risk for physical and mental conditions such as anxiety, depression, and cognitive decline.

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). [54]

Ageing 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. [63] In industrialized nations, the proportion is higher, reaching 90%. [63] [64] [65]

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

In the 21st century, researchers are only beginning to investigate the biological basis of ageing even in relatively simple and short-lived organisms, such as yeast. [66] Little 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 having a short lifespan of 2–3 weeks enabling genetic manipulations or suppression of gene activity with RNA interference, and other factors. [67] Most known mutations and RNA interference targets that extend lifespan were first discovered in C. elegans. [68]

The factors proposed to influence biological ageing fall into two main categories, programmed and error-related. [69] Programmed factors follow a biological timetable that might be a continuation of inherent mechanisms that regulate childhood growth and development. [69] This regulation would depend on changes in gene expression that affect the systems responsible for maintenance, repair and defense responses. [69] Factors causing errors or damage include internal and environmental events that induce cumulative deterioration in one or more organs. [69]

Molecular and cellular hallmarks of ageing

One 2013 review assessed ageing through the lens of the damage theory, proposing nine metabolic "hallmarks" of ageing in various organisms but especially mammals: [70]

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. [74]

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. [75] The oldest animals known so far are 15,000-year-old Antarctic sponges, [76] 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 [77] or 5067 years, [76] invertebrates like the hard clam (known as quahog in New England) at 508 years, [78] the Greenland shark at 400 years, [79] various deep-sea tube worms at over 300 years, [80] fish like the sturgeon and the rockfish, and the sea anemone [81] and lobster. [82] [83] Such organisms are sometimes said to exhibit negligible senescence. [84] The genetic aspect has also been demonstrated in studies of human centenarians.

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). [18] The biological mechanisms which regulate lifespan probably evolved with the first multicellular organisms more than a billion years ago. [68] 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. [85]

Research

Diet

The Mediterranean diet is credited with lowering the risk of heart disease and early death. [106] [107] The major contributors to mortality risk reduction appear to be a higher consumption of vegetables, fish, fruits, nuts and monounsaturated fatty acids, such as by consuming olive oil. [108]

As of 2021, there is insufficient clinical evidence that calorie restriction or any dietary practice affects the process of ageing. [109]

Exercise

People who participate in moderate to high levels of physical exercise have a lower mortality rate compared to individuals who are not physically active. [110] The majority of the benefits from exercise are achieved with around 3500 metabolic equivalent (MET) minutes per week. [111] 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. [111]

Exercise has also been found to be an effective measure to treat declines in neuromuscular function due to age. [112] A meta-analysis found that resistance training with elastic bands or kettlebells provided significant improvements to grip strength, gait speed, and skeletal muscle mass in patients with sarcopenia. [112] Furthermore, another analysis found that the positive effects of resistance exercise on strength, muscle mass, and motor coordination reduce the risk of falls in the elderly, which is a key factor for living a longer and healthier life. [113] In terms of programming, there is no one-size-fits-all approach. [112] [113] General recommendations for improvements to gait speed, strength, and muscle size for reduced fall risk are resistance training programs with two to three 40-60 minute workouts per week, consisting of 1-2 sets of 5-8 repetitions of 2-3 different exercises for each major muscle group, but individual considerations must be taken due to differences in health status, motivation, and accessibility to exercise facilities. [112] [113] [112] [113]

There is also evidence to suggest that exercise of any type may mitigate the degradation of the neuromuscular junction (NMJ) that occurs with age. [114] Current evidence suggests that aerobic exercise causes the most hypertrophy of the NMJ, although resistance training is still somewhat effective. [114] However, further evidence is necessary to identify optimal training protocols for NMJ function and to further understand how exercise affects the mechanisms that cause NMJ degradation. [114]

Social factors

A meta-analysis showed that loneliness carries a higher mortality risk than smoking. [115]

Society and culture

A grandmother and her grandchild Nowruz 2017 in Bisaran, Kurdistan province.jpg
A grandmother and her grandchild

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. (The most notable exception East Asian age reckoning is becoming less common, particularly in official contexts.) Arbitrary divisions set to mark periods of life may include juvenile (from infancy through childhood, preadolescence, and adolescence), early adulthood, middle adulthood, and late adulthood. Informal[ citation needed ] terms include "tweens", "teenagers", "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 organization 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). [116]

Ageism cost the United States $63 billion in one year according to a Yale School of Public Health study. [117] 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". [118] 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". [118] Older people's music participation contributes to the maintenance of interpersonal relationships and promoting successful ageing. [119] 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." [118]

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. [120]

In the 21st century, one of the most significant population trends is ageing. [121] 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%. [118] 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". [122]

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. [123] 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. [124] 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. [124] [ needs update ]

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 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." [118]

The global economic crisis has increased financial pressure to ensure economic security and access to health care in old age. 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". [118]

It has been argued that population ageing has undermined economic development [125] 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." [118]

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. [126]

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. [127] 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. [128] As cyborgs currently are on the rise [129] 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. [130]

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. [131] 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. [132] 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. [133]

Health care demand

With age inevitable biological changes occur that increase the risk of illness and disability. UNFPA states that: [122]

"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 organized under four headings: improve system performance; redesign service delivery; support informal caregivers; and shift demographic parameters. [134]

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. [135] 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. [136]

Self-perception

Beauty standards have evolved over time, and as scientific research in cosmeceuticals, cosmetic products seen to have medicinal benefits like anti-ageing creams, 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. [137]

The increase in demand for cosmeceuticals has led scientists to find ingredients for these products in unorthodox places. For example, the secretion of cryptomphalus aspersa (or brown garden snail) has been found to have antioxidant properties, increase skin cell proliferation, and increase extracellular proteins such as collagen and fibronectin (important proteins for cell proliferation). [138] Another substance used to prevent the physical manifestations of ageing is onobotulinumtoxinA, the toxin injected for Botox. [139]

In some cultures, old age is celebrated and honoured. In Korea, for example, a special party called hwangap is held to celebrate and congratulate an individual for turning 60 years old. [140] In China, respect for elderly is often the basis for how a community is organized and has been at the foundation of Chinese culture and morality for thousands of years. Older people are respected for their wisdom and most important decisions have traditionally not been made without consulting them. This is a similar case for most Asian countries such as the Philippines, Thailand, Vietnam, Singapore, etc.

Positive self-perceptions of ageing are associated with better mental and physical health and well-being. [141] Positive self-perception of health has been correlated with higher well-being and reduced mortality among the elderly. [142] [143] 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. [144] This finding is generally stronger for men than women, [143] though this relationship is not universal across all studies and may only be true in some circumstances. [144]

As people age, subjective health remains relatively stable, even though objective health worsens. [145] In fact, perceived health improves with age when objective health is controlled in the equation. [146] This phenomenon is known as the "paradox of ageing". This may be a result of social comparison; [147] for instance, the older people get, the more they may consider themselves in better health than their same-aged peers. [148] Elderly people often associate their functional and physical decline with the normal ageing process. [149] [150]

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. [151] [152] [153] These suits create the feelings of the effects of ageing 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 ageing, or those who work with the elderly, such as nurses or care centre staff.

Design is another field that could benefit from the empathy these suits may cause. [151] [153] 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.

Healthy ageing

The healthy ageing framework, proposed by the World Health Organation [154] operationalizes health as functional ability, which results from the interactions of intrinsic capacity and the environments.

Intrinsic capacity

Intrinsic capacity is a construct encompassing people's physical and mental abilities which can be drawn upon during ageing. [155] Intrinsic capacity comprises the domains of: cognition, locomotion, vitality/nutrition, psychological and sensory (visual and hearing). [156]

A recent study found four "profiles" or "statuses" of intrinsic capacity among older adults, namely high IC (43% at baseline), low deterioration with impaired locomotion (17%), high deterioration without cognitive impairment (22%) and high deterioration with cognitive impairment (18%). Over half of the study sample remained in the same status at baseline and follow-up (61%). Around one-fourth of participants transitioned from the high IC to the low deterioration status, and only 3% of the participants improved their status. Interestingly, the probability of improvement was observed in the status of high deterioration. Participants in the latent statuses of low and high levels of deterioration had a significantly higher risk of frailty, disability and dementia than their high IC counterparts. [157]

Successful aging

The concept of successful aging can be traced back to the 1950s and was popularized in the 1980s. Traditional definitions of successful aging have emphasized absence of physical and cognitive disabilities. [158] In their 1987 article, Rowe and Kahn characterized successful aging as involving three components: a) freedom from disease and disability, b) high cognitive and physical functioning, and c) social and productive engagement. [159] The study cited previous was also done back in 1987 and therefore, these factors associated with successful aging have probably been changed. With the current knowledge, scientists started to focus on learning about the effect spirituality in successful aging. There are some differences in cultures as to 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 aging changes. [160]

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 the human lifespan as inherently limited and makes a comparison with the innate immortality that a felled tree may have when undergoing vegetative regeneration:

A man's days are numbered. You know the number of his months. He cannot live longer than the time You have set. So now look away from him that he may rest, until he has lived the time set for him like a man paid to work. For there is hope for a tree, when it is cut down, that it will grow again, and that its branches will not stop growing. [161]

See also

Related Research Articles

Senescence or biological aging is the gradual deterioration of functional characteristics in living organisms. Whole organism senescence involves an increase in death rates or a decrease in fecundity with increasing age, at least in the later part of an organism's life cycle. However, the resulting effects of senescence can be delayed. The 1934 discovery that calorie restriction can extend lifespans by 50% in rats, the existence of species having negligible senescence, and the existence of potentially immortal organisms such as members of the genus Hydra have motivated research into delaying senescence and thus age-related diseases. Rare human mutations can cause accelerated aging diseases.

<span class="mw-page-title-main">Life extension</span> Concept of extending human lifespan by improvements in medicine or biotechnology

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 biological limit of around 125 years. Several researchers in the area, along with "life extensionists", "immortalists", or "longevists", postulate that future breakthroughs in tissue rejuvenation, stem cells, regenerative medicine, molecular repair, gene therapy, pharmaceuticals, and organ replacement will eventually enable humans to have indefinite lifespans through complete rejuvenation to a healthy youthful condition (agerasia). The ethical ramifications, if life extension becomes a possibility, are debated by bioethicists.

<span class="mw-page-title-main">Longevity</span> Longer than typical lifespan, especially of humans

Longevity may refer to especially long-lived members of a population, whereas life expectancy is defined statistically as the average number of years remaining at a given age. For example, a population's life expectancy at birth is the same as the average age at death for all people born in the same year.

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.

<span class="mw-page-title-main">Gerontology</span> Study of the social, psychological and biological aspects of aging

Gerontology is the study of the social, cultural, psychological, cognitive, and biological aspects of aging. The word was coined by Ilya Ilyich Mechnikov in 1903, from the Greek γέρων (gérōn), meaning "old man", and -λογία (-logía), meaning "study of". The field is distinguished from geriatrics, which is the branch of medicine that specializes in the treatment of existing disease in older adults. Gerontologists include researchers and practitioners in the fields of biology, nursing, medicine, criminology, dentistry, social work, physical and occupational therapy, psychology, psychiatry, sociology, economics, political science, architecture, geography, pharmacy, public health, housing, and anthropology.

The free radical theory of aging 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.

<span class="mw-page-title-main">Biogerontology</span> 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 journal 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.

<span class="mw-page-title-main">Sarcopenia</span> Muscle loss due to ageing or immobility

Sarcopenia is a type of muscle loss that occurs with aging and/or immobility. It is characterized by the degenerative loss of skeletal muscle mass, quality, and strength. The rate of muscle loss is dependent on exercise level, co-morbidities, nutrition and other factors. The muscle loss is related to changes in muscle synthesis signalling pathways. It is distinct from cachexia, in which muscle is degraded through cytokine-mediated degradation, although the two conditions may co-exist. Sarcopenia is considered a component of frailty syndrome. Sarcopenia can lead to reduced quality of life, falls, fracture, and disability.

Enquiry into the evolution of ageing, or aging, aims to explain why a detrimental process such as ageing would evolve, and why there is so much variability in the lifespans of organisms. The classical theories of evolution suggest that environmental factors, such as predation, accidents, disease, and/or 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.

<span class="mw-page-title-main">Eternal youth</span> 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.

<span class="mw-page-title-main">Frailty syndrome</span> Weakness in elderly person

Frailty is a common and clinically significant grouping of symptoms that occurs in aging and older adults. These symptoms can include decreased physical abilities such as walking, excessive fatigue, and weight and muscle loss leading to declined physical status. In addition, frailty encompasses a decline in both overall physical function and physiologic reserve of organ systems resulting in worse health outcomes for this population. This syndrome is associated with increased risk of heart disease, falls, hospitalization, and death. In addition, it has been shown that adults living with frailty face more anxiety and depression symptoms than those who do not. The presence of frailty varies based on the assessment technique, however it is estimated that 4-16% of the population over 65 years old is living with frailty.

<span class="mw-page-title-main">Aging-associated diseases</span> Type of disease

An aging-associated disease is a disease that is most often seen with increasing frequency with increasing senescence. They are essentially complications of senescence, distinguished from the aging process itself because all adult animals age but not all adult animals experience all age-associated diseases. The term does not refer to age-specific diseases, such as the childhood diseases chicken pox and measles, only diseases of the elderly. They are also not accelerated aging diseases, all of which are genetic disorders.

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.

<span class="mw-page-title-main">Antagonistic pleiotropy hypothesis</span> Proposed evolutionary explanation for senescence

The antagonistic pleiotropy hypothesis (APT) is a theory in evolutionary biology that suggests certain genes may confer beneficial effects early in an organism's life, enhancing reproductive success, while also causing detrimental effects later in life, contributing to the aging process.

<span class="mw-page-title-main">Negligible senescence</span> Organisms that do not exhibit evidence of biological aging

Negligible senescence is a term coined by biogerontologist Caleb Finch to denote organisms that do not exhibit evidence of biological aging (senescence), such as measurable reductions in their reproductive capability, measurable functional decline, or rising death rates with age. There are many species where scientists have seen no increase in mortality after maturity. This may mean that the lifespan of the organism is so long that researchers' subjects have not yet lived up to the time when a measure of the species' longevity can be made. Turtles, for example, were once thought to lack senescence, but more extensive observations have found evidence of decreasing fitness with age.

<span class="mw-page-title-main">Biomarkers of aging</span> Type of biomarkers

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.

<span class="mw-page-title-main">Genetics of aging</span> 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.

<span class="mw-page-title-main">Mitochondrial theory of ageing</span> Theory of ageing

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

Aging is characterized by a progressive loss of physiological integrity, leading to impaired function and increased vulnerability to death. 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 listed 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 into senescence or biological aging, including the research and development of life extension methods, brain aging delay methods and rejuvenation.

References

  1. Smadent.com (2021). "Age Calculator". Smadent. 2 (1). Retrieved 12 February 2021.
  2. Liochev SI (December 2015). "Which Is the Most Significant Cause of Aging?". Antioxidants. 4 (4): 793–810. doi: 10.3390/antiox4040793 . PMC   4712935 . PMID   26783959.
  3. "Understanding the Dynamics of the Aging Process". National Institute on Aging. Retrieved 19 May 2021.
  4. Prakash IJ (October 1997). "Women & ageing". The Indian Journal of Medical Research. 106: 396–408. PMID   9361474.
  5. Ahmed AS, Sheng MH, Wasnik S, Baylink DJ, Lau KW (February 2017). "Effect of aging on stem cells". World Journal of Experimental Medicine. 7 (1): 1–10. doi: 10.5493/wjem.v7.i1.1 . PMC   5316899 . PMID   28261550.
  6. Renstrom, Joelle (2 March 2020). "Is Aging a Disease?". Slate Magazine. Retrieved 16 January 2022.
  7. Grey, Aubrey D. N. J. de (21 December 2007). "Life Span Extension Research and Public Debate: Societal Considerations". Studies in Ethics, Law, and Technology. 1 (1). doi:10.2202/1941-6008.1011. ISSN   1941-6008.
  8. Salvestrini V, Sell C, Lorenzini A (3 May 2019). "Obesity May Accelerate the Aging Process". Frontiers in Endocrinology. 10: 266. doi: 10.3389/fendo.2019.00266 . PMC   6509231 . PMID   31130916.
  9. Miller, Freda D.; Kaplan, David R. (February 2007). "To Die or Not to Die: Neurons and p63". Cell Cycle. 6 (3): 312–317. doi:10.4161/cc.6.3.3795. PMID   17264677. S2CID   24939720.
  10. Mortimer RK, Johnston JR (June 1959). "Life span of individual yeast cells". Nature. 183 (4677): 1751–2. Bibcode:1959Natur.183.1751M. doi:10.1038/1831751a0. hdl: 2027/mdp.39015078535278 . PMID   13666896. S2CID   4149521.
  11. Nutman AP, Bennett VC, Friend CR, Van Kranendonk MJ, Chivas AR (September 2016). "Rapid emergence of life shown by discovery of 3,700-million-year-old microbial structures". Nature (Submitted manuscript). 537 (7621): 535–538. Bibcode:2016Natur.537..535N. doi:10.1038/nature19355. PMID   27580034. S2CID   205250494.
  12. Rose MR (1991). Evolutionary Biology of Aging. New York: Oxford University Press.
  13. Partridge L, Barton NH (March 1993). "Optimality, mutation and the evolution of aging". Nature. 362 (6418): 305–11. Bibcode:1993Natur.362..305P. doi:10.1038/362305a0. PMID   8455716. S2CID   4330925.
  14. 1 2 Stewart EJ, Madden R, Paul G, Taddei F (February 2005). "Aging and death in an organism that reproduces by morphologically symmetric division". PLOS Biol. 3 (2): e45. doi: 10.1371/journal.pbio.0030045 . PMC   546039 . PMID   15685293.
  15. Ackermann M, Stearns SC, Jenal U (June 2003). "Senescence in a bacterium with asymmetric division". Science. 300 (5627): 1920. doi:10.1126/science.1083532. PMID   12817142.
  16. Sinclair DA (April 2002). "Paradigms and pitfalls of yeast longevity research". Mech Ageing Dev. 123 (8): 857–67. doi:10.1016/s0047-6374(02)00023-4. PMID   12044934.
  17. Jazwinski SM (2002). "Growing old: metabolic control and yeast aging". Annu Rev Microbiol. 56: 769–92. doi:10.1146/annurev.micro.56.012302.160830. PMID   12213938.
  18. 1 2 3 Williams GC (1957). "Pleiotropy, Natural Selection, and the Evolution of Senescence". Evolution. 11 (4): 398–411. doi:10.2307/2406060. JSTOR   2406060.
  19. 1 2 Pereira-Smith OM, Ning Y (1992). "Molecular genetic studies of cellular senescence". Experimental Gerontology. 27 (5–6): 519–22. doi:10.1016/0531-5565(92)90006-L. PMID   1426085. S2CID   27839420.
  20. Forster P, Hohoff C, Dunkelmann B, Schürenkamp M, Pfeiffer H, Neuhuber F, Brinkmann B (March 2015). "Elevated germline mutation rate in teenage fathers". Proceedings. Biological Sciences. 282 (1803): 20142898. doi:10.1098/rspb.2014.2898. PMC   4345458 . PMID   25694621.
  21. Wakayama S, Kohda T, Obokata H, Tokoro M, Li C, Terashita Y, et al. (March 2013). "Successful serial recloning in the mouse over multiple generations". Cell Stem Cell. 12 (3): 293–7. doi: 10.1016/j.stem.2013.01.005 . PMID   23472871.
  22. 1 2 Rodríguez Valiente A, Trinidad A, García Berrocal JR, Górriz C, Ramírez Camacho R (August 2014). "Extended high-frequency (9–20 kHz) audiometry reference thresholds in 645 healthy subjects". International Journal of Audiology. 53 (8): 531–45. doi:10.3109/14992027.2014.893375. PMID   24749665. S2CID   30960789.
  23. Education.com (23 May 2013). "Sonic Science: The High-Frequency Hearing Test". Scientific American . Retrieved 25 May 2017.
  24. Moss S (July 2013). "Big ears: they really do grow as we age". The Guardian. MeshID:D000375; OMIM:502000. Retrieved 9 September 2016.
  25. 1 2 Gerasimov IG, Ignatov DY (2004). "Age Dynamics of Body Mass and Human Lifespan". Journal of Evolutionary Biochemistry and Physiology. 40 (3): 343–349. doi:10.1023/B:JOEY.0000042639.72529.e1. S2CID   9070790.
  26. Thurstan SA, Gibbs NK, Langton AK, Griffiths CE, Watson RE, Sherratt MJ (April 2012). "Chemical consequences of cutaneous photoageing". Chemistry Central Journal. 6 (1): 34. doi: 10.1186/1752-153X-6-34 . PMC   3410765 . PMID   22534143.
  27. "Infertility: Overview". InformedHealth.org. Cologne: Institute for Quality and Efficiency in Health Care. 25 March 2015 via NCBI Bookshelf.
  28. "Facts About Presbyopia". National Eye Institute. Archived from the original on 4 October 2016. Retrieved 11 September 2016.
  29. Weale RA (2003). "Epidemiology of refractive errors and presbyopia". Survey of Ophthalmology. 48 (5): 515–43. doi:10.1016/S0039-6257(03)00086-9. PMID   14499819.
  30. 1 2 Truscott RJ (February 2009). "Presbyopia. Emerging from a blur towards an understanding of the molecular basis for this most common eye condition". Experimental Eye Research. 88 (2): 241–7. doi:10.1016/j.exer.2008.07.003. PMID   18675268.
  31. Pathai S, Shiels PG, Lawn SD, Cook C, Gilbert C (March 2013). "The eye as a model of ageing in translational research—molecular, epigenetic and clinical aspects". Ageing Research Reviews. 12 (2): 490–508. doi:10.1016/j.arr.2012.11.002. PMID   23274270. S2CID   26015190.
  32. Pandhi D, Khanna D (2013). "Premature graying of hair". Indian Journal of Dermatology, Venereology and Leprology. 79 (5): 641–53. doi: 10.4103/0378-6323.116733 . PMID   23974581.
  33. Hamilton JB (March 1951). "Patterned loss of hair in man; types and incidence". Annals of the New York Academy of Sciences. 53 (3): 708–28. Bibcode:1951NYASA..53..708H. doi:10.1111/j.1749-6632.1951.tb31971.x. PMID   14819896. S2CID   32685699.
  34. Vary JC (November 2015). "Selected Disorders of Skin Appendages--Acne, Alopecia, Hyperhidrosis". The Medical Clinics of North America. 99 (6): 1195–211. doi:10.1016/j.mcna.2015.07.003. PMID   26476248.
  35. Morabia A, Costanza MC (December 1998). "International variability in ages at menarche, first livebirth, and menopause. World Health Organization Collaborative Study of Neoplasia and Steroid Contraceptives". American Journal of Epidemiology. 148 (12): 1195–205. doi: 10.1093/oxfordjournals.aje.a009609 . PMID   9867266.
  36. Thomas E, Peat G, Croft P (February 2014). "Defining and mapping the person with osteoarthritis for population studies and public health". Rheumatology. 53 (2): 338–45. doi:10.1093/rheumatology/ket346. PMC   3894672 . PMID   24173433.
  37. "Hearing Loss and Older Adults" (Last Updated 3 June 2016). National Institute on Deafness and Other Communication Disorders. 26 January 2016. Retrieved 11 September 2016.
  38. Rubel EW, Furrer SA, Stone JS (March 2013). "A brief history of hair cell regeneration research and speculations on the future". Hearing Research. 297: 42–51. doi:10.1016/j.heares.2012.12.014. PMC   3657556 . PMID   23321648.
  39. "Facts About Cataract". September 2015. Retrieved 14 August 2016.
  40. Fried LP, Tangen CM, Walston J, Newman AB, Hirsch C, Gottdiener J, et al. (March 2001). "Frailty in older adults: evidence for a phenotype". The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences. 56 (3): M146-56. CiteSeerX   10.1.1.456.139 . doi:10.1093/gerona/56.3.m146. PMID   11253156.
  41. Percentage derived from Table 2 in Fried et al. 2001
  42. Ryall JG, Schertzer JD, Lynch GS (August 2008). "Cellular and molecular mechanisms underlying age-related skeletal muscle wasting and weakness". Biogerontology. 9 (4): 213–28. doi:10.1007/s10522-008-9131-0. PMID   18299960. S2CID   8576449.
  43. Betik AC, Hepple RT (February 2008). "Determinants of VO2 max decline with aging: an integrated perspective". Applied Physiology, Nutrition, and Metabolism. 33 (1): 130–40. doi:10.1139/H07-174. PMID   18347663. S2CID   24468921.
  44. Ranganathan VK, Siemionow V, Sahgal V, Yue GH (November 2001). "Effects of aging on hand function". Journal of the American Geriatrics Society . 49 (11): 1478–84. doi:10.1046/j.1532-5415.2001.4911240.x. PMID   11890586. S2CID   22988219.
  45. 1 2 Wang JC, Bennett M (July 2012). "Aging and atherosclerosis: mechanisms, functional consequences, and potential therapeutics for cellular senescence". Circulation Research. 111 (2): 245–59. doi: 10.1161/CIRCRESAHA.111.261388 . PMID   22773427.
  46. Herrington W, Lacey B, Sherliker P, Armitage J, Lewington S (February 2016). "Epidemiology of Atherosclerosis and the Potential to Reduce the Global Burden of Atherothrombotic Disease". Circulation Research. 118 (4): 535–46. doi: 10.1161/CIRCRESAHA.115.307611 . PMID   26892956.
  47. "The top 10 causes of death". WHO. 9 December 2020. Retrieved 11 March 2021.
  48. "Does Human Life Span Really Have a Limit?". WebMD. 28 June 2018.
  49. Zimmer C (5 October 2016). "What's the Longest Humans Can Live? 115 Years, New Study Says". The New York Times . Retrieved 6 October 2016.
  50. Dong X, Milholland B, Vijg J (October 2016). "Evidence for a limit to human lifespan". Nature. 538 (7624): 257–259. Bibcode:2016Natur.538..257D. doi:10.1038/nature19793. PMID   27706136. S2CID   3623127.
  51. Larson EB, Yaffe K, Langa KM (December 2013). "New insights into the dementia epidemic". The New England Journal of Medicine. 369 (24): 2275–7. doi:10.1056/nejmp1311405. PMC   4130738 . PMID   24283198.
  52. Umphred D (2012). Neurological rehabilitation (6th ed.). St. Louis, MO: Elsevier Mosby. p. 838. ISBN   978-0-323-07586-2.
  53. Schaie KW (2005). Developmental Influences on Adult Intelligence. doi:10.1093/acprof:oso/9780195156737.001.0001. ISBN   978-0-19-515673-7.[ page needed ]
  54. 1 2 Stuart-Hamilton I (2006). The Psychology of Ageing: An Introduction. London: Jessica Kingsley Publishers. ISBN   978-1-84310-426-1.
  55. Marner L, Nyengaard JR, Tang Y, Pakkenberg B (July 2003). "Marked loss of myelinated nerve fibers in the human brain with age". The Journal of Comparative Neurology. 462 (2): 144–52. doi:10.1002/cne.10714. PMID   12794739. S2CID   35293796.
  56. Peters A (1 January 2007). "The Effects of Normal Aging on Nerve Fibers and Neuroglia in the Central Nervous System". In Riddle DR (ed.). Brain Aging: Models, Methods, and Mechanisms. Frontiers in Neuroscience. CRC Press/Taylor & Francis. ISBN   978-0-8493-3818-2. PMID   21204349.
  57. Worrall L, Hickson LM (2003). "Theoretical foundations of communication disability in aging". In Worrall L, Hickson LM (eds.). Communication disability in aging: from prevention to intervention. Clifton Park, NY: Delmar Learning. pp. 32–33.
  58. Lys R, Belanger E, Phillips SP (April 2019). "Improved mood despite worsening physical health in older adults: Findings from the International Mobility in Aging Study (IMIAS)". PLOS ONE. 14 (4): e0214988. Bibcode:2019PLoSO..1414988L. doi: 10.1371/journal.pone.0214988 . PMC   6453471 . PMID   30958861.
  59. Mehta S (September 2015). "Age-Related Macular Degeneration". Primary Care. 42 (3): 377–91. doi:10.1016/j.pop.2015.05.009. PMID   26319344.
  60. Nussbaum JF, Thompson TL, Robinson JD (1989). "Barriers to conversation". In Nussbaum JF, Thompson TL, Robinson JD (eds.). Communication and aging. New York: Harper & Row. pp. 234–53.
  61. "Cataracts | National Eye Institute". www.nei.nih.gov. Retrieved 3 July 2021.
  62. 1 2 "Glaucoma | National Eye Institute". www.nei.nih.gov. Retrieved 3 July 2021.
  63. 1 2 De Grey AD (2007). "Life Span Extension Research and Public Debate: Societal Considerations". Studies in Ethics, Law, and Technology. 1. CiteSeerX   10.1.1.395.745 . doi:10.2202/1941-6008.1011. S2CID   201101995.
  64. Lopez AD, Mathers CD, Ezzati M, Jamison DT, Murray CJ (May 2006). "Global and regional burden of disease and risk factors, 2001: systematic analysis of population health data". Lancet. 367 (9524): 1747–57. doi:10.1016/S0140-6736(06)68770-9. PMID   16731270. S2CID   22609505.
  65. Brunet Lab: Molecular Mechanisms of Longevity and Age Related Diseases. Stanford.edu. Retrieved on 11 April 2012.
  66. 1 2 Janssens GE, Meinema AC, González J, et al. (December 2015). "Protein biogenesis machinery is a driver of replicative aging in yeast". eLife. 4: e08527. doi: 10.7554/eLife.08527 . PMC   4718733 . PMID   26422514.
  67. Wilkinson DS, Taylor RC, Dillin A (2012). "Analysis of Aging". In Rothman JH, Singson A (eds.). Caenorhabditis Elegans: Cell Biology and Physiology. Academic Press. pp. 353–381. ISBN   978-0-12-394620-1.
  68. 1 2 Shmookler Reis RJ, Bharill P, Tazearslan C, Ayyadevara S (October 2009). "Extreme-longevity mutations orchestrate silencing of multiple signaling pathways". Biochimica et Biophysica Acta (BBA) - General Subjects. 1790 (10): 1075–1083. doi:10.1016/j.bbagen.2009.05.011. PMC   2885961 . PMID   19465083.
  69. 1 2 3 4 5 Jin K (October 2010). "Modern Biological Theories of Aging". Aging and Disease. 1 (2): 72–74. PMC   2995895 . PMID   21132086.
  70. López-Otín C, Blasco MA, Partridge L, Serrano M, Kroemer G (June 2013). "The hallmarks of aging". Cell. 153 (6): 1194–217. doi:10.1016/j.cell.2013.05.039. PMC   3836174 . PMID   23746838.
  71. Arleo A, Bares M, Bernard JA, Bogoian HR, Bruchhage MM (July 2013). "Consensus Paper: Cerebellum and Ageing". Cerebellum. 23 (2): 802–832. doi:10.1007/s12311-023-01577-7. PMC   10776824 . PMID   37428408. S2CID   259499418.
  72. Ratiner K, Abdeen SK, Goldenberg K, Elinav E (March 2022). "Utilization of Host and Microbiome Features in Determination of Biological Aging". Microorganisms. 10 (3): 668. doi: 10.3390/microorganisms10030668 . PMC   8950177 . PMID   35336242.
  73. Berdyshev GD, Korotaev GK, Boiarskikh GV, Vaniushin BF (2008). "Molecular Biology of Aging". Cell. 96 (2). Cold Spring Harbor: 347–62. doi: 10.1016/s0092-8674(00)80567-x . ISBN   978-0-87969-824-9. PMID   9988222. S2CID   17724023.
  74. Taylor RC, Dillin A (May 2011). "Aging as an event of proteostasis collapse". Cold Spring Harbor Perspectives in Biology. 3 (5): a004440. doi:10.1101/cshperspect.a004440. PMC   3101847 . PMID   21441594.
  75. Melzer S, Lens F, Gennen J, Vanneste S, Rohde A, Beeckman T (December 2008). "Flowering-time genes modulate meristem determinacy and growth form in Arabidopsis thaliana". Nature Genetics. 40 (12): 1489–92. doi:10.1038/ng.253. PMID   18997783. S2CID   13225884.
  76. 1 2 Chesterton M (12 June 2017). "The oldest living thing on Earth". BBC News. Retrieved 16 September 2017.
  77. "Oldlist". Rocky Mountain Tree Ring Research. Retrieved 12 August 2016.
  78. Sosnowska D, Richardson C, Sonntag WE, Csiszar A, Ungvari Z, Ridgway I (December 2014). "A heart that beats for 500 years: age-related changes in cardiac proteasome activity, oxidative protein damage and expression of heat shock proteins, inflammatory factors, and mitochondrial complexes in Arctica islandica, the longest-living noncolonial animal". The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences. 69 (12): 1448–61. doi:10.1093/gerona/glt201. PMC   4271020 . PMID   24347613.
  79. Nielsen J, Hedeholm RB, Heinemeier J, Bushnell PG, Christiansen JS, Olsen J, et al. (August 2016). "Eye lens radiocarbon reveals centuries of longevity in the Greenland shark (Somniosus microcephalus)". Science. 353 (6300): 702–4. Bibcode:2016Sci...353..702N. doi:10.1126/science.aaf1703. hdl: 2022/26597 . PMID   27516602. S2CID   206647043.
  80. Durkin A, Fisher CR, Cordes EE (August 2017). "Extreme longevity in a deep-sea vestimentiferan tubeworm and its implications for the evolution of life history strategies". Die Naturwissenschaften. 104 (7–8): 63. Bibcode:2017SciNa.104...63D. doi:10.1007/s00114-017-1479-z. PMID   28689349. S2CID   11287549.
  81. Timiras, Paola S. (2003) Physiological Basis of Ageing and Geriatrics. Informa Health Care. ISBN   0-8493-0948-4. p. 26.
  82. Silverman J (5 July 2007). "Is there a 400 pound lobster out there?". howstuffworks.
  83. Wallace DF (2005). Consider the Lobster and Other Essays. Little, Brown & Company. ISBN   978-0-316-15611-0.[ page needed ]
  84. Guerin JC (June 2004). "Emerging area of aging research: long-lived animals with "negligible senescence"". Annals of the New York Academy of Sciences. 1019 (1): 518–20. Bibcode:2004NYASA1019..518G. doi:10.1196/annals.1297.096. PMID   15247078. S2CID   6418634.
  85. Sampaio-Marques, Belém; Burhans, William C.; Ludovico, Paula (2019). "Yeast at the Forefront of Research on Ageing and Age-Related Diseases". Yeasts in Biotechnology and Human Health. Progress in Molecular and Subcellular Biology. Vol. 58. pp. 217–242. doi:10.1007/978-3-030-13035-0_9. hdl: 1822/62308 . ISBN   978-3-030-13034-3. ISSN   0079-6484. PMID   30911895. S2CID   85516879.
  86. Gensler HL, Bernstein H (September 1981). "DNA damage as the primary cause of aging". The Quarterly Review of Biology. 56 (3): 279–303. doi:10.1086/412317. JSTOR   2826464. PMID   7031747. S2CID   20822805.
  87. Freitas AA, de Magalhães JP (2011). "A review and appraisal of the DNA damage theory of ageing". Mutation Research. 728 (1–2): 12–22. Bibcode:2011MRRMR.728...12F. doi:10.1016/j.mrrev.2011.05.001. PMID   21600302.
  88. Robert L, Labat-Robert J, Robert AM (August 2010). "Genetic, epigenetic and posttranslational mechanisms of aging". Biogerontology. 11 (4): 387–99. doi:10.1007/s10522-010-9262-y. PMID   20157779. S2CID   21455794.
  89. Soares JP, Cortinhas A, Bento T, Leitão JC, Collins AR, Gaivão I, Mota MP (June 2014). "Aging and DNA damage in humans: a meta-analysis study". Aging (Albany NY). 6 (6): 432–9. doi:10.18632/aging.100667. PMC   4100806 . PMID   25140379.
  90. Beerman I (January 2017). "Accumulation of DNA damage in the aged hematopoietic stem cell compartment". Semin Hematol. 54 (1): 12–18. doi:10.1053/j.seminhematol.2016.11.001. PMC   5242379 . PMID   28088982.
  91. Vlachogiannis NI, Ntouros PA, Pappa M, Kravvariti E, Kostaki EG, Fragoulis GE, Papanikolaou C, Mavroeidi D, Bournia VK, Panopoulos S, Laskari K, Arida A, Gorgoulis VG, Tektonidou MG, Paraskevis D, Sfikakis PP, Souliotis VL (April 2023). "Chronological Age and DNA Damage Accumulation in Blood Mononuclear Cells: A Linear Association in Healthy Humans after 50 Years of Age". Int J Mol Sci. 24 (8): 7148. doi: 10.3390/ijms24087148 . PMC   10138488 . PMID   37108309.
  92. Cao H, Deng B, Song T, Lian J, Xia L, Chu X, Zhang Y, Yang F, Wang C, Cai Y, Diao Y, Kapranov P (May 2024). "Genome-wide profiles of DNA damage represent highly accurate predictors of mammalian age". Aging Cell. 23 (5): e14122. doi:10.1111/acel.14122. PMC   11113270 . PMID   38391092.
  93. Strehler BL (1986). "Genetic instability as the primary cause of human aging". Experimental Gerontology. 21 (4–5): 283–319. doi:10.1016/0531-5565(86)90038-0. PMID   3545872. S2CID   34431271.
  94. Gavrilov LA, Gavrilova NA (2006). "Reliability Theory of Aging and Longevity". In Masoro EJ, Austad SN (eds.). Handbook of the Biology of Aging. San Diego, CA: Academic Press. pp. 3–42.
  95. Carroll B, Hewitt G, Korolchuk VI (2013). "Autophagy and ageing: implications for age-related neurodegenerative diseases". Essays in Biochemistry. 55: 119–31. doi:10.1042/bse0550119. PMID   24070476. S2CID   1603760.
  96. Lee JH, Kim EW, Croteau DL, Bohr VA (September 2020). "Heterochromatin: an epigenetic point of view in aging". Experimental & Molecular Medicine. 52 (9): 1466–1474. doi: 10.1038/s12276-020-00497-4 . PMC   8080806 . PMID   32887933.
  97. Tsurumi A, Li WX (July 2012). "Global heterochromatin loss: a unifying theory of aging?". Epigenetics. 7 (7): 680–8. doi:10.4161/epi.20540. PMC   3414389 . PMID   22647267.
  98. Bjorksten J, Tenhu H (1990). "The crosslinking theory of aging—added evidence". Experimental Gerontology. 25 (2): 91–5. doi:10.1016/0531-5565(90)90039-5. PMID   2115005. S2CID   19115146.
  99. Trifunovic A, Larsson NG (February 2008). "Mitochondrial dysfunction as a cause of ageing". Journal of Internal Medicine. 263 (2): 167–78. doi: 10.1111/j.1365-2796.2007.01905.x . PMID   18226094. S2CID   28396237.
  100. Harman D (November 1981). "The aging process". Proceedings of the National Academy of Sciences of the United States of America. 78 (11): 7124–8. Bibcode:1981PNAS...78.7124H. doi: 10.1073/pnas.78.11.7124 . PMC   349208 . PMID   6947277.
  101. Schulz TJ, Zarse K, Voigt A, Urban N, Birringer M, Ristow M (October 2007). "Glucose restriction extends Caenorhabditis elegans life span by inducing mitochondrial respiration and increasing oxidative stress". Cell Metabolism. 6 (4): 280–93. doi: 10.1016/j.cmet.2007.08.011 . PMID   17908557.
  102. Hamilton ML, Van Remmen H, Drake JA, Yang H, Guo ZM, Kewitt K, et al. (August 2001). "Does oxidative damage to DNA increase with age?". Proceedings of the National Academy of Sciences of the United States of America. 98 (18): 10469–74. Bibcode:2001PNAS...9810469H. doi: 10.1073/pnas.171202698 . PMC   56984 . PMID   11517304.
  103. Wolf FI, Fasanella S, Tedesco B, Cavallini G, Donati A, Bergamini E, Cittadini A (March 2005). "Peripheral lymphocyte 8-OHdG levels correlate with age-associated increase of tissue oxidative DNA damage in Sprague-Dawley rats. Protective effects of caloric restriction". Experimental Gerontology. 40 (3): 181–8. doi:10.1016/j.exger.2004.11.002. PMID   15763395. S2CID   23752647.
  104. Anson RM, Bohr VA (October 2000). "Mitochondria, oxidative DNA damage, and aging". Journal of the American Aging Association. 23 (4): 199–218. doi:10.1007/s11357-000-0020-y. PMC   3455271 . PMID   23604866.
  105. Vijg J (July 2021). "From DNA damage to mutations: All roads lead to aging". Ageing Research Reviews. 68: 101316. doi:10.1016/j.arr.2021.101316. PMC   10018438 . PMID   33711511.
  106. Rees K, Takeda A, Martin N, Ellis L, Wijesekara D, Vepa A, et al. (Cochrane Heart Group) (March 2019). "Mediterranean-style diet for the primary and secondary prevention of cardiovascular disease". The Cochrane Database of Systematic Reviews. 2019 (3): CD009825. doi:10.1002/14651858.CD009825.pub3. PMC   6414510 . PMID   30864165.
  107. Sofi F, Cesari F, Abbate R, Gensini GF, Casini A (September 2008). "Adherence to Mediterranean diet and health status: meta-analysis". BMJ. 337 (sep11 2): a1344. doi:10.1136/bmj.a1344. PMC   2533524 . PMID   18786971.
  108. de Gaetano G (29 August 2016). "Mediterranean diet associated with lower risk of early death in cardiovascular disease patients. European Society of Cardiology". ScienceDaily.
  109. Lee MB, Hill CM, Bitto A, Kaeberlein M (November 2021). "Antiaging diets: Separating fact from fiction". Science. 374 (6570): eabe7365. doi:10.1126/science.abe7365. PMC   8841109 . PMID   34793210.
  110. United States Department of Health And Human Services (1996). Physical activity and health: a report of the Surgeon General. United States Department of Health and Human Services. ISBN   978-1-4289-2794-0.
  111. 1 2 Kyu HH, Bachman VF, Alexander LT, Mumford JE, Afshin A, Estep K, et al. (August 2016). "Physical activity and risk of breast cancer, colon cancer, diabetes, ischemic heart disease, and ischemic stroke events: systematic review and dose-response meta-analysis for the Global Burden of Disease Study 2013". BMJ. 354: i3857. doi:10.1136/bmj.i3857. PMC   4979358 . PMID   27510511.
  112. 1 2 3 4 5 Zhao, Haotian; Cheng, Ruihong; Song, Ge; Teng, Jin; Shen, Siqin; Fu, Xuancheng; Yan, Yi; Liu, Chang (January 2022). "The Effect of Resistance Training on the Rehabilitation of Elderly Patients with Sarcopenia: A Meta-Analysis". International Journal of Environmental Research and Public Health. 19 (23): 15491. doi: 10.3390/ijerph192315491 . ISSN   1660-4601.
  113. 1 2 3 4 Rodrigues, Filipe; Domingos, Christophe; Monteiro, Diogo; Morouço, Pedro (January 2022). "A Review on Aging, Sarcopenia, Falls, and Resistance Training in Community-Dwelling Older Adults". International Journal of Environmental Research and Public Health. 19 (2): 874. doi: 10.3390/ijerph19020874 . ISSN   1660-4601. PMC   8775372 . PMID   35055695.
  114. 1 2 3 Wang, Qianjin; Cui, Can; Zhang, Ning; Lin, Wujian; Chai, Senlin; Chow, Simon Kwoon-Ho; Wong, Ronald Man Yeung; Hu, Yong; Law, Sheung Wai; Cheung, Wing-Hoi (1 May 2024). "Effects of physical exercise on neuromuscular junction degeneration during ageing: A systematic review". Journal of Orthopaedic Translation. 46: 91–102. doi:10.1016/j.jot.2024.03.007. ISSN   2214-031X. PMC   11137388 . PMID   38817243.
  115. Holt-Lunstad J, Smith TB, Layton JB (July 2010). "Social relationships and mortality risk: a meta-analytic review". PLOS Medicine. 7 (7): e1000316. doi: 10.1371/journal.pmed.1000316 . PMC   2910600 . PMID   20668659.
  116. Phillips, Judith, Kristine Ajrouch, and Sarah Hillcoat-Nallétamby (2010) Key Concepts in Social Gerontology. SAGE Publications. ISBN   978-1-4462-0428-3. pp. 12–13.
  117. Levy BR, Slade MD, Chang ES, Kannoth S, Wang SY (January 2020). "Ageism Amplifies Cost and Prevalence of Health Conditions". The Gerontologist. 60 (1): 174–181. doi: 10.1093/geront/gny131 . PMC   7182003 . PMID   30423119.
  118. 1 2 3 4 5 6 7 "Ageing in the Twenty-First Century". UNFPA. 2012.
  119. LO W (2015). "The music culture of older adults in Cantonese operatic singing lessons". Ageing and Society. 35 (8): 1614–34. doi:10.1017/S0144686X14000439. S2CID   144367063.
  120. Vincent JA (December 2005). "Understanding generations: political economy and culture in an ageing society". The British Journal of Sociology. 56 (4): 579–99. doi:10.1111/j.1468-4446.2005.00084.x. PMID   16309437. S2CID   1775770.
  121. "Population Ageing and Development". UNFPA. 2002.
  122. 1 2 "Ageing". unfpa.org. UNFPA – United Nations Population Fund.
  123. "UN Human Development Report 2005" (PDF). United Nations Development Programme. Archived from the original (PDF) on 27 May 2008. Retrieved 7 October 2010.
  124. 1 2 Chosewood LC (19 July 2012). "Safer and Healthier at Any Age: Strategies for an Aging Workforce". NIOSH Science Blog. National Institute for Occupational Safety and Health. Retrieved 6 August 2012.
  125. Basakha M, Yavari K, Sadeghi H, Naseri A (2015). "Population Aging And Iran's Non-Oil Economic Growth". Payavard Salamat. 9 (2): 131–46.
  126. Basakha M, Yavari K, Sadeghi H, Naseri A (2014). "Health care cost disease as a threat to Iranian aging society". Journal of Research in Health Sciences. 14 (2): 152–6. PMID   24728752.
  127. Scheid TL, Brown TN (2010). A Handbook for the Study of Mental Health (Second ed.). New York: Cambridge University Press.
  128. Panek PE, Hayslip B (1989). Adult development and aging. San Francisco: Harper & Row. ISBN   978-0-06-045012-0.[ page needed ]
  129. Barfield, Woodrow (2015). Cyber-humans : our future with machines. Cham. ISBN   978-3-319-25048-9.{{cite book}}: CS1 maint: location missing publisher (link)
  130. Wejbrandt A (December 2014). "Defining aging in cyborgs: a bio-techno-social definition of aging". Journal of Aging Studies. 31: 104–9. doi:10.1016/j.jaging.2014.09.003. PMID   25456627.
  131. Emmanuel EJ (October 2014). "Why I hope to die at 75: An argument that society and families – and you – will be better off if nature takes its course swiftly and promptly". The Atlantic. Retrieved 7 April 2015.
  132. Faria MA (2015). "Bioethics and why I hope to live beyond age 75 attaining wisdom!: A rebuttal to Dr. Ezekiel Emanuel's 75 age limit". Surgical Neurology International. 6: 35. doi: 10.4103/2152-7806.152733 . PMC   4360549 . PMID   25789197.
  133. Faria MA (2015). "Longevity and compression of morbidity from a neuroscience perspective: Do we have a duty to die by a certain age?". Surgical Neurology International. 6: 49. doi: 10.4103/2152-7806.154273 . PMC   4392568 . PMID   25883841.
  134. Saltman RB, Dubois HF, Chawla M (2006). "The impact of aging on long-term care in Europe and some potential policy responses". International Journal of Health Services. 36 (4): 719–46. doi:10.2190/AUL1-4LAM-4VNB-3YH0. PMID   17175843. S2CID   45396303.
  135. Reinhardt UE (2003). "Does the aging of the population really drive the demand for health care?". Health Affairs. 22 (6): 27–39. doi: 10.1377/hlthaff.22.6.27 . PMID   14649430.
  136. Meara E, White C, Cutler DM (2004). "Trends in medical spending by age, 1963–2000". Health Affairs. 23 (4): 176–83. doi: 10.1377/hlthaff.23.4.176 . PMID   15318578.
  137. Kattimani V, Tiwari RV, Gufran K, Wasan B, Shilpa PH, Khader AA (March 2019). "Botulinum Toxin Application in Facial Esthetics and Recent Treatment Indications (2013–2018)". Journal of International Society of Preventive & Community Dentistry. 9 (2): 99–105. doi: 10.4103/jispcd.JISPCD_430_18 . PMC   6489509 . PMID   31058058. Standards of beauty have changed through centuries with increased awareness about esthetics.
  138. Juhász ML, Levin MK, Marmur ES (June 2018). "The use of natural ingredients in innovative Korean cosmeceuticals". Journal of Cosmetic Dermatology. 17 (3): 305–312. doi:10.1111/jocd.12492. PMID   29363245. S2CID   25982162.[ verification needed ]
  139. "Botox injections – Mayo Clinic". www.mayoclinic.org. Retrieved 12 March 2021.
  140. "Korea – Birthday Celebrations". www.asianinfo.org. Retrieved 12 March 2021.
  141. Sabatini S, Silarova B, Martyr A, Collins R, Ballard C, Anstey KJ, et al. (August 2020). "Associations of Awareness of Age-Related Change With Emotional and Physical Well-being: A Systematic Review and Meta-analysis". The Gerontologist. 60 (6): e477–e490. doi: 10.1093/geront/gnz101 . PMC   7427487 . PMID   31350849.
  142. Idler EL (2003). "Discussion: Gender Differences in Self-Rated Health, in Mortality, and in the Relationship Between the Two". The Gerontologist. 43 (3): 372–75. doi: 10.1093/geront/43.3.372 .
  143. 1 2 Deeg DJ, Bath PA (June 2003). "Self-rated health, gender, and mortality in older persons: introduction to a special section". The Gerontologist. 43 (3): 369–71. doi: 10.1093/geront/43.3.369 . PMID   12810900.
  144. 1 2 Benyamini Y, Blumstein T, Lusky A, Modan B (June 2003). "Gender differences in the self-rated health-mortality association: is it poor self-rated health that predicts mortality or excellent self-rated health that predicts survival?". The Gerontologist. 43 (3): 396–405, discussion 372–5. doi: 10.1093/geront/43.3.396 . PMID   12810904.
  145. Kunzmann U, Little TD, Smith J (September 2000). "Is age-related stability of subjective well-being a paradox? Cross-sectional and longitudinal evidence from the Berlin Aging Study". Psychology and Aging. 15 (3): 511–26. doi:10.1037/0882-7974.15.3.511. PMID   11014714.
  146. Jylhä M, Guralnik JM, Balfour J, Fried LP (October 2001). "Walking difficulty, walking speed, and age as predictors of self-rated health: the women's health and aging study". The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences. 56 (10): M609-17. doi: 10.1093/gerona/56.10.m609 . PMID   11584033.
  147. Heckhausen J (1999). Developmental Regulation in Adulthood: Age-Normative and Sociostructural Constraints as Adaptive Challenges . Cambridge University Press. ISBN   978-0-521-02713-7.
  148. Sargent-Cox KA, Anstey KJ, Luszcz MA (September 2008). "Determinants of self-rated health items with different points of reference: implications for health measurement of older adults". Journal of Aging and Health. 20 (6): 739–61. doi:10.1177/0898264308321035. PMID   18625760. S2CID   34866893.
  149. Idler EL (November 1993). "Age differences in self-assessments of health: age changes, cohort differences, or survivorship?". Journal of Gerontology. 48 (6): S289-300. doi:10.1093/geronj/48.6.s289. PMID   8228003.
  150. Williamson JD, Fried LP (December 1996). "Characterization of older adults who attribute functional decrements to "old age"". Journal of the American Geriatrics Society . 44 (12): 1429–34. doi:10.1111/j.1532-5415.1996.tb04066.x. PMID   8951311. S2CID   21027678.
  151. 1 2 "40 Years In 5 Minutes: Age Simulation Suit Aims To Increase Empathy In Building Design". www.wbur.org. 3 June 2019. Retrieved 12 March 2021.
  152. Prindle D (7 January 2016). "Hands on: Genworth R70i Exoskeleton". digitaltrends. Archived from the original on 8 January 2016. Retrieved 12 March 2021.
  153. 1 2 "AGNES (Age Gain Now Empathy System) | MIT AgeLab". agelab.mit.edu. Archived from the original on 6 April 2021. Retrieved 12 March 2021.
  154. World Health Organization (2015). World report on ageing and health. World Health Organization. hdl:10665/186463. ISBN   978-92-4-156504-2.
  155. World Health Organization (2015). World report on ageing and health. World Health Organization. hdl:10665/186463. ISBN   978-92-4-156504-2.
  156. González-Bautista, Emmanuel; de Souto Barreto, Philipe; Andrieu, Sandrine; et al. (August 2021). "Screening for intrinsic capacity impairments as markers of increased risk of frailty and disability in the context of integrated care for older people: Secondary analysis of MAPT". Maturitas. 150: 1–6. doi:10.1016/j.maturitas.2021.05.011. ISSN   1873-4111. PMID   34274071.
  157. Gonzalez-Bautista, Emmanuel; Llibre-Guerra, Jorge Jesus; Sosa, Ana L; et al. (1 July 2023). "Exploring the natural history of intrinsic capacity impairments: longitudinal patterns in the 10/66 study". Age and Ageing. 52 (7). doi:10.1093/ageing/afad137. ISSN   0002-0729. PMC   10387229 . PMID   37517058.
  158. Baltes PB, Baltes MM (1990). "Psychological perspectives on successful aging: The model of selective optimization with compensation". In Baltes PB, Baltes MM (eds.). Successful Aging. pp. 1–34. doi:10.1017/CBO9780511665684.003. ISBN   978-0-511-66568-4.
  159. Rowe JW, Kahn RL (July 1987). "Human aging: usual and successful". Science. 237 (4811): 143–9. Bibcode:1987Sci...237..143R. doi:10.1126/science.3299702. PMID   3299702.
  160. Jensen A, Claunch K, Verdeja M, Dungan M, Goates M, Thacker E (11 November 2018). "Successful Aging: Cross-Cultural Comparison of Older Adults' Lay Perspectives". Innovation in Aging. 2 (Suppl 1): 167. doi:10.1093/geroni/igy023.601. ISSN   2399-5300. PMC   6229246 .
  161. Job 14:5–7: New Life Version