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Thursday, August 29, 2024

Ageing

From Wikipedia, the free encyclopedia
https://en.wikipedia.org/wiki/Ageing

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. In a broader sense, ageing can refer to single cells within an organism which have ceased dividing, or to the population of a species.

In humans, ageing 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 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. Of the roughly 150,000 people who die each day across the globe, about two-thirds die from age-related causes. Certain lifestyle choices and socioeconomic conditions have been linked to ageing.

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) 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

Human beings and members of other species, especially animals, age and die. Fungi, too, can age. 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, were single-celled organisms. Such organisms (Prokaryotes, Protozoans, algae) multiply by fission into daughter cells, thus do not age and are potentially immortal under favourable conditions.

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

Symptoms

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)
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.

  • Teenagers lose the young child's ability to hear high-frequency sounds above 20 kHz.
  • Wrinkles develop mainly due to photoageing, particularly affecting sun-exposed areas such as the face.
  • After peaking from the late teens to the late 20s, female fertility declines.
  • After age 30, the mass of the human body is decreased until 70 years and then shows damping oscillations.
  • People over 35 years of age are at increasing risk for losing strength in the ciliary muscle of the eyes, which leads to difficulty focusing on close objects, or presbyopia. Most people experience presbyopia by age 45–50. The cause is lens hardening by decreasing levels of alpha-crystallin, a process which may be sped up by higher temperatures.
  • Around age 55, hair turns grey. Pattern hair loss by the age of 55 affects about 30–50% of males and a quarter of females.
  • Menopause typically occurs between 44 and 58 years of age.
  • In the 60–64 age cohort, the incidence of osteoarthritis rises to 53%. Only 20%, however, report disabling osteoarthritis at this age.
  • Almost half of people older than 75 have hearing loss (presbycusis), inhibiting spoken communication. Many vertebrates such as fish, birds and amphibians do not develop presbycusis in old age, as they are able to regenerate their cochlear sensory cells; mammals, including humans, have genetically lost this ability.
  • By age 80, more than half of all Americans either have a cataract or have had cataract surgery.
  • Frailty, a syndrome of decreased strength, physical activity, physical performance and energy, affects 25% of those over 85. Muscles have a reduced capacity of responding to exercise or injury and loss of muscle mass and strength (sarcopenia) is common. Maximum oxygen use and maximum heart rate decline. Hand strength and mobility decrease.
  • Atherosclerosis is classified as an ageing disease. It leads to cardiovascular disease (for example, stroke and heart attacks), which, globally, is the most common cause of death. Vessel ageing causes vascular remodelling and loss of arterial elasticity, and as a result, causes the stiffness of the vasculature.
  • Evidence suggests that age-related risk of death plateaus after the age of 105. The maximum human lifespan is suggested to be 115 years. The oldest reliably recorded human was Jeanne Calment, who died in 1997 at 122.

Dementia becomes more common with age. 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. 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 (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. 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 experience 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 the growth of abnormal vessels around the retina.

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. 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. 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.

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).

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. In industrialized nations, the proportion is higher, reaching 90%.

Biological basis

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. 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. Most known mutations and RNA interference targets that extend lifespan were first discovered in C. elegans.

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

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:

  • genomic instability (mutations accumulated in nuclear DNA, in mtDNA, and in the nuclear lamina)
  • telomere attrition (the authors note that artificial telomerase confers non-cancerous immortality to otherwise mortal cells)
  • epigenetic alterations (including DNA methylation patterns, post-translational modification of histones, and chromatin remodelling). Ageing and disease are related to a misregulation of gene expression through impaired methylation patterns, from hypomethylation to hypermethylation. 
  • loss of proteostasis (protein folding and proteolysis)
  • deregulated nutrient sensing (relating to the Growth hormone/Insulin-like growth factor 1 signalling pathway, which is the most conserved ageing-controlling pathway in evolution and among its targets are the FOXO3/Sirtuin transcription factors and the mTOR complexes, probably responsive to caloric restriction)
  • mitochondrial dysfunction (the authors point out however that a causal link between ageing and increased mitochondrial production of reactive oxygen species is no longer supported by recent research)
  • cellular senescence (accumulation of no longer dividing cells in certain tissues, a process induced especially by p16INK4a/Rb and p19ARF/p53 to stop cancerous cells from proliferating)
  • stem cell exhaustion (in the authors' view caused by damage factors such as those listed above)
  • altered intercellular communication (encompassing especially inflammation but possibly also other intercellular interactions
  • inflammageing, a chronic inflammatory phenotype in the elderly in the absence of viral infection, due to over-activation and a decrease in the precision of the innate immune system
  • dysbiosis of gut microbiome (e.g., loss of microbial diversity, expansion of enteropathogens, and altered vitamin B12 biosynthesis) is correlated with biological age rather than chronological age.

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.

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. 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 (known as quahog in New England) 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.

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

Main article: DNA damage theory of aging

  • DNA damage theory of ageing: DNA damage is thought to be the common basis of both cancer and ageing, and it has been argued that intrinsic causes of DNA damage are the most important causes of ageing. Genetic damage (aberrant structural alterations of the DNA), mutations (changes in the DNA sequence), and epimutations (methylation of gene promoter regions or alterations of the DNA scaffolding which regulate gene expression), can cause abnormal gene expression. DNA damage causes the cells to stop dividing or induces apoptosis, often affecting stem cell pools and therefore hindering regeneration. However, lifelong studies of mice suggest that most mutations happen during embryonic and childhood development, when cells divide often, as each cell division is a chance for errors in DNA replication.
  • Genetic instability: Dogs annually lose approximately 3.3% of the DNA in their heart muscle cells while humans lose approximately 0.6% of their heart muscle DNA each year. These numbers are close to the ratio of the maximum longevities of the two species (120 years vs. 20 years, a 6/1 ratio). The comparative percentage is also similar between the dog and human for yearly DNA loss in the brain and lymphocytes. As stated by lead author, Bernard L. Strehler, "... genetic damage (particularly gene loss) is almost certainly (or probably the) central cause of ageing."
  • Accumulation of waste:
    • A buildup of waste products in cells presumably interferes with metabolism. For example, a waste product called lipofuscin is formed by a complex reaction in cells that binds fat to proteins. Lipofuscin may accumulate in the cells as small granules during ageing.
    • The hallmark of ageing yeast cells appears to be overproduction of certain proteins.
    • Autophagy induction can enhance clearance of toxic intracellular waste associated with neurodegenerative diseases and has been comprehensively demonstrated to improve lifespan in yeast, worms, flies, rodents and primates. The situation, however, has been complicated by the identification that autophagy up-regulation can also occur during ageing.
  • Wear-and-tear theory: The general idea that changes associated with ageing are the result of chance damage that accumulates over time.
  • Accumulation of errors: The idea that ageing results from chance events that escape proofreading mechanisms, which gradually damages the genetic code.
  • Heterochromatin loss, model of ageing.
  • Cross-linkage: The idea that ageing results from accumulation of cross-linked compounds that interfere with normal cell function.
  • Studies of mtDNA mutator mice have shown that increased levels of somatic mtDNA mutations directly can cause a variety of ageing phenotypes. The authors propose that mtDNA mutations lead to respiratory-chain-deficient cells and thence to apoptosis and cell loss. They cast doubt experimentally however on the common assumption that mitochondrial mutations and dysfunction lead to increased generation of reactive oxygen species (ROS).
  • Free-radical theory: Damage by free radicals, or more generally reactive oxygen species or oxidative stress, create damage that may give rise to the symptoms we recognise as ageing. The effect of calorie restriction may be due to increased formation of free radicals within the mitochondria, causing a secondary induction of increased antioxidant defence capacity.
  • Mitochondrial theory of ageing: free radicals produced by mitochondrial activity damage cellular components, leading to ageing.
  • DNA oxidation and caloric restriction: Caloric restriction reduces 8-OH-dG DNA damage in organs of ageing rats and mice. Thus, reduction of oxidative DNA damage is associated with a slower rate of ageing and increased lifespan. In a 2021 review article, Vijg stated that "Based on an abundance of evidence, DNA damage is now considered as the single most important driver of the degenerative processes that collectively cause ageing."

Research

Diet

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, such as by consuming olive oil.

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

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. The majority of the benefits from exercise are achieved with around 3500 metabolic equivalent (MET) 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.

Social factors

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

Society and culture

A grandmother and her grandchild

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 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).

Ageism cost the United States $63 billion in one year according to a Yale School of Public Health study. 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". 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 ageing. 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."

Economics

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.

In the 21st century, one of the most significant population trends is ageing. 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%. 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".

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 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."

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".

It has been argued that population ageing has undermined economic development 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."

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.

Sociology

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. 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. As cyborgs currently are on the rise some theorists argue there is a need to develop new definitions of ageing and for instance a bio-techno-social definition of ageing has been suggested.

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 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.

However, the annual growth in national health spending is not mainly due to increasing demand from ageing populations, but rather has been driven by rising incomes, costly new medical technology, a shortage of health care workers and informational asymmetries between providers and patients. A number of health problems become more prevalent as people get older. These include mental health problems as well as physical health problems, especially dementia.

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.

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.

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). Another substance used to prevent the physical manifestations of ageing is onobotulinumtoxinA, the toxin injected for Botox.

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. 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. Positive self-perception of health has been correlated with higher well-being and reduced mortality among the elderly. 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. 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 ageing". 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 ageing process.

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. 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. 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 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. Intrinsic capacity comprises the domains of: cognition, locomotion, vitality/nutrition, psychological and sensory (visual and hearing). 

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.

Successful ageing

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

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.

Neuroscience of aging

From Wikipedia, the free encyclopedia
 

The neuroscience of aging is the study of the changes in the nervous system that occur with ageing. Aging is associated with many changes in the central nervous system, such as mild atrophy of the cortex that is considered non-pathological. Aging is also associated with many neurological and neurodegenerative disease such as amyotrophic lateral sclerosis, dementia, mild cognitive impairment, Parkinson's disease, and Creutzfeldt–Jakob disease.

Normal structural and neural changes

Neurogenesis occurs very little in adults, only occurring in the hypothalamus and striatum to a small extent in a process called adult neurogenesis. The volume of the brain actually decrease roughly 5% per decade after forty. It is currently unclear why brain volume decreases with age, however, a few causes may include: cell death, decreased cell volume, and changes in synaptic structure. The changes in brain volume is heterogenous across regions with prefrontal cortex receiving the most significant reduction in volume followed in order by the striatum, the temporal lobe, cerebellar vermis, cerebellar hemispheres, and the hippocampus. However, one review found that the amygdala and ventromedial prefrontal cortex remained relatively free of atrophy, which is consistent with the finding of emotional stability occurring with non-pathological aging. Enlargement of the ventricles, sulci and fissures are also common in non-pathological aging.

Changes may also be associated with neuroplasticity, synaptic functionality and voltage gated calcium channels. Increased magnitude of hyperpolarization, possibly a result of dysfunctional calcium regulation, leads to decreased firing rate of neurons and decreased plasticity. This effect is particularly pronounced in the hippocampus of aged animals, and may be an important contributor to age-associated memory deficits. The hyperpolarization of a neuron can be divided into three stages: the fast, medium and slow hyperpolarization. In aged neurons, the medium and slow hyperpolarization phases involve the prolonged opening of calcium-dependent potassium channels. The prolonging of this phase has been hypothesized to be a result of deregulated calcium and hypoactivity of cholinergic, dopaminergic, serotonergic and glutaminergic pathways.

Normal functional changes

Episodic memory starts to decline gradually from middle age, while semantic memory increases all the way into early old age and declines thereafter. Older adults tend to engage their prefrontal cortex more often during working memory tasks, possibly to compensate with executive functions. Further impairments of cognitive function associated with aging include decrease in processing speed and inability to focus. A model proposed to account for altered activation posits that decreased neural efficiency driven by amyloid plaques and decreased dopamine functionality lead to compensatory activation. Decreased processing of negative stimuli as opposed to positive stimuli appear in aging, become significant enough to detect even with autonomic nervous responses to emotionally charged stimuli. Aging is also associated with decreased plantar reflex and achilles reflex response. Nerve conductance also decreases during normal aging.

DNA damage

Certain genes of the human frontal cortex display reduced transcriptional expression after age 40, and especially after age 70. In particular, genes that have central roles in synaptic plasticity display reduced expression with age. The promoters of genes with reduced expression in the cortex of older individuals have a marked increase in DNA damage, likely oxidative DNA damage.

Pathological changes

Roughly 20% of persons greater than 60 years of age have a neurological disorder, with episodic disorders being the most common followed by extrapyramidal movement disorders, and nerve disorders. Diseases commonly associated with old age include

The misfolding of proteins is a common component of the proposed pathophysiology of many diseases associated with aging, however there is insufficient evidence to prove this. For example, the tau hypothesis to Alzheimer's proposes that tau protein accumulation results in the breakdown neuron cytoskeletons leading to Alzheimer's. Another proposed mechanism for Alzheimer's is related to the accumulation of amyloid beta,. in a similar mechanism to the prion propagation of Creutzfeldt-Jakob disease. Similarly the protein alpha-synuclein is hypothesized to accumulate in Parkinson's and related diseases.

Chemo brain

Treatments with anticancer chemotherapeutic agents often are toxic to the cells of the brain, leading to memory loss and cognitive dysfunction that can persist long after the period of exposure. This condition, termed chemo brain, appears to be due to DNA damages that cause epigenetic changes in the brain that accelerate the brain aging process.

Management

Treatment of an age related neurological disease varies from disease to disease. Modifiable risk factors for dementia include diabetes, hypertension, smoking, hyperhomocysteinemia, hypercholesterolemia, and obesity (which is usually associated with many other risk factors for dementia). Paradoxically, smoking confers protection against Parkinson's disease. Also conferring protective benefits to age related neurological disease in consumption of coffee or caffeine. Consumption of fruits, fish and vegetables confer protection against dementia, as does a Mediterranean diet. Physical exercise significantly lowers the risk of cognitive decline in old age, and is an effective treatment for those with dementia and Parkinson's disease.

Aging brain

From Wikipedia, the free encyclopedia
https://en.wikipedia.org/wiki/Aging_brain

Aging of the brain is a process of transformation of the brain in older age, including changes all individuals experience and those of illness (including unrecognised illness). Usually this refers to humans.

Since life extension is only pertinent if accompanied by health span extension, and, more importantly, by preserving brain health and cognition, finding rejuvenating approaches that act simultaneously in peripheral tissues and in brain function is a key strategy for development of rejuvenating technology.

Aging is a major risk factor for most common neurodegenerative diseases, including mild cognitive impairment, dementias including Alzheimer's disease, cerebrovascular disease, Parkinson's disease, and Lou Gehrig's disease. While much research has focused on diseases of aging, there are few informative studies on the molecular biology of the aging brain (usually spelled ageing brain in British English) in the absence of neurodegenerative disease or the neuropsychological profile of healthy older adults. However, research suggests that the aging process is associated with several structural, chemical, and functional changes in the brain as well as a host of neurocognitive changes. Recent reports in model organisms suggest that as organisms age, there are distinct changes in the expression of genes at the single neuron level. This page is an overview of the changes associated with human brain aging, including aging without concomitant diseases.

Structural changes

Human brain in the sagittal plane
Ventricles of the brain

Aging entails many physical, biological, chemical, and psychological changes and the brain is no exception to this phenomenon. These various changes have attempted to be mapped by conceptual models like the Scaffolding Theory of Aging and Cognition (STAC) in 2009. The STAC model looks at factors like neural changes to the white matter, dopamine depletion, shrinkage, and cortical thinning. CT scans have found that the cerebral ventricles expand as a function of age. More recent MRI studies have reported age-related regional decreases in cerebral volume. Regional volume reduction is not uniform; some brain regions shrink at a rate of up to 1% per year, whereas others remain relatively stable until the end of the life-span. The brain is very complex, and is composed of many different areas and types of tissue, or matter. The different functions of different tissues in the brain may be more or less susceptible to age-induced changes. The brain matter can be broadly classified as either grey matter, or white matter. Grey matter consists of cell bodies in the cortex and subcortical nuclei. White matter consists of tightly packed myelinated axons connecting the neurons to each other and with the periphery.

Loss of neural circuits and brain plasticity

Brain plasticity refers to the brain's ability to change structure and function. This ties into the common phrase, "if you don't use it, you lose it," which is another way of saying, if you do not use it, your brain will devote less somatotopic space for it. One proposed mechanism for the observed age-related plasticity deficits in animals is the result of age-induced alterations in calcium regulation. The changes in the organism's abilities to handle calcium will ultimately influence neuronal firing and the ability to propagate action potentials, which in turn would affect the ability of the brain to alter its structure or function (i.e. its plastic nature). Due to the complexity of the brain, with all of its structures and functions, it is logical to assume that some areas would be more vulnerable to aging than others. Two circuits worth mentioning here are the hippocampal and neocortical circuits. It has been suggested that age-related cognitive decline is due in part not to neuronal death but to synaptic alterations. Evidence in support of this idea from animal work has also suggested that this cognitive deficit is due to functional and biochemical factors such as changes in enzymatic activity, chemical messengers, or gene expression in cortical circuits.

Thinning of the cortex

Lobes of the human brain

Advances in MRI technology have provided the ability to see the brain structure in great detail in an easy, non-invasive manner in vivo. Bartzokis et al., has noted that there is a decrease in grey matter volume between adulthood and old age, whereas white matter volume was found to increase from age 19–40, and decline after this age. Studies using Voxel-based morphometry have identified areas such as the insula and superior parietal gyri as being especially vulnerable to age-related losses in grey matter of older adults. Sowell et al., reported that the first 6 decades of an individual's life were correlated with the most rapid decreases in grey matter density, and this occurred over dorsal, frontal, and parietal lobes on both interhemispheric and lateral brain surfaces. It is also worth noting that areas such as the cingulate gyrus, and occipital cortex surrounding the calcarine sulcus appear exempt from this decrease in grey matter density over time. Age effects on grey matter density in the posterior temporal cortex appear more predominantly in the left versus right hemisphere, and were confined to posterior language cortices. Certain language functions such as word retrieval and production were found to be located to more anterior language cortices, and deteriorate as a function of age. Sowell et al., also reported that these anterior language cortices were found to mature and decline earlier than the more posterior language cortices. It has also been found that the width of sulcus not only increases with age, but also with cognitive decline in the elderly.

Morphology and microstructure

Age-related decrease in gray matter volume was the largest contribution to changes in brain volume. Moreover, neuronal density appears to decrease, white matter microstructure gets altered and energy metabolism in the cerebellum gets altered. General cortical atrophy occurs in aging and e.g. the caudate nucleus volume appears to decrease.

There is converging evidence from cognitive neuroscientists around the world that age-induced cognitive deficits may not be due to neuronal loss or cell death, but rather may be the result of small region-specific changes to the morphology of neurons. Studies by Duan et al., have shown that dendritic arbors and dendritic spines of cortical pyramidal neurons decrease in size and/or number in specific regions and layers of human and non-human primate cortex as a result of age (Duan et al., 2003; morph). A 46% decrease in spine number and spine density has been reported in humans older than 50 compared with younger individuals. An electron microscopy study in monkeys reported a 50% loss in spines on the apical dendritic tufts of pyramidal cells in prefrontal cortex of old animals (27–32 years old) compared with young ones (6–9 years old).

Neurofibrillary tangles

Tau protein disorders cause microtubule destruction and formation of neurofibrillary tangles.

Age-related neuropathologies such as Alzheimer's disease, Parkinson's disease, diabetes, hypertension and arteriosclerosis make it difficult to distinguish the normal patterns of aging. One of the important differences between normal aging and pathological aging is the location of neurofibrillary tangles. Neurofibrillary tangles are composed of paired helical filaments (PHF). In normal, non-demented aging, the number of tangles in each affected cell body is relatively low and restricted to the olfactory nucleus, parahippocampal gyrus, amygdala and entorhinal cortex. As the non-demented individual ages, there is a general increase in the density of tangles, but no significant difference in where tangles are found.

The other main neurodegenerative contributor commonly found in the brain of patients with AD is amyloid plaques. However, unlike tangles, plaques have not been found to be a consistent feature of normal aging.

Role of oxidative stress

Cognitive impairment has been attributed to oxidative stress, inflammatory reactions and changes in the cerebral microvasculature. The exact impact of each of these mechanisms in affecting cognitive aging is unknown. Oxidative stress is the most controllable risk factor and is the best understood. The online Merriam-Webster Medical Dictionary defines oxidative stress as, "physiological stress on the body that is caused by the cumulative damage done by free radicals inadequately neutralized by antioxidants and that is held to be associated with aging." Hence oxidative stress is the damage done to the cells by free radicals that have been released from the oxidation process.

Compared to other tissues in the body, the brain is deemed unusually sensitive to oxidative damage. Increased oxidative damage has been associated with neurodegenerative diseases, mild cognitive impairment and individual differences in cognition in healthy elderly people. In 'normal aging', the brain is undergoing oxidative stress in a multitude of ways. The main contributors include protein oxidation, lipid peroxidation and oxidative modifications in nuclear and mitochondrial DNA. Oxidative stress can damage DNA replication and inhibit repair through many complex processes, including telomere shortening in DNA components. Each time a somatic cell replicates, the telomeric DNA component shortens. As telomere length is partly inheritable, there are individual differences in the age of onset of cognitive decline.

DNA damage

At least 25 studies have demonstrated that DNA damage accumulates with age in the mammalian brain. This DNA damage includes the oxidized nucleoside 8-hydroxydeoxyguanosine (8-OHdG), single- and double-strand breaks, DNA-protein cross-links and malondialdehyde adducts (reviewed in Bernstein et al.). Increasing DNA damage with age has been reported in the brains of the mouse, rat, gerbil, rabbit, dog, and human. Young 4-day-old rats have about 3,000 single-strand breaks and 156 double-strand breaks per neuron, whereas in rats older than 2 years the level of damage increases to about 7,400 single-strand breaks and 600 double-strand breaks per neuron.

Lu et al. studied the transcriptional profiles of the human frontal cortex of individuals ranging from 26 to 106 years of age. This led to the identification of a set of genes whose expression was altered after age 40. They further found that the promoter sequences of these particular genes accumulated oxidative DNA damage, including 8-OHdG, with age (see DNA damage theory of aging). They concluded that DNA damage may reduce the expression of selectively vulnerable genes involved in learning, memory and neuronal survival, initiating a pattern of brain aging that starts early in life.

Immune system and fluids

Blood–brain barrier permeability, neuroinflammation and neurodegeneration, and gut microbiota-induced systemic chronic inflammation appear to be linked and interact with aging, e.g. as gut microbiota homeostasis could be disturbed by increasing age. According to a review, neuroinflammatory changes, "including microglial activation and production of inflammatory cytokines", occur with normal aging.

Fluids

Cerebral blood flow was shown to decrease 0.3-0.5% per year in healthy ageing. An efficiently functioning glymphatic system, involved in waste clearance, may be important for maintaining brain health and its transport efficiency appears to be declining with aging. Factors in the circulation have been shown to modulate ageing and to rejuvenate the brain.

Chemical changes

A labelled line drawing of dopamine pathways superimposed on a drawing of the human brain.
Major dopamine pathways.

As part of the reward pathway, dopamine is manufactured in nerve cell bodies located within VTA and is released in the nucleus accumbens and the prefrontal cortex. The motor functions of dopamine are linked to a separate pathway, with cell bodies in the substantia nigra that manufacture and release dopamine into the striatum.
Dopamine and serotonin functions and pathways

In addition to the structural changes that the brain incurs with age, the aging process also entails a broad range of biochemical changes. More specifically, neurons communicate with each other via specialized chemical messengers called neurotransmitters. Several studies have identified a number of these neurotransmitters, as well as their receptors, that exhibit a marked alteration in different regions of the brain as part of the normal aging process.

Dopamine

An overwhelming number of studies have reported age-related changes in dopamine synthesis, binding sites, and number of receptors. Studies using positron emission tomography (PET) in living human subjects have shown a significant age-related decline in dopamine synthesis, notably in the striatum and extrastriatal regions (excluding the midbrain). Significant age-related decreases in dopamine receptors D1, D2, and D3 have also been highly reported. A general decrease in D1 and D2 receptors has been shown, and more specifically a decrease of D1 and D2 receptor binding in the caudate nucleus and putamen. A general decrease in D1 receptor density has also been shown to occur with age. Significant age-related declines in dopamine receptors, D2 and D3 were detected in the anterior cingulate cortex, frontal cortex, lateral temporal cortex, hippocampus, medial temporal cortex, amygdala, medial thalamus, and lateral thalamus. One study also indicated a significant inverse correlation between dopamine binding in the occipital cortex and age. Postmortem studies also show that the number of D1 and D2 receptors decline with age in both the caudate nucleus and the putamen, although the ratio of these receptors did not show age-related changes. The loss of dopamine with age is thought to be responsible for many neurological symptoms that increase in frequency with age, such as decreased arm swing and increased rigidity. Changes in dopamine levels may also cause age-related changes in cognitive flexibility.

Serotonin

Decreasing levels of different serotonin receptors and the serotonin transporter (5-HTT), have also been shown to occur with age. Studies conducted using PET methods on humans, in vivo, show that levels of the 5-HT2 receptor in the caudate nucleus, putamen, and frontal cerebral cortex, decline with age. A decreased binding capacity of the 5-HT2 receptor in the frontal cortex was also found, as well as a decreased binding capacity of the serotonin transporter (5-HHT) in the thalamus and the midbrain. Postmortem studies on humans have indicated decreased binding capacities of serotonin and a decrease in the number of S1 receptors in the frontal cortex and hippocampus as well as a decrease in affinity in the putamen.

Glutamate

Expression of glutamate transporter 1 in glial cell facilitates reuptake of glutamate and decreases extracellular glutamate concentration

Glutamate is another neurotransmitter that tends to decrease with age. Studies have shown older subjects to have lower glutamate concentration in the motor cortex compared to younger subjects. A significant age-related decline especially in the parietal gray matter, basal ganglia, and to a lesser degree, the frontal white matter, has also been noted. Although these levels were studied in the normal human brain, the parietal and basal ganglia regions are often affected in degenerative brain diseases associated with aging and it has therefore been suggested that brain glutamate may be useful as a marker of brain diseases that are affected by aging.

Neuropsychological changes

Changes in orientation

Orientation is defined as the awareness of self in relation to one's surroundings. Often orientation is examined by distinguishing whether a person has a sense of time, place, and person. Deficits in orientation are one of the most common symptoms of brain disease, hence tests of orientation are included in almost all medical and neuropsychological evaluations. While research has primarily focused on levels of orientation among clinical populations, a small number of studies have examined whether there is a normal decline in orientation among healthy aging adults. Results have been somewhat inconclusive. Some studies suggest that orientation does not decline over the lifespan. For example, in one study 92% of normal elderly adults (65–84 years) presented with perfect or near perfect orientation. However some data suggest that mild changes in orientation may be a normal part of aging. For example, Sweet and colleagues concluded that "older persons with normal, healthy memory may have mild orientation difficulties. In contrast, younger people with normal memory have virtually no orientation problems" (p. 505). So although current research suggests that normal aging is not usually associated with significant declines in orientation, mild difficulties may be a part of normal aging and not necessarily a sign of a particular pathology.

Changes in attention

Many older adults notice a decline in their attentional abilities. Attention is a broad construct that refers to "the cognitive ability that allows us to deal with the inherent processing limitations of the human brain by selecting information for further processing". Since the human brain has limited resources, people use their attention to zone in on specific stimuli and block out others.

If older adults have fewer attentional resources than younger adults, we would expect that when two tasks must be carried out at the same time, older adults' performance will decline more than that of younger adults. However, a large review of studies on cognition and aging suggest that this hypothesis has not been wholly supported. While some studies have found that older adults have a more difficult time encoding and retrieving information when their attention is divided, other studies have not found meaningful differences from younger adults. Similarly, one might expect older adults to do poorly on tasks of sustained attention, which measure the ability to attend to and respond to stimuli for an extended period of time. However, studies suggest that sustained attention shows no decline with age. Results suggest that sustained attention increases in early adulthood and then remains relatively stable, at least to the middle of the eighth decade of life. More research is needed on how normal aging impacts attention after age eighty.

It is worth noting that there are factors other than true attentional abilities that might relate to difficulty paying attention. For example, it is possible that sensory deficits impact older adults' attentional abilities. In other words, impaired hearing or vision may make it more difficult for older adults to do well on tasks of visual and verbal attention.

Changes in memory

Many different types of memory have been identified in humans, such as declarative memory (including episodic memory and semantic memory), working memory, spatial memory, and procedural memory. Studies done, have found that memory functions, more specifically those associated with the medial temporal lobe are especially vulnerable to age-related decline. A number of studies utilizing a variety of methods such as histological, structural imaging, functional imaging, and receptor binding have supplied converging evidence that the frontal lobes and frontal-striatal dopaminergic pathways are especially affected by age-related processes resulting in memory changes.

Changes in language

Changes in performance on verbal tasks, as well as the location, extent, and signal intensity of BOLD signal changes measured with functional MRI, vary in predictable patterns with age. For example, behavioral changes associated with age include compromised performance on tasks related to word retrieval, comprehension of sentences with high syntactic and/or working memory demands, and production of such sentences.

Brain activation patterns

The left inferior frontal junction and left anterior cuneus/precuneus were the only regions in a larger set of regions associated with executive functions, that consistently showed age differences in brain activity.

Changes in learning and behavioral flexibility

Learning is often more efficient in children and takes longer or is more difficult with age. A study using neuroimaging identified rapid neurotransmitter GABA boosting as a major potential explanation-component for why that is.

Behavioral flexibility can refer to efficiently and appropriately adapting to different situations and changing environmental demands, including the speed of adaptation, and to the capacity to develop solutions to novel problems or novel solutions to old problems. Studies indicate late-stage aging, and/or late-life dementias, decreases behavioral flexibility and impair deliberation about courses of action.

Genetic changes

Variation in the effects of aging among individuals can be attributed to both genetic, health, and environmental factors. As in so many other science disciplines, the nature versus nurture debate is an ongoing conflict in the field of cognitive neuroscience. The search for genetic factors has always been an important aspect in trying to understand neuropathological processes. Research focused on discovering the genetic component in developing Autosomal Dominant (AD) has also contributed greatly to the understanding the genetics behind normal or "non-pathological" aging.

Autosomal Dominant (AD) - Autosomal dominant is a pattern of inheritance characteristic of some genetic disorders. "Autosomal" means that the gene in question is located on one of the numbered, or non-sex, chromosomes. "Dominant" means that a single copy of the mutated gene (from one parent) is enough to cause the disorder.

The human brain shows a decline in function and a change in gene expression. This modulation in gene expression may be due to oxidative DNA damage at promoter regions in the genome. Genes that are down-regulated over the age of 40 include:

Genes that are upregulated include:

Measurement

Epigenetic age analysis of brain regions

The cerebellum is the youngest brain region (and probably body part) in centenarians according to an epigenetic biomarker of tissue age known as epigenetic clock: it is about 15 years younger than expected in a centenarian. By contrast, all brain regions and brain cells appear to have roughly the same epigenetic age in subjects who are younger than 80. These findings suggest that the cerebellum is better protected from aging effects, which in turn could explain why the cerebellum exhibits fewer neuropathological hallmarks of age related dementias compared to other brain regions.

Other

There is research and development of biomarkers of aging, detection systems and software systems to measure biological age of the brain. For example, a deep learning software using anatomic magnetic resonance images estimated brain age with relatively high accuracy, including detecting early signs of Alzheimer's disease and varying neuroanatomical patterns of neurological aging.

Delaying the effects of aging

The current state of biomedical technology does not allow to stop and reverse aging. However, one may potentially delay the effects and severity of its symptoms. While there is no consensus of efficacy, the following are reported as delaying cognitive decline:

Cognitive reserve

The ability of an individual to demonstrate attenuated cognitive signs of aging despite an aging brain is called cognitive reserve. This hypothesis suggests that two patients might have the same brain pathology, with one person experiencing noticeable clinical symptoms, while the other continues to function relatively normally. Studies of cognitive reserve explore the specific biological, genetic and environmental differences which make some people more resistant to cognitive decline than others.

Intellectual quotients derived from psychometric testing have been identified as valuable proxy measures of cognitive reserve, with higher scores relative to the mean being associated with slower rates of cognitive decline. However, the rate of decline in some cognitive subdomains, such as processing speed, may be less affected by premorbid IQ. The degree of association between IQ and cognitive reserve may vary between different types of dementia.

Research

"Super Agers"

Longitudinal research studies have recently conducted genetic analyses of centenarians and their offspring to identify protective factors against the negative effects of aging. In particular, the CETP gene is linked to prevention of cognitive decline and Alzheimer's disease. Specifically, valine CETP homozygotes but not heterozygotes experienced a relative 51% less decline in memory compared to a reference group after adjusting for demographic factors and APOE status.

Nun Study

A study funded by the National Institute on Aging (NIA) began in 1986 and followed a group of 678 Roman Catholic sisters and recorded the effects of aging. The researchers used autobiographical essays collected as the nuns joined their Sisterhood. Findings suggest that early idea density, defined by number of ideas expressed and use of complex prepositions in these essays, was a significant predictor of lower risk for developing Alzheimer's disease in old age. Lower idea density was found to be significantly associated with lower brain weight, higher cerebral atrophy, and more neurofibrillary tangles.

In 1994, Religious Orders Study has begun. Its initial funding was also provided by NIA.

Hypothalamus inflammation and GnRH

In a 2013 study, it was suggested that the inflammation of the hypothalamus may be connected to our overall aging bodies. They focused on the activation of the protein complex NF-κB in mice test subjects, which showed increased activation as mice test subjects aged in the study. This activation not only affects aging, but affects a hormone known as GnRH, which has shown new anti-aging properties when injected into mice outside the hypothalamus, while causing the opposite effect when injected into the hypothalamus. It'll be some time before this can be applied to humans in a meaningful way, as more studies on this pathway are necessary to understand the mechanics of GnRH's anti-aging properties.

Inflammation

A study found that myeloid cells are drivers of a maladaptive inflammation element of brain-ageing in mice and that this can be reversed or prevented via inhibition of their EP2 signalling.

Cerebrospinal fluid

The cerebrospinal fluid circulates in the subarachnoid space around the brain and spinal cord, and in the ventricles of the brain

A study showed that infusing the nourishing cerebrospinal fluid from around brain cells of young mice into aged brains rejuvenates aspects of the brain, proving that it play a role in brain aging and inter alia identifying a protein FGF17 as a key target for potential therapeutics, including for anti-aging.

The subarachnoidal lymphatic-like membrane, whose discovery was reported around 2023, likely plays a role in cerebrospinal fluid functions and, as both a protective barrier and a host of immune cells that monitor the brain for infection and inflammation, appears to be substantially involved in major brain diseases and brain aging. It is "the host for a large population of myeloid cells [(see above)], the number of which increases in response to inflammation and aging".

Aging disparities

For certain demographics, the effects of normal cognitive aging are especially pronounced. Differences in cognitive aging might be tied to the lack of or reduced access to medical care and, as a result, suffer disproportionately from negative health outcomes. As the global population grows, diversifies, and grays, there is an increasing need to understand these inequities.

Race

African Americans

Life expectancy in the USA by race

In the United States, Black and African American demographics disproportionately experience metabolic dysfunction with age. This has many downstream effects, but the most prominent of these is the toll on cardiovascular health. Metabolite profiles of the healthy aging index - a score that assesses neurocognitive function, among other correlates of health through the years - are associated with cardiovascular disease. Healthy cardiovascular function is critical for maintaining neurocognitive efficiency into old age. Attention, verbal learning, and cognitive set ability are related to diastolic blood pressure, triglyceride levels, and HDL cholesterol levels, respectively.

Latinos

In the US, the Latino demographic is most likely to develop metabolic syndrome - the combination of high blood pressure, high blood sugar, elevated triglyceride levels, and abdominal obesity - which not only increases the risk of cardiac events and type 2 diabetes but also is associated with lower neurocognitive function during midlife. This take place even though life expectancy for Latinos in the US is higher than for white and black.

Among different Latin heritages, frequency of the dementia-predisposing ε4 allele of apoE4 gene was highest for Caribbean Latinos (Cubans, Dominicans, Puerto Ricans, 12.6–17.5 %) and lowest among mainland Latinos (Mexicans, Central Americans, and South Americans, 11.0–11.2 %). At the same time, frequency of the neuroprotective ε2 allele was also highest for Caribbean Latinos (5.2–8.6 %) and lowest for those of mainland heritage (2.9–3.9 %). Among mainland Latinos, the most prevalent is the "median" ε3 allele: 85.2–86.2 % compared to 73.9–81.5% among Caribbean Latinos.

Indigenous Peoples

Indigenous populations are often understudied in research. Reviews of current literature studying natives in Australia, Brazil, Canada, and the United States from participants aged 45 to 94 years old reveal varied prevalence rates for cognitive impairment not related to dementia, from 4.4% to 17.7%. These results can be interpreted in the context of culturally biased neurocognitive tests, preexisting health conditions, poor access to healthcare, lower educational attainment, and/or old age.

Sex

Life expectancy in the USA by race and sex, with calculated sex gap

Compared to their male counterparts, women's scores on the mini–mental state examination (MMSE) tend to decline at slightly faster rates with age. Males with mild cognitive impairment tend to show more microstructural damage than females with MCI, but seem to have a greater cognitive reserve due to larger absolute brain size and neuronal density. As a result, women tend to manifest symptoms of cognitive decline at lower thresholds than men do. This effect seems to be moderated by educational attainment - higher education is associated with later diagnosis of mild cognitive impairment as neuropathological load increases. Currently there are no known studies to identify a characteristic pattern of cognitive decline with age in transgender people.

Socioeconomic factors

Socioeconomic status is the interaction between social and economic factors. It has been demonstrated that socio-demographic factors can be used to predict cognitive profiles within older individuals to some extent.  This may be because families of higher socioeconomic status (SES) are equipped to provide their children with resources early on to facilitate cognitive development. For children in families of low SES, relatively small changes in parental income were associated with large changes in brain surface area; these losses were seen in areas associated with language, reading, executive functions, and spatial skills. Meanwhile, for children in families of high SES, small changes in parental income were associated with small changes in surface area within these regions. With respect to global cortical thickness, low SES children showed a curvilinear decrease in thickness with age while those of high SES demonstrated a steeper linear decline, suggesting that synaptic pruning is more efficient in the latter group. This trend was especially evident in the left fusiform and left superior temporal gyri - critical language and literacy supporting areas.

A study showed that 50+ aged users of the dietary program SNAP "had about 2 fewer years of cognitive aging over a 10-year period compared with non-users" despite it having nearly no conditions for the sustainability and healthiness of the food products purchased with the coupons (or coupon-credits).

Entropy (information theory)

From Wikipedia, the free encyclopedia https://en.wikipedia.org/wiki/Entropy_(information_theory) In info...