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Senescence () or biological aging is the gradual deterioration of functional characteristics in living organisms. Whole organism senescence involves an increase in mortality rate or a decrease in fecundity with increasing age, at least in the later part of an organism's life cycle. However, the effects of senescence can be delayed. The 1934 discovery that calorie restriction can Life extension 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 Life extension and thus age-related diseases. Rare human mutations can cause accelerated aging diseases.
Environmental Gerontogens may affect aging – for example, overexposure to ultraviolet radiation accelerates skin aging. Different parts of the body may age at different rates and distinctly, including Aging brain, the cardiovascular system, and muscle. Similarly, functions may distinctly decline with aging, including movement control and memory. Two organisms of the same species can also age at different rates, making biological aging and chronological aging distinct concepts.
Aging is characterized by the declining ability to respond to stress, increased homeostasis imbalance, and increased risk of aging-associated diseases, including cancer and heart disease. Aging has been defined as "a progressive deterioration of physiological function, an intrinsic age-related process of loss of viability and increase in vulnerability."
In 2013, a group of scientists defined nine hallmarks of aging that are common between organisms with emphasis on mammals:
In a decadal update, three hallmarks have been added, totaling 12 proposed hallmarks:
The environment induces damage at various levels, e.g., damage to DNA, and damage to tissues and cells by oxygen radicals (widely known as free radicals), and some of this damage is not repaired and thus accumulates with time. Cloning from rather than germ cells may begin life with a higher initial load of damage. Dolly the sheep died young from a contagious lung disease, but data on an entire population of cloned individuals would be necessary to measure mortality rates and quantify aging.
The evolutionary theorist George Williams wrote, "It is remarkable that after a seemingly miraculous feat of morphogenesis, a complex should be unable to perform the much simpler task of merely maintaining what is already formed."
Almost all organisms senesce, including bacteria which have asymmetries between "mother" and "daughter" cells upon cell division, with the mother cell experiencing aging, while the daughter is rejuvenated. There is negligible senescence in some groups, such as the genus Hydra. Planarian have "apparently limitless telomere regenerative capacity fueled by a population of highly proliferative adult ." These planarians are not biologically immortal, but rather their death rate slowly increases with age. Organisms that are thought to be biologically immortal would, in one instance, be Turritopsis dohrnii, also known as the "immortal jellyfish", due to its ability to revert to its youth when it undergoes stress during adulthood. The reproductive system is observed to remain intact, and even the gonads of Turritopsis dohrnii exist.
Some species exhibit "negative senescence", in which reproduction capability increases or is stable, and mortality falls with age, resulting from the advantages of increased body size during aging.
Theories of aging fall into two broad categories: evolutionary theories of aging and mechanistic theories of aging. Evolutionary theories of aging primarily explain why aging happens, but do not concern themselves with the molecular mechanism(s) that drive the process. All evolutionary theories of aging rest on the basic mechanisms that the force of natural selection declines with age. Mechanistic theories of aging can be divided into theories that propose aging is programmed, and damage accumulation theories, i.e. those that propose aging to be caused by specific molecular changes occurring over time.
The reproductive-cell cycle theory suggests that aging is regulated by changes in hormonal signaling over the lifespan.
There is substantial evidence to back up this theory. Old animals have larger amounts of oxidized proteins, DNA, and lipids than their younger counterparts.
While there may be some validity to the idea that for various types of specific damage detailed below that are by-products of metabolism, all other things being equal, a fast metabolism may reduce lifespan, in general this theory does not adequately explain the differences in lifespan either within, or between, species. Calorically restricted animals process as much, or more, calories per gram of body mass, as their ad libitum fed counterparts, yet exhibit substantially longer lifespans. Similarly, metabolic rate is a poor predictor of lifespan for birds, bats and other species that, it is presumed, have reduced mortality from predation, and therefore have evolved long lifespans even in the presence of very high metabolic rates. In a 2007 analysis it was shown that, when modern statistical methods for correcting for the effects of body size and phylogeny are employed, metabolic rate does not correlate with longevity in mammals or birds.
Concerning specific types of chemical damage caused by metabolism, it is suggested that damage to long-lived , such as structural or DNA, caused by ubiquitous chemical agents in the body such as oxygen and , are in part responsible for aging. The damage can include breakage of biopolymer chains, of biopolymers, or chemical attachment of unnatural substituents () to biopolymers. Under normal conditions, approximately 4% of the oxygen metabolized by mitochondria is converted to superoxide ion, which can subsequently be converted to hydrogen peroxide, hydroxyl radical and eventually other reactive species including other and singlet oxygen, which can, in turn, generate free radicals capable of damaging structural proteins and DNA. Certain metal found in the body, such as copper and iron, may participate in the process. (In Wilson's disease, a genetic disorder that causes the body to retain copper, some of the symptoms resemble accelerated senescence.) These processes termed oxidative stress are linked to the potential benefits of dietary polyphenol , for example in coffee, and green tea. However their typically positive effects on lifespans when consumption is moderate have also been explained by effects on autophagy, glucose metabolism and AMPK.
such as glucose and fructose can react with certain such as lysine and arginine and certain DNA bases such as guanine to produce sugar adducts, in a process called glycation. These adducts can further rearrange to form reactive species, which can then cross-link the structural proteins or DNA to similar biopolymers or other biomolecules such as non-structural proteins. People with diabetes, who have elevated blood sugar, develop senescence-associated disorders much earlier than the general population, but can delay such disorders by rigorous control of their blood sugar levels. There is evidence that sugar damage is linked to oxidant damage in a process termed glycoxidation.
Free radicals can damage proteins, or DNA. Glycation mainly damages proteins. Damaged proteins and lipids accumulate in as lipofuscin. Chemical damage to structural proteins can lead to loss of function; for example, damage to collagen of blood vessel walls can lead to vessel-wall stiffness and, thus, hypertension, and vessel wall thickening and reactive tissue formation (atherosclerosis); similar processes in the kidney can lead to kidney failure. Damage to reduces cellular functionality. Lipid redox of the inner mitochondrial membrane reduces the electric potential and the ability to generate energy. It is probably no accident that nearly all of the so-called "accelerated aging diseases" are due to defective DNA repair enzymes.
It is believed that the impact of alcohol on aging can be partly explained by alcohol's activation of the HPA axis, which stimulates glucocorticoid secretion, long-term exposure to which produces symptoms of aging.
Peter Medawar formalised this observation in his mutation accumulation theory of aging. "The force of natural selection weakens with increasing age—even in a theoretically immortal population, provided only that it is exposed to real hazards of mortality. If a genetic disaster... happens late enough in individual life, its consequences may be completely unimportant". Age-independent hazards such as predation, disease, and accidents, called 'extrinsic mortality', mean that even a population with negligible senescence will have fewer individuals alive in older age groups.
Levels of CD4 and CD8 memory T cells and naive T cells have been used to give good predictions of the expected lifespan of middle-aged mice.
There is research and development of further biomarkers, detection systems, and software systems to measure the biological age of different tissues or systems or overall. For example, a deep learning (DL) software using anatomic magnetic resonance images estimated brain aging with relatively high accuracy, including detecting early signs of Alzheimer's disease and varying neuroanatomical patterns of neurological aging,
and a DL tool was reported as to calculate a person's Inflammaging based on patterns of systemic age-related inflammation.
Aging clocks have been used to evaluate the impacts of interventions on humans, including combination therapies. Employing aging clocks to identify and evaluate longevity interventions represents a fundamental goal in aging biology research. However, achieving this goal requires overcoming numerous challenges and implementing additional validation steps.
Gene expression is imperfectly controlled, and random fluctuations in the expression levels of many genes may contribute to the aging process, as suggested by a study of such genes in yeast. Individual cells, which are genetically identical, nonetheless can have substantially different responses to outside stimuli, and markedly different lifespans, indicating the epigenetic factors play an important role in gene expression and aging as well as genetic factors. There is research into epigenetics of aging.
The ability to repair DNA double-strand breaks declines with aging in mice and humans.
A set of rare hereditary (genetics) disorders, each called progeria, has been known for some time. Sufferers exhibit symptoms resembling accelerated aging, including wrinkle. The cause of Progeria was reported in the journal Nature in May 2003. This report suggests that DNA damage, not oxidative stress, is the cause of this form of accelerated aging.
A study indicates that aging may shift activity toward short genes or shorter transcript length and that this can be countered by interventions.
Biological aging or the LHG comes with a great cost burden to society, including potentially rising health care costs (also depending on types and [[costs of treatments|medical costs]]). This, along with global quality of life or [[wellbeing]], highlight the importance of extending healthspans.
Many measures that may extend lifespans may simultaneously also extend healthspans, albeit that is not necessarily the case, indicating that "lifespan can no longer be the sole parameter of interest" in related research. While recent life expectancy increases were not followed by "parallel" healthspan expansion, awareness of the concept and issues of healthspan lags as of 2017. Scientists have noted that "[Aging-associatedhronic diseases of aging]] are increasing and are inflicting untold costs on human quality of life".
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