At present, the biological basis of ageing is unknown. Most scientists agree that substantial variability exists in the rates of ageing across different species, and that this to a large extent is genetically based. In model organisms and laboratory settings, researchers have been able to demonstrate that selected alterations in specific genes can extend lifespan (quite substantially in nematodes, less so in fruit flies, and even less in mice). Nevertheless, even in the relatively simple organisms, the mechanism of ageing remain to be elucidated. Because the lifespan of even the simple lab mouse is around 3 years, very few experiments directly test specific ageing theories (most of the evidence for the ones listed below is correlative).
The US National Institute on Aging currently funds an intervention testing program, whereby investigators nominate compounds (based on specific molecular ageing theories) to have evaluated with respect to their effects on lifespan and age-related biomarkers in outbred mice.[35] Previous age-related testing in mammals has proved largely irreproducible, because of small numbers of animals, and lax mouse husbandry conditions. The intervention testing program aims to address this by conducting parallel experiments at three internationally recognized mouse ageing-centres, the Barshop Institute at UTHSCSA, the University of Michigan at Ann Arbor and the Jackson Laboratory.
Telomere Theory
Telomeres (structures at the ends of chromosomes) have experimentally been shown to shorten with each successive cell division. Shortened telomeres activate a mechanism that prevents further cell multiplication. This may be an important mechanism of ageing in tissues like bone marrow and the arterial lining where active cell division is necessary. Importantly though, mice lacking telomerase enzyme do not show a dramatically reduced lifespan, as the simplest version of this theory would predict.
Reproductive-Cell Cycle Theory
The idea that ageing is regulated by reproductive hormones that act in an antagonistic pleiotropic manner via cell cycle signalling, promoting growth and development early in life in order to achieve reproduction, but later in life, in a futile attempt to maintain reproduction, become dysregulated and drive senescence (dyosis).
Wear-and-Tear Theory
The very general idea that changes associated with ageing are the result of chance damage that accumulates over time.
****tic Mutation Theory
The biological theory that ageing results from damage to the genetic integrity of the body’s cells.
Error Accumulation Theory
The idea that ageing results from chance events that escape proof reading mechanisms, which gradually damages the genetic code.
The Viral Theory of Ageing
Known causes of cancer (radiation, chemical and viral) account for about 30% of the total cancer burden and for about 30% of the total DNA damage. DNA damage causes the cells to stop dividing or induce apoptosis. DNA damage is thought to be the common pathway causing both cancer and ageing. It seems unlikely that the estimates of the DNA damage due to radiation and chemical causes has been significantly underestimated. Viral infection would appear to be the most likely cause of the other 70% of DNA damage especially in cells that are not exposed to smoking and sun light.[36]
Evolutionary Theories
Enquiry into the evolution of ageing aims to explain why almost all living things weaken and die with age. Exceptions such as rockfish[disambiguation needed], turtles, and naked molerat are highly informative.
Accumulative-Waste Theory
The biological theory of ageing that points to a buildup of cells of waste products that presumably interferes with metabolism.
Autoimmune Theory
The idea that ageing results from an increase in autoantibodies that attack the body's tissues. A number of diseases associated with ageing, such as atrophic gastritis and Hashimoto's thyroiditis, are probably autoimmune in this way. While inflammation is very much evident in old mammals, even SCID mice in SPF colonies still senescence.
Ageing-Clock Theory
The theory that ageing results from a preprogrammed sequence, as in a clock, built into the operation of the nervous or endocrine system of the body. In rapidly dividing cells the shortening of the telomeres would provide just such a clock. This idea is in direct contradiction with the evolutionary based theory of ageing.
Cross-Linkage Theory
The idea that ageing results from accumulation of cross-linked compounds that interfere with normal cell function.
Free-Radical Theory
The idea that free radicals (unstable and highly reactive organic molecules, also named reactive oxygen species or oxidative stress) create damage that gives rise to symptoms we recognize as ageing.
Reliability theory of ageing and longevity
A general theory about systems failure. It allows researchers to predict the age-related failure kinetics for a system of given architecture (reliability structure) and given reliability of its components. Reliability theory predicts that even those systems that are entirely composed of non-ageing elements (with a constant failure rate) will nevertheless deteriorate (fail more often) with age, if these systems are redundant in irreplaceable elements. Ageing, therefore, is a direct consequence of systems redundancy. Reliability theory also predicts the late-life mortality deceleration with subsequent levelling-off, as well as the late-life mortality plateaus, as an inevitable consequence of redundancy exhaustion at extreme old ages. The theory explains why mortality rates increase exponentially with age (the Gompertz law) in many species, by taking into account the initial flaws (defects) in newly formed systems. It also explains why organisms "prefer" to die according to the Gompertz law, while technical devices usually fail according to the Weibull (power) law. Reliability theory allows to specify conditions when organisms die according to the Weibull distribution: organisms should be relatively free of initial flaws and defects. The theory makes it possible to find a general failure law applicable to all adult and extreme old ages, where the Gompertz and the Weibull laws are just special cases of this more general failure law. The theory explains why relative differences in mortality rates of compared populations (within a given species) vanish with age (compensation law of mortality), and mortality convergence is observed due to the exhaustion of initial differences in redundancy levels.
Mitohormesis
It has been known since the 1930s that restricting calories while maintaining adequate amounts of other nutrients can extend lifespan in laboratory animals. Recently, Michael Ristow's group has provided evidence for the theory that this effect is due to increased formation of free radicals within the mitochondria causing a secondary induction of increased antioxidant defence capacity.[37]
Misrepair-Accumulation Theory: This very recent novel theory by Wang et al.[38] suggests that ageing is the result of the accumulation of "Misrepair". Important in this theory is to distinguish among "damage" which means a newly emerging defect BEFORE any reparation has taken place, and "Misrepair" which describes the remaining defective structure AFTER (incorrect) repair. The key points in this theory are:
* There is no original damage left unrepaired in a living being. If damage was left unrepaired a life threatening condition (such as bleeding, infection, or organ failure) would develop.
* Misrepair, the repair with less accuracy, does not happen accidentally. It is a necessary measure of the reparation system to achieve sufficiently quick reparation in situations of serious or repeated damage, to maintain the integrity and basic function of a structure, which is important for the survival of the living being.
* Hence the appearance of Misrepair increases the chance for the survival of individual, by which the individual can live at least up to the reproduction age, which is critically important for the survival of species. Therefore the Misrepair mechanism was selected by nature due to its evolutionary advantage.
* However, since Misrepair as a defective structure is invisible for the reparation system, it accumulates with time and causes gradually the disorganization of a structure (tissue, cell, or molecule); this is the actual source of ageing.
* Ageing hence is the side-effect for survival, but important for species survival. Thus Misrepair might represent the mechanism by which organisms are not programmed to die but to survive (as long as possible), and ageing is just the price to be paid.
[edit] Non-biological theories
Disengagement Theory
This is the idea that separation of older people from active roles in society is normal and appropriate, and benefits both society and older individuals. Disengagement theory, first proposed by Cumming and Henry, has received considerable attention in gerontology, but has been much criticised.[3] The original data on which Cumming and Henry based the theory were from a rather small sample of older adults in Kansas City, and from this select sample Cumming and Henry then took disengagement to be a universal theory.[39] There are research data suggesting that the elderly who do become detached from society as those were initially reclusive individuals, and such disengagement is not purely a response to ageing.[3]
Activity Theory
In contrast to disengagement theory, this theory implies that the more active elderly people are, the more likely they are to be satisfied with life. The view that elderly adults should maintain well-being by keeping active has had a considerable history, and since 1972, this has become to be known as activity theory.[39] However, this theory may be just as inappropriate as disengagement for some people as the current paradigm on the psychology of ageing is that both disengagement theory and activity theory may be optimal for certain people in old age, depending on both circumstances and personality traits of the individual concerned.[3] There are also data which query whether, as activity theory implies, greater social activity is linked with well-being in adulthood.[39]
Selectivity Theory
mediates between Activity and Disengagement Theory, which suggests that it may benefit older people to become more active in some aspects of their lives, more disengaged in others.[39]
Continuity Theory
The view that in ageing people are inclined to maintain, as much as they can, the same habits, personalities, and styles of life that they have developed in earlier years. Continuity theory is Atchley's theory that individuals, in later life, make adaptations to enable them to gain a sense of continuity between the past and the present, and the theory implies that this sense of continuity helps to contribute to well-being in later life.[20] Disengagement theory, activity theory and continuity theory are social theories about ageing, though all may be products of their era rather than a valid, universal theory.
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