Ageing theories

Author:

F. M. Burnet, R. Walford.

History:

In 1950-60s F. M. Burnet proposed the first postulates of the immunological theory. Then this theory was developed by R. Walford and other scientists.

Example:

As we age, immune function declines. As the result, in elderly age the risk of autoimmune pathologies (in this case, the immune system does not recognise structures of the own organism) increases.

Description of the Theory:

According to the immunological theory, the immune system is programmed to decline its functions over time, and this fact is the main cause of aging.

The immune system has several important functions. It detects and destroys a wide variety of alien agents, and distinguish them from the organism’s own healthy cells and tissues, which are preserved from destruction. The efficiency of the immune system reaches the peak in the puberty, and then it gradually decreases. Thymic involution (shrinking of the thymus with age) is believed to be the main age-related change in the immune system, and this alteration begins after puberty.

In most elderly people, immunosenescence is characterized by decreased resistance to infectious diseases and decreased protection against cancer. As the result, the risk of death becomes significantly higher in elderly age. Nowadays, death caused by such infections as pneumonia, influenza, nephritis and sepsis are on the first place among the main causes of death of people over 65 years old.

Last years, lots of intense scientific researches are held which can enhance immune function in elderly people, and as the result, slow down the process of aging. One of the directions of such researches — creation of the immune system cells using methods of genetic engineering — is developed by G. Pawelec, J. Macleod, A. Thomson. Another direction is the development of methods that allow delaying thymic involution. This direction is developed by G. Sempowski, A. N. Devallejo, v. Dixit.

Additions and Сriticism:

Up to date, the immunological theory has a lot of open questions. Particularly, there is no consensus about the supreme cause of the immune system senescence. Moreover, although the role of the immune system in aging processes is established, purely immune mechanism of aging is doubtful. The immunological theory is merging with neuroendocrine and free radical theories of aging.

Publications:

• Fulop, Tamas, et al. «On the immunological theory of aging." (2014): 163–176.
• Franceschi, Claudio, et al. «The immunology of exceptional individuals: the lesson of centenarians." Immunology today 16.1 (1995): 12–16.
• George, Andrew JT, and Mary A. Ritter. «Thymic involution with ageing: obsolescence or good housekeeping?» Immunology today 17.6 (1996): 267–272.
• Daynes, R. A., and B. A. Araneo. «Prevention and reversal of some age-associated changes in immunologic responses by supplemental dehydroepiandrosterone sulfate therapy." Aging, immunology and infectious disease 3.3 (1992): 135–154.

Author:

P. Medawar

History:

This theory was proposed in 1952. Medawar’s theory was written in response to, and as an alternative for, A. Weismann’s earlier programmed death theory.

Example:

A strong, active, good-looking individual who has genes associated with Alzheimer’s disease or cancer, has a chance to die earlier in an old age, but to leave more numerous descendants.

Description of the Theory:

The sense of the theory is following: genes with harmful mutations exhibiting in old age does not meet any significant resistance of the natural selection, thereby mutations in such genes accumulate and cause aging. According to the mutation accumulation theory, genes useful in early life of an individual (e.g. genes involving in reproduction) are supporting by the natural selection in contrast to genes useful in old age (e.g. genes reducing the risk of oncological or neurodegenerative diseases).

Thus just the young generation, not the old one makes the main contribution in the creation of new generations. The author of the mutation accumulation theory relied on the fact that any population experiences hunger, drought, predator pressure, diseases and accidents, therefore, frequently, the cause of death is random injuries. Hence P. Medawar concluded that old individuals are too scanty in nature that they cannot impact on the genepool of the population neither in favour of aging not against it. The mutation accumulation theory demonstrates non-adaptive nature of aging as well as absence of special genes which cause «programmed aging». P. Medawar showed that changes an organism undergoes after reproductive age have no value for evolu

tion. While harmful mutations showing its effects in youth meet tough resistance of the natural selection due to negative effect on reproductive fitness, the similar mutations showing its effects in old age are comparatively neutral as their carriers have already given their own genes to descendants. 

Additions and Сriticism:

Restricted field of use. The mutation accumulation theory implies that an individual lives in very aggressive and unstable environment when even a small difference in qualities important for survival (e.g. speed and strength) may be useful.
If there is enough resources, no predator and if the environment is quite stable, elderly individuals will be able to leave descendants. Thus the natural selection will advantage the genes associated with longevity.
These critical notes result in the emergence of the antagonistic pleiotropy theory.

Existence of organisms with «acute» programmed death. There is a number of diverse organisms (e.g. salmon, octopus, marsupial mouse, and bamboo) which display instances of death closely following an act of sexual reproduction. Death in these species appears to be controlled by the reproductive function or controlled by whatever triggers reproduction as opposed to calendar age.

Mutations influence mainly the active genes. Therefore, accumulation of mutations in active genes only will affect the process of aging. That means these genes’ activity is associated with aging and beyond the reproductive period. The evolution assists in keeping these genes' activity in old age, and if the mutagenesis in such genes is weak, these genes will probably be able to play a positive role in the health maintenance in a senescent organism.

Resume:

It is necessary to supplement the mutation accumulation theory with other theories of aging such as the antagonistic pleiotropy theory.

Publications:

• Medawar PB: An Unsolved Problem of Biology. London, HK Lewis, 1952.
• Charlesworth B: Fisher, Medawar, Hamilton and the evolution of aging. Genetics 2000; 156:927–931.
• Charlesworth B: Evolution in Age-Structured Populations. Cambridge, Cambridge University Press, 4. Gavrilova NS, Gavrilov LA, Evdokushkina GN, Semyonova VG, Gavrilova AL, Evdokushkina NN, Kushnareva YE, Kroutko VN, Andreyev AY: Evolution, mutation, and human longevity: European royal and noble families. Hum Biol 1998;70:799–804.
• Strehler BL: Origin and comparison of the effects of time and high energy radiations on living systems. Quart Rev Biol 1959;34:117- 142.