The mechanism of programmed aging: The way to creation a real remedy for senescence

Nature has sentenced humans to an inevitable death from the time of birth; the natural instrument of execution is the aging process. According to modern scientific notions, only two root causes of aging can be: stochastic physiological damage or the implementation of a special genetic program in the body. The first supposition is dominated from the onset of gerontology to the present day. Indeed, experiments provide conclusive evidence that infections produce toxins, that mitochondria generate ROS which cause mutations in nuclear and mitochondrial DNA, that errors occur in the processes of DNA reduplication, transcription and translation, that lipid peroxidation occurs in membranes, that non-enzymatic glycolysis and crosslinking between molecules occurs, and more; all of this accumulates over time. These facts leave no doubt about the cause of aging and suggest the clear measures to combat it. Almost all experiments aimed at increasing the maximum longevity of animals are reduced ultimately to methods that involve the prevention or restoration of this damage. A lot of different approaches have been tried, but the maximum animal longevity has remained unshakable. These results testify unequivocally that the concept of stochastic physiological damages accumulation is incorrect and therefore the alternative concept of genetically programmed aging is true.

In support of this conclusion, in the last decade, convincing experimental evidence has been found that the aging process is under direct genetic control: dysfunction of a single gene can increase the maximum lifespan of animals (several times for some invertebrates). About 80 such genes have been identified to date. However, this way of prolonging life has proved unsuitable for human due to dangerous side effects. Currently, only unfounded assumptions have been made about the existence of a genetic aging program, but there is no explanation for many empirically discovered phenomena, including this life-extending effect.

A fundamentally new mechanism of programmed aging is presented in this article by Alexander G. Trubitsyn (Institute of Biology, Russian Academy of Sciences). The mechanism of programmed aging has turned out to be much more complicated than that of accumulation of stochastic physiological damages. The destructive stochastic processes that are observed by researchers serve as the mechanism of execution of aging program rather than its root cause which should be fought.

A special bioenergetics aging clock follows from this mechanism of programmed aging and some other empirical data as a logical consequence. This clock gives us an opportunity to clarify nature of the above mentioned empirically found methods of life extending. It is this clock that sets the maximum species-specific longevity. This clock enables us to interpret all discovered phenomena concerning aging and longevity: the nature of the life-lengthening effect under calorie restriction (CR) and numerous CR-mimetic factors. It gives us an opportunity to understand why a bat and a bird lives 10 times longer than a terrestrial animal of a similar size, and a naked mole-rat (Heterocephalus glaber) has an impressively longer longevity in comparison with a home mouse, the nature of negligible senescence of some species and why cancer cells are immortal, and so on.

Most importantly, this special aging clock opens up a fundamentally new way of searching the means to control the aging process. Fundamental research in the field of molecular biology and related areas has already discovered the basic details of this clock, although even the authors of these studies are mostly not aware of the role of their discoveries in the mechanism of programed aging. These data, gathered together, provide insights into the molecular structure and functioning of the bioenergetics aging clock. This makes it possible to outline practical research on the management of the course of this clock, and hence the longevity. Three possible approaches to modify the course of this clock are visible. A creation of actual remedy for senescence in the near future looks like a real possibility.

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