The Updated View Concerning the Possibility of Growing Old Without Senescence

Introduction

B ernard Strehler prophetically said: “There is no inherent property of cells or of metazoan organization which by itself precludes their organization into perpetually functioning and self-replenishing individuals.” ¹ It is clear today that the normal somatic cell lines are potentially immortal, like cancer cells and germ-line cells. ² New findings also paradoxically highlight the capability of old mitochondria, precursor cells, tissues, and organs to rejuvenation during the vital activity at appropriate conditions. ^{3 –7} These and other findings ^{8 –10} can lead to a point at which the age-related changes in the most parts of a body are not the cause but rather the effect of organism's aging. ^2,11 In this connection, “the efforts of evolutionists-gerontologists should probably be directed at clarifying the question of why the organism consisting of potentially immortal cells gets old.” ²

Evolutionary Approach to an Aging Origin

Because antiaging processes can in some cases successfully counteract physiological deterioration, why then in other cases does an organism that is hypothetically composed of potentially nonsenescent parts age? The normal cells do not exist in isolation in the body, and their functions are regulated by out-of-cell factors. The levels and activities of most of these factors are highly dependent on the current response of living beings to external challenges. Evolutionary biology forecasts that organisms always should be adapted in the best way for an ecological niche that is habitual for them.

In fact, most studies of aging are conducted in living beings situated in rather artificial conditions. Such external conditions are less adequate to the evolutionarily adjusted genetic construction of an organism and lead to the appearance of senescence due to incomplete self-maintenance processes. These arguments and some other findings suggest that imitation of appropriate external signals or peculiar modifications of control systems of an organism can lead to the state of full nonsenescence.

The System Approach to an Aging Origin

The system approach application is rather useful for understanding the causes and mechanisms of aging, because the organism represents a supercomplex system consisting of a hierarchy of cooperating subsystems. The functioning of subsystems is subordinated to general purposes and is coordinated and managed by the control systems of the organism. For this reason, an individual functions as a single unit. The steady disturbances in the coordination of the activity of subsystems can result in aging. A.A. Bogdanov, the grandfather of a general theory of systems, identified a “system divergence” (an increasing of subsystems' noncoordination) as the main cause of an aging in the 1920s. It is possible that inadequate interaction of an environment and an organism is the main reason of such noncoordination. Many findings have been published regarding cellular to population levels that are compatible with this approach.

An Environmental Approach to an Aging Origin

It is common knowledge that the influence of all external signals induces organisms to function in one physiological regimen or another. For this reason, the effectiveness of self-maintenance may depend not only on the structural and functional peculiarities of an organism but also indirectly on the signals of the external conditions in which it exists. Exactly as enzyme activity has a bell-shaped dependence on temperature, pH, and so forth, such bell-shaped ¹² and U-shaped ¹³ regularities prevail in nature. Therefore, one can assume that the control systems of a potentially nonsenescent organism are able to sustain a physiological regimen of complete self-maintenance not in any circumstances but only within a certain range of changes in the total external conditions, known as “environmental pressure.” Self-maintenance will be incomplete outside the zone of adequate environmental pressure. The reserve capacity of organism will start to diminish, and it will begin to age. But individuals “strive” to occupy positions in ecological niches with minimal environmental pressure so as to minimize extrinsic mortality and to maximize survivability and life expectancy, despite the onset of senescence, an age-related increase in mortality rate, and decrease in longevity records.

Thus, lowering environmental pressures beyond the critical threshold must result in senescence, which is statistically expressed in an age-related rise in mortality rate. It is worth mentioning that the mortality pattern ^1,11 for populations with a life history that incorporates repeated reproduction is compatible with this concept. The correlation between parameters of mortality statistics for different countries, the populations of which live in varying climatic, social, and economic conditions, is also similar to the mortality pattern for populations of potentially nonsenescent organisms, which age in circumstances preventing, to varying extents, the complete self-maintenance of the organisms.

Concluding Remarks

There are two main and opposite concepts concerning the origin and inevitability of natural senescence. In accordance with the programmed aging similar to the genetic program of development from a zygote to a mature organism, senescence is likewise programmed (e.g., via repression of the telomerase gene) to facilitate the turnover of generations, which is necessary for survival of a population. From the point of view of the stochastic aging, there is no built-in program of senescence; there is only a program of development. After its end, the mature organism could be self-maintained for a limitless time. But the repairing efficiency (e.g., damages from free radicals) must be always less than 100% (in accordance with the accepted postulates).

The interventions based on these concepts fail to extend natural lifespan. ^14,15 I offer a third kind of hypothesis in which emergence of senescence is not a result of the action of a program or stochastic events, but rather is the consequence of functioning in evolutionary and environmentally inadequate conditions. The signals from these habitats induce the incomplete self-maintenance regimen of an organism's control systems as well as the organism itself. Modification of some components of the control system can readjust its parameters, as in the nematode whose lifespan can be prolonged 10-fold in artificial laboratory conditions. ¹⁶ It is possible that a similar result can be attained by means of specific modulation of external signals.