A Return to Quasi-Programmed and Hyperfunction Views of Aging

Is aging actively selected for by evolutionary processes, a program that provides some advantage to a species, or is aging the polar opposite, the consequence of a lack of selection pressure on late life health? The latter is the present mainstream view of aging, that aging arises because early reproduction is favored by evolution, and thus systems evolve that are initially effective but decline over time. Aging is a side-effect of these maladapted systems, a process called antagonistic pleiotropy.

The ideas put forward by the smaller part of the research community that sees aging as an evolved program are themselves evolving quite rapidly. It is interesting to dip a toe into that water every so often to see where matters stand. At present there is a fair amount of interest in ideas that fall under the heading of quasi-programmed aging, which do not clearly belong to either the traditional programmed aging viewpoints or the antagonistic pleiotropy viewpoints. The hyperfunction view of aging is one of these ideas, in which, to oversimplify, aging is seen as the consequence of developmental programs that continue to run past their useful span of time.

While ruling out programmed aging, evolutionary theory predicts a quasi-program for aging, a continuation of the developmental program that is not turned off, is constantly on, becoming hyper-functional and damaging, causing diseases of aging. Could it be switched off pharmacologically? This would require identification of a molecular target involved in cell senescence, organism aging and diseases of aging. Notably, cell senescence is associated with activation of the TOR (target of rapamycin) nutrient-sensing and mitogen-sensing pathway, which promotes cell growth, even though the cell cycle is blocked.

Is TOR involved in organism aging? In fact, in yeast (where the cell is the organism), caloric restriction, rapamycin, and mutations that inhibit TOR all slow down aging. In animals from worms to mammals caloric restrictions, life-extending agents, and numerous mutations that increase longevity all converge on the TOR pathway. And, in humans, cell hypertrophy, hyper-function and hyperplasia, typically associated with activation of TOR, contribute to diseases of aging. Theoretical and clinical considerations suggest that rapamycin may be effective against atherosclerosis, hypertension and hyper-coagulation (thus, preventing myocardial infarction and stroke), osteoporosis, cancer, autoimmune diseases and arthritis, obesity, diabetes, macular degeneration, Alzheimer's and Parkinson's diseases.

Finally, I discuss that extended life span will reveal new causes for aging (e.g. reactive oxygen species, 'wear and tear', Hayflick limit, stem cell exhaustion) that play a limited role now, when quasi-programmed senescence kills us first.

Link: https://doi.org/10.4161/cc.5.18.3288

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