How evolutionary thinking affects people's ideas about aging interventions.

Abstract

Evolutionary theory has guided the development of antiaging interventions in some conscious and some unconscious ways. It is a standard assumption that the body's health has been optimized by natural selection, and that the most benign and promising medical strategies should support the body's efforts to maintain itself. The very concept of natural healing is a reflection of evolutionary thinking about health. Meanwhile, a developing body of experimental evidence points to the startling hypothesis that aging is a metabolic program, under genetic control we are programmed for death. Evolution has provided that the aging program can be abated in times of stress, e.g., caloric restriction. CR mimetics are already recognized as a promising avenue for antiaging research. Beyond this, there are two ancient mechanisms of programmed death in protists that have survived half a billion years of evolution, and still figure in the aging of vertebrates today. These are apoptosis and replicative senescence via telomere truncation. Most researchers have been wary of modifying these mechanisms because they are known to play a stopgap role in cancer prevention. But intriguing evidence suggests that, despite some counter-carcinogenic function, the net result of both these mechanisms may be to shorten lifespan. Thus, interventions that suppress apoptosis and that preserve telomeres may be promising avenues for life extension research. A third element of the body's self-destruction program co-opts the inflammation response. Epidemiological evidence suggests that NSAIDs including aspirin protect against atherosclerosis, arthritis, and some forms of cancer. It may be that aging engages an autoimmune response that can be modified by drugs acting more narrowly on this same pathway. The existence of an evolutionary program that controls aging from the top down supports a new optimism concerning the types of antiaging interventions that are possible, and the likelihood that simple strategies may have dramatic results without dramatic side-effects.