Anti-aging medicine: fallacies, realities, imperatives.

AST year's double special sections of the Journal on ''Anti-Aging Medicine'' featured several contributions from the distinguished experimentalist Leonard Hayflick. Among these was '''Anti-Aging' is an Oxymoron,''(1) which ends with a question that clearly lays out the impor- tance of the subject of these issues: since there is an ''almost universal belief by geriatricians that the greatest risk factor for all of the leading causes of death is old age(,) why then are we not devoting significant resources to understanding more about the greatest risk factor for every age-associated pathology by attempting to answer this fundamental ques- tion: 'Why are old cells more vulnerable to pathology than are young cells?''' However pointed Dr. Hayflick's rhetorical question may be, it can only strike its reader as an Herculean non sequitur as a conclusion to this essay. For the thesis of the remainder of the article is that ''No intervention will slow, stop, or reverse the aging process in humans''—indeed, that the very notion of such intervention violates the laws of both logic and physics. If, as Hayflick contends, understanding why old cells are more vulnerable to pathology than are young cells will not allow us to intervene in the process, then understanding aging is a purely curiosity-driven venture of no practical biomedical value—in which case politicians, the publicly-funded research bureaucracy, and the taxpaying public are right to refuse to invest scarce resources into advancing our knowledge in the field. Fortunately, the arguments supporting the ''Oxymoron'' thesis are fundamentally flawed in their logic—and some- times in their representations of experimental data as well. That there is likely to be erroneous argumentation some- where in the article should be clear from the outset to most readers of the Journal, since—in response to Hayflick's challenge that ''When it becomes possible to slow, stop, or reverse the aging process in the simpler molecules that com- pose inanimate objects, such as machines, then that pros- pect may become tenable for the complex molecules that compose life forms''—anyone familiar with the biogeronto- logical literature can readily cite examples in which the latter has already been accomplished in model organisms. The most obvious example is calorie restriction (CR), through which researchers have been intervening in the rate of loss of molecular fidelity and of age-associated acceleration of vulnerability to pathology in mammals for seven decades. As Hayflick—and most readers—must be aware, CR has been robustly documented to retard the accumulation of a wide range of the molecular lesions suspected to underlie aging, and to thereby extend youthful physiological function and species' maximum life span to a degree proportional to the duration and severity of the restriction of energy intake (2)—an effect that appears to be inducible to similar results throughout the life span, including very late in middle age (3). A variety of genetic interventions—primarily based on modulation of signaling by the insulin and insulin-like growth factor-1 axes—also slow down key aspects of bio- logical aging in laboratory rodents (somewhat less certainly) (4) and lower organisms (5,6). Hayflick's conclusion being untenable, we must look to his arguments to see how they fail to lead to it. The present essay is devoted to this task.