Negligible senescence: how will we know it when we see it?

The recent public claim that "SENS is a practical, foreseeable approach to curing aging" has stirred considerable controversy among bio-gerontologists. Testing this hypothesis will not only require precise definitions for the somewhat subjective terms "practical," "foreseeable," and "curing," it will require a precise definition of the term "aging." To facilitate proper experimental design, this definition must focus on the nature of aging itself, not its causes or consequences. Aging in mammals is a process that begins early in adult life and continues steadily thereafter until death. It is manifested by a decline in the functional capacity (or, more precisely, reserve capacity) of a variety of vital physiologic systems leading to increasing risk of morbidity and mortality over time. Aging, however, cannot be measured by simply monitoring morbidity and/or mortality. Aging can only be measured by monitoring the decline of global functional capacity itself. This, in turn, will require an operational definition of aging expressed as a rate function (i.e., it will have units expressing aging as an overall rate of functional change per unit time). Widespread acceptance of such global indexes of aging rate in animal models and humans will greatly facilitate research activity specifically designed to increase the understanding of aging mechanisms and antiaging interventions.