Precedents for the Biological Control of Aging: Experimental Postponement, Prevention, and Reversal of Aging Processes

Abstract

In contemplating the future of aging, it is helpful to recognize that aging postponement, arrest, prevention, and reversal are commonplace but still under-appreciated natural and experimental phenomena. Aging is apparently completely preventable for prolonged periods in many whole animals by nutritional cues that are not confined to calorie restriction. Aging can be substantially postponed by interfering with active life-shortening processes that are triggered by sexual maturation and reproduction in most species, perhaps including humans, but, contrary to the idea that active life shortening is necessitated by a tradeoff against reproduction, aging can also be dramatically postponed by sexual maturation and reproduction (“negative reproductive costs”) in many species, including mammals. Many fundamental age-related changes are actually reversible in adults or adult systems by the application of simple physiological interventions (“segmental aging reversal”). These reversible elemental aspects of aging include, for example, reduced transcription, reduced translation, altered gene expression, reduced DNA repair, reduced mitochondrial function, reduced regenerative capacity, replicative senescence, lipofuscin accumulation, reduced immune function, thymic involution, loss of reproductive cycling in females, age-related organ atrophy, and hair graying and balding. In addition, many aging phenotypes appear to be interlinked, such that correction of one or a few central aging pathways leads to the correction of multiple downstream pathways without the need for specific intervention in any of these dependent pathways. Collectively, such observations reveal aging on multiple levels and in diverse phyla to be driven by biological mechanisms that are considerably more accessible than is classically expected. This body of observations implies that the future of human aging can be substantially different than its past and supports recent excitement over the possibilities of human intervention.