New approaches in aging research

Abstract

Historical milestones in basic research on aging include (1) the demonstration that caloric res-triction (CR) increases average and maximum lifespan in rodents; (2) the proposal that oxidative stress is a major risk factor in the development of age-related pathology; and (3) the demonstration that human fibroblasts grown in culture have a finite lifespan. Thus, although research related to aging has been going on for well over 50 years, particularly on the age-related pathologies associated with aging, serious efforts to understand what factors modulate longevity are fairly new, and progress in this area is due primarily to the identification of genes that modulate longevity in short-lived animal models. Prior to 1980, the main focus was on describing aging phenomena in humans and rodents, and testing the various theories of aging resulting from these early observations. As the techniques of molecular biology were increasingly incorporated into aging-related research, it became possible to ask more mechanistic questions, and considerable progress was made during the period 1980–2000, largely because of the development of short-lived fruit fly and nematode models in which to study aging, followed by the sequencing of the genomes of these organisms. For example, this work quickly led to the discovery that the insulin-signalling pathway plays a major role in modulating longevity, not only in these organisms, but also in rodents and probably primates.