Metabolic reprogramming in dietary restriction

Abstract

It is widely accepted that energy intake restriction without essential nutrient deficiency delays the onset of aging and extends life span. The mechanism underlying this phenomenon is still unknown though a number of different, nonmutually exclusive explanations have been proposed. In each of these, different facets of physiology play the more significant role in the mechanism of aging retardation. Some examples include the altered lipid composition model, the immune response model and models describing changes in endocrine function. In this paper we propose the hypothesis that metabolic reprogramming is the key event in the mechanism of dietary restriction, and the physiological effects at the cellular, tissue and organismal level may be understood in terms of this initial event.

Fig. 1

Master regulators respond to DR and induce shifts in metabolism in the restricted organism. These regulators may include the transcriptional coactivator PGC-1α and members of the nuclear receptor family PPAR-α and PPAR-γ. Effectors that respond to the altered metabolic state are involved in tissue-specific changes that ultimately lead to changes at the organismal level, delaying aging and promoting longevity.