Factors that affect the translation of dietary restriction into a longer life

Nutritional interventions, such as dietary or calorie restriction, are known to have a variety of health-promoting effects. The most impressive are the direct effects on life expectancy, which have been reproduced in many animal models. A variety of dietary restriction protocols have been described, which differ either in their macronutrient composition or in the time window for consumption. Mechanistically, the effects of dietary restriction are mediated mainly through signaling pathways that have central roles in the maintenance of cellular energy balance. Among these, target of rapamycin and insulin signaling appear to be the most important. Such nutritional interventions can have their effects in two different ways: either by direct interaction with the metabolism of the host organism, or by modulating the composition and performance of its endogenous microbiome. Various dietary restriction regimens have been identified that significantly alter the microbiome and thus profoundly modulate host metabolism. This review aims to discuss the mechanisms by which dietary restriction can affect life expectancy, and in particular the role of the microbiome.