Evolution, mechanism and limits of dietary restriction induced health benefits & longevity

Dietary restriction (DR) is the most powerful intervention to enhance health and lifespan across species. How-ever, recent findings indicate that DR started in late life has limited capacity to induce health benefits. Age-dependent changes that impair DR at old age remain to be delineated. This requires a better mechanistic un-derstanding of the different aspects that constitute DR, how they act independently and in concert. Current research efforts aim to tackle these questions: Are fasting periods needed for the induction of DR's health benefits? Does the improvement of cellular and organismal functions depend on the reduction of specific dietary components like proteins or even micronutrients and/or vitamins? How is the aging process intervening with DR-mediated responses? Understanding the evolutionary benefits of nutrient stress responses in driving molecular and cellular adaptation in response to nutrient deprivation is likely providing answers to some of these questions. Cellular memory of early life may lead to post-reproductive distortions of gene regulatory networks and meta-bolic pathways that inhibit DR-induced stress responses and health benefits when the intervention is started at old age. Inhere we discuss new insights into mechanisms of DR-mediated health benefits and how evolutionary selection for fitness in early life may limit DR-mediated improvements at old age.