Dietary Restriction, GH/IGF-1 & Mechanisms of Cellular Protection and Regeneration

FOA: PA-20-272现有NIH拨款# P01AG055369的行政补充

FOA: PA-20-272 Administrative Supplements to Existing NIH Grant # P01AG055369 Funded Parent Award: Dietary Restriction, GH/IGF-1 and Mechanisms of Cellular Protection and Regeneration. Abstract Age is the major risk factor for many morbidities including cancer, cardiovascular and neurodegenerative diseases. Biogerontology research is well positioned to help prevent or at least delay these diseases by identifying safe strategies to retard aging so that the degree and type of cellular damage does not reach the threshold leading to disease incidence or progression. Here we propose to study the molecular mechanisms linking fasting, fasting mimicking diets and protein restriction to reduced nutrient signaling, the stress resistance signaling network, the mitochondrial peptide humanin, and in turn, cellular protection, regeneration, and healthspan. An important advantage of the dietary interventions being tested is that they are periodic and therefore have the potential to match and possibly surpass the beneficial effects of chronic calorie restriction while minimizing the burden of chronic and extreme diets, but also while minimizing adverse effects. The common goals are to: 1) identify and study novel periodic dietary interventions that promote healthspan without causing adverse effects at old ages; 2) study the mechanisms of fasting mimicking diet- and protein restriction-dependent cellular protection, regeneration and rejuvenation with focus on the hematopoietic and nervous systems; 3) understand the link between dietary interventions, growth pathways and humanin to test the hypothesis that this mitochondrial peptide functions as a healthspan modulator and determine whether it can serve as a fasting/protein restriction mimetic.