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

FOA：PA-20-272对现有NIH补助金的行政补充#P01AG055369 资助父母奖：饮食限制、生长激素/胰岛素样生长因子-1和细胞保护与再生机制。 摘要 年龄是许多疾病的主要危险因素，包括癌症、心血管疾病和神经退行性疾病。 疾病。生物老年学研究处于有利地位，可以通过以下方式帮助预防或至少延缓这些疾病 确定安全的策略来延缓衰老，使细胞损伤的程度和类型不会达到 导致疾病发生或进展的阈值。在这里，我们建议研究分子机制。 将禁食、禁食模拟饮食和蛋白质限制与营养信号减少、抗逆性 信号网络，线粒体多肽，人，进而，细胞保护，再生，和 健康跨度。正在测试的饮食干预的一个重要优点是它们是周期性的和 因此有潜力赶上甚至可能超过慢性卡路里限制的有益影响 同时将慢性和极端饮食的负担降至最低，同时还将不良影响降至最低。 共同的目标是：1)确定和研究促进健康的新的周期性饮食干预措施 不会对老年人造成不良影响；2)研究禁食模拟饮食和蛋白质的机制 依赖限制的细胞保护、再生和年轻化，重点是造血和 神经系统；3)了解饮食干预、生长途径和人类激素之间的联系以进行测试 这种线粒体肽作为健康跨度调节器发挥作用的假设，并决定它是否可以 作为禁食/蛋白质限制的模拟物。

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.