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

FOA：PA-20-272现有NIH补助金的行政补充（编号：P01 AG 055369） 资助父母奖：饮食限制，GH/IGF-1和细胞保护和再生的机制。 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很好地帮助预防或至少延缓这些疾病， 确定延缓衰老的安全策略，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、禁食模仿饮食和蛋白质限制与减少的营养信号联系起来， 信号网络，线粒体肽humanin，反过来，细胞保护，再生， healthspan.正在测试的饮食干预的一个重要优点是，它们是周期性的， 因此有可能达到甚至超过长期热量限制的有益效果 同时最大限度地减少慢性和极端饮食的负担，同时最大限度地减少不良影响。 共同的目标是：1）确定和研究新的周期性饮食干预，促进健康 不会对老年人造成不良影响; 2）研究禁食模仿饮食和蛋白质的机制 限制依赖的细胞保护，再生和再生，重点是造血和 神经系统; 3）了解饮食干预，生长途径和humanin之间的联系，以测试 假设这种线粒体肽作为健康调节剂发挥作用，并确定它是否可以 用作禁食/蛋白质限制模拟物。

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.