ENERGY BALANCE AND METABOLISM

项目2的核心假设，能量平衡和代谢，是饮食限制（DR） 通过改变能量和底物代谢来延长寿命。DR是唯一已知的 持续增加寿命的环境干预。因为有一个惊人的关系 在啮齿类动物中，热量限制的水平和寿命延长的幅度之间， 代谢是探索灵长类动物中DR作用的基本追求。因此，我们建议 继续在这方面努力，并确定了以下具体目标。这些都是为了表征 年龄和DR对以下方面的独立和交互影响： 1.身体成分到最精细的水平可分辨; 2.底物代谢的多个方面，包括能量消耗和葡萄糖稳态。 还将评估身体组成对这些结果的影响; 3.脂肪组织的生物活性。 到目前为止，我们已经记录了慢性病风险因素的显着减少，包括减少 肥胖、维持无脂肪质量、改善胰岛素敏感性和不存在2型糖尿病。 在接下来的五年里，我们将利用PPG动物来测试DR将 增加健康寿命，最终延长寿命，如减少脂肪量和代谢率所示， 维持无脂肪质量、骨骼肌质量和胰岛素敏感性。一个关联假设是， DR的作用将通过脂肪组织信号的变化来介导。

The central hypothesis of Project 2, Energy Balance and Metabolism, is that dietary restriction (DR) increases longevity through changes in energy and substrate metabolism. DR is the only known environmental intervention that consistently increases life span. Because there is a striking relationship between the level of caloric restriction and the magnitude of life extension in rodents, the study of energy metabolism is a fundamental pursuit for probing the actions of DR in primates. Accordingly, we propose to continue our pursuits in this area and have identified the following specific aims. These are to characterize the independent and interactive effects of age and DR on: 1. Body composition to the finest level resolvable; 2. Multiple facets of substrate metabolism, including energy expenditure and glucose homeostasis. effects of body composition on these outcomes will also be evaluated; 3. The bioactivity of adipose tissue. To date, we have documented significant reductions in chronic disease risk factors including decreased obesity, maintenance of fat-free mass, improved insulin sensitivity, and absence of type 2 diabetes. During the coming five years, we will utilize the PPG animals to test the general hypotheses that DR will increase health span and, eventually life span, as displayed by reduced fat mass and metabolic rate, and maintenance of fat-free mass, skeletal muscle mass, and insulin sensitivity. A linking hypothesis is that the effects of DR will be mediated through changes in adipose tissue signals.