DIETARY RESTRICTION AND ENERGY EXPENDITURE

饮食能量限制（ER）改善了大鼠、小鼠和其他动物的健康，延长了最大寿命。细胞耗氧量（OC）的减少和氧自由基产生的减少都被认为在ER延缓衰老中起重要作用。这些假设可能结合起来表明，OC的减少可能通过减少与线粒体相互作用的氧分子数量从而降低自由基的产生来延长寿命。为了验证这一理论，准确确定内质网对整个动物、器官和细胞OC的影响至关重要。然而，内源性雌激素导致细胞OC持续和均匀下降的假设不能通过全动物研究得到适当的验证。内脏器官占静息OC的60%以上，一些内脏器官的质量，特别是肝脏和胃肠道，在ER的作用下迅速减少。如果不考虑内脏器官，就不可能从整个动物研究中确定内源性雌激素是否会导致所有身体成分的OC均匀下降。本项目的目的是确定雌激素对成年恒河猴器官特异性OC的影响。在本实验中，我们计划同时测量全动物和局部（肝肠系膜床、脑和后肢）的OC。我们预测ER将导致肝肠系膜床OC快速持续下降，而脑和后肢OC的变化较小或没有变化。在这项使用无约束成年恒河猴的研究中，有三个具体目标：具体目标1是改进现有的测量区域（肝肠系膜床、脑和后肢）和整个动物OC的系统，以允许同时测量整个动物和区域OC。具体目标2是确定器官和区域脂肪含量对整个动物脂肪含量的贡献。具体目的3是确定30% ER对肝肠系膜床、脑和后肢OC的影响。本研究将为研究ER对成年灵长类动物局部OC的影响提供重要的新信息。所提出的方法可能最终用于确定长期内源性雌激素是否导致组织OC的均匀减少。

Dietary energy restriction (ER) improves health and increase maximum life span in rats, mice, and other animals. A decrease in cellular oxygen consumption (OC) and a reduction in oxygen free radical production have both been proposed to play an important role in the retardation of aging by ER. These hypotheses may be combined to suggest that a reduction in OC may increase life span by decreasing the number of oxygen molecules interacting with the mitochondria and thus lowering free radical production. To test this theory, it is crucial that the effects of ER on whole animal, organ, and cellular OC are accurately determined. The hypothesis that ER causes a sustained and uniform decrease in cellular OC, however, can not be properly tested by whole animal studies. The internal organs are responsible for greater than 60 percent of resting OC and the mass of several internal organs, especially liver and gastrointestinal tract, are rapidly decreased with ER. Without accounting for the internal organs, it is impossible to determine from whole animal studies if ER causes a uniform decrease in OC by all body components. The goal of this proposed project is to determine the effect of ER on organ specific OC in adult rhesus monkeys. In this experiment, we plan to simultaneously measure whole animal and regional (hepatomesenteric bed, brain, and hindlimb) OC in catheterized monkeys living in calorimetry chambers. We predict that ER will result in a rapid and sustained decrease in hepatomesenteric bed OC, while smaller or no changes in OC will be obeserved in brain and hindlimb. In this study using unrestrained adult rhesus monkeys, there are three specific aims: Specific Aim 1 is to adapt current systems for measuring regional (hepatomesenteric bed, brain, and hindlimb) and whole animal OC to allow simultaneous measurement of whole animal and regional OC. Specific Aim 2 is to determine the contribution of organ and regional OC to whole animal OC. Specific Aim 3 is to determine the effect of a 30 percent ER on OC by the hepatomesenteric bed, brain, and hindlimb. This study will provide important new information about the effect of ER on regional OC in an adult primate. The proposed methods may ultimately be used to determine if long-term ER causes a uniform reduction in tissue OC.