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并延长了最长寿命。细胞耗氧量(OC)的减少和氧自由基产生的减少都被认为是ER延缓衰老的重要作用。这些假说可以结合在一起，表明OC的减少可能通过减少与线粒体相互作用的氧分子的数量从而减少自由基的产生来延长寿命。为了验证这一理论，准确地确定ER对整个动物、器官和细胞OC的影响是至关重要的。然而，ER导致细胞OC持续和均匀下降的假设不能通过整体动物研究进行适当的检验。内脏负责超过60%的静息OC，随着ER的增加，几个内脏，特别是肝脏和胃肠道的质量迅速减少。如果不考虑内脏，就不可能从整个动物研究中确定ER是否会导致所有身体成分的OC均匀下降。该项目的目的是确定ER对成年恒河猴器官特异性OC的影响。在这项实验中，我们计划同时测量整个动物和局部(肝肠系膜床、脑和后肢)OC，在留置导管的猴子中生活在量热室中。我们预测ER将导致肝肠系膜OC的快速和持续下降，而脑和后肢的OC将观察到较小或没有变化。在这项使用自由成年恒河猴的研究中，有三个特定的目标：特定的目标1是调整现有的测量局部(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局部OC。具体目标2是确定器官和区域OC对整个动物OC的贡献。具体目标3是通过肝肠系膜床、脑和后肢确定30%ER对OC的影响。这项研究将为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被用来确定长期ER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.