Ramsey J J, Harper M E, Weindruch R
Wisconsin Regional Primate Research Center, Madison, WI 53715-1299, USA.
Free Radic Biol Med. 2000 Nov 15;29(10):946-68. doi: 10.1016/s0891-5849(00)00417-2.
Energy restriction (ER), without malnutrition, increases maximum life span and retards the development of a broad array of pathophysiological changes in laboratory rodents. The mechanism responsible for the retardation of aging by ER is, however, unknown. One proposed explanation is a reduction in energy expenditure (EE). Reduced EE may increase life span by decreasing the number of oxygen molecules interacting with mitochondria, thereby lowering reactive oxygen species (ROS) production. As a step toward testing this hypothesis, it is important to determine the effect of ER on EE. Several whole-body, organ, and cellular studies have measured the influence of ER on EE. In general, whole-body studies have reported an acute decrease in mass-adjusted EE that disappears with long-term ER. Organ-specific studies have shown that decreases in EE of liver and gastrointestinal tract are primarily responsible for initial reductions in EE with ER. These data, however, do not determine whether cellular EE is altered with ER. Three major processes contributing to resting EE at the cellular level are mitochondrial proton leak, Na(+)-K(+)-ATPase activity, and protein turnover. Studies suggest that proton leak and Na(+)-K(+)-ATPase activity are decreased with ER, whereas protein turnover is either unchanged or slightly increased with ER. Thus, two of the three major processes contributing to resting EE at the cellular level may be decreased with ER. Although additional cellular measurements are needed, the current results suggest that a lowering of EE could be a mechanism for the action of ER.
在不造成营养不良的情况下，能量限制（ER）可延长实验啮齿动物的最大寿命，并延缓多种病理生理变化的发展。然而，ER延缓衰老的机制尚不清楚。一种提出的解释是能量消耗（EE）减少。EE降低可能通过减少与线粒体相互作用的氧分子数量来延长寿命，从而降低活性氧（ROS）的产生。作为检验这一假设的第一步，确定ER对EE的影响很重要。一些全身、器官和细胞研究测量了ER对EE的影响。一般来说，全身研究报告称，质量调整后的EE会急性下降，但长期ER后这种下降会消失。器官特异性研究表明，肝脏和胃肠道EE的降低是ER导致EE最初降低的主要原因。然而，这些数据并不能确定细胞EE是否会因ER而改变。在细胞水平上，静息EE的三个主要过程是线粒体质子泄漏、Na(+)-K(+)-ATP酶活性和蛋白质周转。研究表明，ER会降低质子泄漏和Na(+)-K(+)-ATP酶活性，而蛋白质周转在ER时要么不变，要么略有增加。因此，在细胞水平上，构成静息EE的三个主要过程中的两个可能会因ER而降低。虽然还需要进行额外的细胞测量，但目前的结果表明，EE降低可能是ER作用的一种机制。
