Department of Pathology, University of Washington, Seattle, WA 98195-7470, USA.
FEBS Lett. 2012 Aug 31;586(18):2868-73. doi: 10.1016/j.febslet.2012.07.038. Epub 2012 Jul 22.
Calorie restriction is reported to enhance survival and delay the onset of age-related decline in many different species. Several proteins have been proposed to play a role in mediating the response to calorie restriction, including the target of rapamycin kinase, sirtuins, and AMP kinase. An enhanced mechanistic understanding of calorie restriction has popularized the concept of "calorie restriction mimetics", drugs that mimic the beneficial effects of caloire restriction without requiring a reduction in nutrient intake. In theory, such drugs should delay the onset and progression of multiple age-related diseases, similar to calorie restriction in mammals. Despite the potential benefits of such calorie restriction mimetics, however, relatively little is known about the interaction between genetic variation and individual response to calorie restriction. Limited evidence from model systems indicates that genotype plays a large role in determining both the magnitude and direction of effect that calorie restriction has on longevity. Here we present an overview of these data from the perspective of using yeast as a model to study aging and describe an approach we are taking to further characterize the molecular mechanisms underlying genotype-dependent responses to calorie restriction.
热量限制被报道能增强许多不同物种的生存能力并延缓与年龄相关的衰退的发生。有几种蛋白质被认为在介导对热量限制的反应中发挥作用，包括雷帕霉素靶蛋白激酶、沉默调节蛋白和 AMP 激酶。对热量限制的机制理解的增强使“热量限制类似物”的概念流行起来，这些药物模仿热量限制的有益效果，而不需要减少营养摄入。从理论上讲，这类热量限制类似物应该能延缓多种与年龄相关疾病的发生和进展，类似于哺乳动物的热量限制。然而，尽管这种热量限制类似物有潜在的好处，但人们对遗传变异与个体对热量限制的反应之间的相互作用知之甚少。来自模型系统的有限证据表明，基因型在很大程度上决定了热量限制对寿命的影响的幅度和方向。在这里，我们从使用酵母作为模型来研究衰老的角度来概述这些数据，并描述了我们正在采取的一种方法，以进一步描述基因型依赖的对热量限制的反应的分子机制。
