Anderson Rozalyn M, Shanmuganayagam Dhanansayan, Weindruch Richard
Wisconsin National Primate Research Center, Madison, Wisconsin, USA.
Toxicol Pathol. 2009 Jan;37(1):47-51. doi: 10.1177/0192623308329476. Epub 2008 Dec 15.
It is widely accepted that caloric restriction (CR) without malnutrition delays the onset of aging and extends lifespan in diverse animal models including yeast, worms, flies, and laboratory rodents. The mechanism underlying this phenomenon is still unknown. We have hypothesized that a reprogramming of energy metabolism is a key event in the mechanism of CR (Anderson and Weindruch 2007). Data will be presented from studies of mice on CR, the results of which lend support to this hypothesis. Effects of long-term CR (but not short-term CR) on gene expression in white adipose tissue (WAT) are overt. In mice and monkeys, a chronic 30% reduction in energy intake yields a decrease in adiposity of approximately 70%. In mouse epididymal WAT, long-term CR causes overt shifts in the gene expression profile: CR increases the expression of genes involved in energy metabolism (Higami et al. 2004), and it down-regulates the expression of more than 50 pro-inflammatory genes (Higami et al. 2006). Whether aging retardation occurs in primates on CR is unknown. We have been investigating this issue in rhesus monkeys subjected to CR since 1989 and will discuss the current status of this project. A new finding from this project is that CR reduces the rate of age-associated muscle loss (sarcopenia) in monkeys (Colman et al. 2008).
人们普遍认为，在不造成营养不良的情况下进行热量限制（CR），能够延缓衰老的发生，并延长包括酵母、蠕虫、果蝇和实验啮齿动物在内的多种动物模型的寿命。这一现象背后的机制仍然未知。我们推测，能量代谢的重新编程是热量限制机制中的一个关键事件（安德森和魏德鲁克，2007年）。本文将展示对热量限制小鼠的研究数据，其结果支持了这一假设。长期热量限制（而非短期热量限制）对白脂肪组织（WAT）基因表达的影响是明显的。在小鼠和猴子中，能量摄入长期减少30%会使肥胖程度降低约70%。在小鼠附睾脂肪组织中，长期热量限制会导致基因表达谱发生明显变化：热量限制增加了参与能量代谢的基因的表达（日上等，2004年），并下调了50多个促炎基因的表达（日上等，2006年）。热量限制是否能延缓灵长类动物的衰老尚不清楚。自1989年以来，我们一直在对接受热量限制的恒河猴进行这方面的研究，并将讨论该项目的现状。该项目的一项新发现是，热量限制降低了猴子与年龄相关的肌肉流失（肌肉减少症）的速率（科尔曼等人，2008年）。
