Guarente L
Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
Cold Spring Harb Symp Quant Biol. 2007;72:483-8. doi: 10.1101/sqb.2007.72.024.
Sirtuin genes function as anti-aging genes in yeast, Caenorhabditis elegans, and Drosophila. The NAD requirement for sirtuin function indicates a link between aging and metabolism, and a boost in sirtuin activity may in part explain how calorie restriction extends life span. In mammals, one of the substrates of the SIR2 ortholog, SIRT1, is a regulator of mitochondrial biogenesis, PGC-1alpha. Indeed, the putative SIRT1 activator resveratrol has been shown to stimulate mitochondrial biogenesis and deliver health benefits in treated mice. I explore here how mitochondrial biogenesis may have beneficial effects on aging and, perhaps, diseases of aging. In particular, I speculate that SIRT1-mediated mitochondrial biogenesis may reduce the production of reactive oxygen species, a possible cause of aging, and offer two possible mechanisms for this effect. An understanding of how calorie restriction works may lead to novel drugs to combat diseases of aging.
在酵母、秀丽隐杆线虫和果蝇中，沉默调节蛋白基因发挥着抗衰老基因的作用。沉默调节蛋白发挥功能需要烟酰胺腺嘌呤二核苷酸（NAD），这表明衰老与新陈代谢之间存在联系，而沉默调节蛋白活性的增强可能在一定程度上解释了热量限制是如何延长寿命的。在哺乳动物中，沉默信息调节因子2（SIR2）的直系同源物SIRT1的底物之一是线粒体生物发生的调节因子过氧化物酶体增殖物激活受体γ辅激活因子1α（PGC-1α）。事实上，公认的SIRT1激活剂白藜芦醇已被证明能刺激线粒体生物发生，并给接受治疗的小鼠带来健康益处。在此，我探讨线粒体生物发生如何可能对衰老以及或许对衰老相关疾病产生有益影响。特别地，我推测SIRT1介导的线粒体生物发生可能减少活性氧的产生，活性氧是衰老的一个可能原因，并为此效应提供了两种可能的机制。了解热量限制的作用方式可能会催生对抗衰老相关疾病的新型药物。
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