The University of Birmingham, Edgbaston, UK.
Exp Gerontol. 2010 Jun;45(6):395-9. doi: 10.1016/j.exger.2010.03.006. Epub 2010 Mar 10.
A common biochemical characteristic of aging is proteotoxicity i.e. the accumulation of altered proteins. While many studies have shown that NAD(+) is important when lifespan is modulated by dietary means, it is uncertain whether or how NAD(+) affects either formation or elimination of altered proteins. It is suggested here that changes in NAD(+) availability can affect generation of methylglyoxal (MG) from glycolytic intermediates, which in turn can damage proteins, promote generation of reactive oxygen species and induce mitochondrial dysfunction. The proposal can also help to explain how, by altering NAD(+) regeneration from NADH, dietary supplementation with glycerol or glucose, which decreases lifespan in the nematode Caenorhabditis elegans, could cause MG generation to increase, whereas oxaloacetate supplementation, which increases lifespan, could lower the potential for MG formation. The proposal also suggests how upregulation of mitogenesis and mitochondrial activity, and increased aerobic activity, help to decrease the potential for MG formation and resultant proteotoxicity, with consequential beneficial effects with respect to aging.
衰老的一个常见生化特征是蛋白毒性，即异常蛋白的积累。虽然许多研究表明，当寿命通过饮食方式进行调节时，NAD(+) 很重要，但尚不确定 NAD(+) 是否以及如何影响异常蛋白的形成或消除。这里提出的观点是，NAD(+) 供应的变化会影响糖酵解中间产物生成甲基乙二醛 (MG)，这反过来又会损害蛋白质，促进活性氧的生成并诱导线粒体功能障碍。该建议还可以帮助解释为什么通过改变 NADH 向 NAD(+) 的再生，甘油或葡萄糖的饮食补充会导致秀丽隐杆线虫寿命缩短，因为 MG 的生成增加，而补充草酰乙酸可增加 MG 形成的潜力。该建议还表明，细胞有丝分裂和线粒体活性的上调以及有氧活动的增加如何有助于降低 MG 形成的潜力和由此产生的蛋白毒性，从而对衰老产生有益的影响。
