热量限制通过降低NADH水平来延长酵母的寿命。
Calorie restriction extends yeast life span by lowering the level of NADH.
作者信息
Lin Su-Ju, Ford Ethan, Haigis Marcia, Liszt Greg, Guarente Leonard
机构信息
Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
出版信息
Genes Dev. 2004 Jan 1;18(1):12-6. doi: 10.1101/gad.1164804.
Abstract
Calorie restriction (CR) extends life span in a wide variety of species. Previously, we showed that calorie restriction increases the replicative life span in yeast by activating Sir2, a highly conserved NAD-dependent deacetylase. Here we test whether CR activates Sir2 by increasing the NAD/NADH ratio or by regulating the level of nicotinamide, a known inhibitor of Sir2. We show that CR decreases NADH levels, and that NADH is a competitive inhibitor of Sir2. A genetic intervention that specifically decreases NADH levels increases life span, validating the model that NADH regulates yeast longevity in response to CR.
摘要
热量限制（CR）可延长多种物种的寿命。此前，我们发现热量限制通过激活Sir2（一种高度保守的依赖NAD的脱乙酰酶）来增加酵母的复制寿命。在此，我们测试热量限制是通过提高NAD/NADH比值还是通过调节烟酰胺（一种已知的Sir2抑制剂）水平来激活Sir2。我们发现热量限制会降低NADH水平，且NADH是Sir2的竞争性抑制剂。一种专门降低NADH水平的基因干预可延长寿命，这验证了NADH响应热量限制调节酵母寿命的模型。
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