NAD+激酶
生物
锡尔图因
秀丽隐杆线虫
西妥因1
细胞生物学
长寿
TOR信号
SIRT3
辅因子
信号转导
生物能学
线粒体
转录因子
蛋白质稳态
生物化学
遗传学
酶
下调和上调
基因
作者
Laurent Mouchiroud,Riekelt H. Houtkooper,Norman Moullan,Elena Katsyuba,Dongryeol Ryu,Carles Cantó,Adrienne Mottis,Young-Suk Jo,Mohan Viswanathan,Kristina Schoonjans,Leonard Guarente,Johan Auwerx
出处
期刊:Cell
[Elsevier]
日期:2013-07-01
卷期号:154 (2): 430-441
被引量:940
标识
DOI:10.1016/j.cell.2013.06.016
摘要
NAD(+) is an important cofactor regulating metabolic homeostasis and a rate-limiting substrate for sirtuin deacylases. We show that NAD(+) levels are reduced in aged mice and Caenorhabditis elegans and that decreasing NAD(+) levels results in a further reduction in worm lifespan. Conversely, genetic or pharmacological restoration of NAD(+) prevents age-associated metabolic decline and promotes longevity in worms. These effects are dependent upon the protein deacetylase sir-2.1 and involve the induction of mitonuclear protein imbalance as well as activation of stress signaling via the mitochondrial unfolded protein response (UPR(mt)) and the nuclear translocation and activation of FOXO transcription factor DAF-16. Our data suggest that augmenting mitochondrial stress signaling through the modulation of NAD(+) levels may be a target to improve mitochondrial function and prevent or treat age-associated decline.
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