衰老与疾病中的烟酰胺腺嘌呤二核苷酸（NAD+）和沉默调节蛋白
NAD+ and sirtuins in aging and disease.
作者信息
Imai Shin-ichiro, Guarente Leonard
机构信息
Department of Developmental Biology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Glenn Laboratory for the Science of Aging, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
出版信息
Trends Cell Biol. 2014 Aug;24(8):464-71. doi: 10.1016/j.tcb.2014.04.002. Epub 2014 Apr 29.
Nicotinamide adenine dinucleotide (NAD(+)) is a classical coenzyme mediating many redox reactions. NAD(+) also plays an important role in the regulation of NAD(+)-consuming enzymes, including sirtuins, poly-ADP-ribose polymerases (PARPs), and CD38/157 ectoenzymes. NAD(+) biosynthesis, particularly mediated by nicotinamide phosphoribosyltransferase (NAMPT), and SIRT1 function together to regulate metabolism and circadian rhythm. NAD(+) levels decline during the aging process and may be an Achilles' heel, causing defects in nuclear and mitochondrial functions and resulting in many age-associated pathologies. Restoring NAD(+) by supplementing NAD(+) intermediates can dramatically ameliorate these age-associated functional defects, counteracting many diseases of aging, including neurodegenerative diseases. Thus, the combination of sirtuin activation and NAD(+) intermediate supplementation may be an effective antiaging intervention, providing hope to aging societies worldwide.
烟酰胺腺嘌呤二核苷酸（NAD(+)）是一种介导许多氧化还原反应的经典辅酶。NAD(+)在调控消耗NAD(+)的酶（包括沉默调节蛋白、聚ADP核糖聚合酶（PARP）和CD38/157外切酶）方面也发挥着重要作用。NAD(+)生物合成，特别是由烟酰胺磷酸核糖转移酶（NAMPT）介导的生物合成，与SIRT1功能共同调节代谢和昼夜节律。NAD(+)水平在衰老过程中下降，这可能是一个致命弱点，会导致核功能和线粒体功能缺陷，并引发许多与衰老相关的病理状况。通过补充NAD(+)中间体来恢复NAD(+)水平，可以显著改善这些与衰老相关的功能缺陷，对抗包括神经退行性疾病在内的许多衰老相关疾病。因此，激活沉默调节蛋白与补充NAD(+)中间体相结合可能是一种有效的抗衰老干预措施，为全球老龄化社会带来了希望。
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