NAD+ and sirtuins in aging and disease.

NAD+ and sirtuins in aging and disease.
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DOI:
10.1016/j.tcb.2014.04.002
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发表时间:
2014-08
影响因子:
19
通讯作者:
Guarente, Leonard
Guarente, Leonard
中科院分区:
生物学1区
文献类型:
--
作者:
Imai, Shin-ichiro;Guarente, Leonard

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烟酰胺腺嘌呤二核苷酸 (NAD+) 是介导许多氧化还原反应的经典辅酶。 NAD+ 在 NAD+ 消耗酶的调节中也发挥着重要作用,包括去乙酰化酶、聚 ADP 核糖聚合酶 (PARP) 和 CD38/157 胞外酶。 NAD+ 生物合成,特别是由烟酰胺磷酸核糖基转移酶 (NAMPT) 介导的生物合成和 SIRT1 共同发挥作用,调节新陈代谢和昼夜节律。 NAD+ 水平在衰老过程中下降,可能是一个致命弱点,导致核和线粒体功能缺陷,并导致许多与年龄相关的病症。通过补充 NAD+ 中间体来恢复 NAD+ 可以显着改善这些与年龄相关的功能缺陷,对抗许多衰老疾病,包括神经退行性疾病。因此,激活sirtuin和补充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希望。
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 anti-aging intervention, providing hope to aging societies worldwide.
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