Zhang Nannan, Li Zhongchi, Mu Wei, Li Liyuan, Liang Yaru, Lu Maoyang, Wang Zhuoran, Qiu Ying, Wang Zhao
a MOE Key Laboratory of Protein Sciences , Department of Pharmacology, School of Medicine, Tsinghua University , Beijing , P.R. China.
Cell Cycle. 2016;15(7):1009-18. doi: 10.1080/15384101.2016.1152427.
Calorie restriction (CR) extends lifespan from yeast to mammals. SIRT6 is a member of the sirtuin family of NAD(+)-dependent histone deacetylases, which is responsible for mediating the effects of CR. The transcription factor NF-κB, which is involved in inflammation and aging, has been shown to be regulated by SIRT6. Here we describe the crucial role of SIRT6 in aging and inflammation. We show that CR had improved renal insufficiency and enhanced SIRT6 expression after 6-month treatment in aged mice. Culture cells in low glucose (LG) conditions also showed resistance to cell senescence and enhanced SIRT6 expression compared to normal glucose (NG) group, showing beneficial effects of the CR-mimic cultural conditions. Moreover, SIRT6 overexpression is sufficient to delay the replicative senescence of WI38 by attenuating NF-κB signaling, while SIRT6 knockdown results in accelerated cell senescence and overactive NF-κB signaling. These findings confirm the key status of CR and disclose the critical role of SIRT6 on aging and inflammation.
热量限制（CR）可延长从酵母到哺乳动物的寿命。SIRT6是烟酰胺腺嘌呤二核苷酸（NAD⁺）依赖性组蛋白脱乙酰酶的沉默调节蛋白家族的成员，它负责介导热量限制的作用。转录因子NF-κB参与炎症和衰老过程，已被证明受SIRT6调控。在此，我们描述了SIRT6在衰老和炎症中的关键作用。我们发现，在对老年小鼠进行6个月的热量限制治疗后，肾功能不全得到改善，SIRT6表达增强。与正常葡萄糖（NG）组相比，在低葡萄糖（LG）条件下培养的细胞也表现出对细胞衰老的抗性以及SIRT6表达增强，这表明模拟热量限制的培养条件具有有益作用。此外，SIRT6过表达足以通过减弱NF-κB信号传导来延迟WI38细胞的复制性衰老，而敲低SIRT6则导致细胞衰老加速和NF-κB信号传导过度活跃。这些发现证实了热量限制的关键地位，并揭示了SIRT6在衰老和炎症中的关键作用。
