title: Calorie restriction-induced SIRT6 activation delays aging by suppressing NF-κB signaling.
abstract: 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.
authors.affiliation: a MOE Key Laboratory of Protein Sciences , Department of Pharmacology, School of Medicine, Tsinghua University , Beijing , P.R. China.
authors.forename: Nannan
authors.initials: N
authors.lastname: Zhang
authors.affiliation: a MOE Key Laboratory of Protein Sciences , Department of Pharmacology, School of Medicine, Tsinghua University , Beijing , P.R. China.
authors.forename: Zhongchi
authors.initials: Z
authors.lastname: Li
authors.affiliation: a MOE Key Laboratory of Protein Sciences , Department of Pharmacology, School of Medicine, Tsinghua University , Beijing , P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Mu
authors.affiliation: a MOE Key Laboratory of Protein Sciences , Department of Pharmacology, School of Medicine, Tsinghua University , Beijing , P.R. China.
authors.forename: Liyuan
authors.initials: L
authors.lastname: Li
authors.affiliation: a MOE Key Laboratory of Protein Sciences , Department of Pharmacology, School of Medicine, Tsinghua University , Beijing , P.R. China.
authors.forename: Yaru
authors.initials: Y
authors.lastname: Liang
authors.affiliation: a MOE Key Laboratory of Protein Sciences , Department of Pharmacology, School of Medicine, Tsinghua University , Beijing , P.R. China.
authors.forename: Maoyang
authors.initials: M
authors.lastname: Lu
authors.affiliation: a MOE Key Laboratory of Protein Sciences , Department of Pharmacology, School of Medicine, Tsinghua University , Beijing , P.R. China.
authors.forename: Zhuoran
authors.initials: Z
authors.lastname: Wang
authors.affiliation: a MOE Key Laboratory of Protein Sciences , Department of Pharmacology, School of Medicine, Tsinghua University , Beijing , P.R. China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Qiu
authors.affiliation: a MOE Key Laboratory of Protein Sciences , Department of Pharmacology, School of Medicine, Tsinghua University , Beijing , P.R. China.
authors.forename: Zhao
authors.initials: Z
authors.lastname: Wang
mesh_terms: D000375:Aging; D000818:Animals; D017209:Apoptosis; D031204:Caloric Restriction; D002478:Cells, Cultured; D016922:Cellular Senescence; D004261:DNA Replication; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051437:Renal Insufficiency / Q000517:prevention & control; D015398:Signal Transduction; D037761:Sirtuins / Q000378:metabolism*
chemical_list: D016328:NF-kappa B; C501860:Sirt6 protein, mouse; D037761:Sirtuins
keywords: NF-κB; SIRT6; aging; calorie restriction; inflammation; kidney; p16