NAD+ repletion improves mitochondrial and stem cell function and enhances life span in mice

被引：923

作者：

Zhang, Hongbo ^{[1
]}

Ryu, Dongryeol ^{[1
]}

Wu, Yibo ^{[2
]}

Gariani, Karim ^{[1
]}

Wang, Xu ^{[1
]}

Luan, Peiling ^{[1
]}

D'Amico, Davide ^{[1
]}

Ropelle, Eduardo R. ^{[1
,3
]}

Lutolf, Matthias P. ^{[4
]}

Aebersold, Ruedi ^{[2
,5
]}

Schoonjans, Kristina ^{[6
]}

Menzies, Keir J. ^{[1
,7
]}

Auwerx, Johan ^{[1
]}

机构：

[1] Ecole Polytech Fed Lausanne, Lab Integrat & Syst Physiol, CH-1015 Lausanne, Switzerland

[2] ETH, Inst Mol Syst Biol, Dept Biol, CH-8093 Zurich, Switzerland

[3] Univ Estadual Campinas, Sch Appl Sci, Lab Mol Biol Exercise, BR-13484350 Sao Paulo, Brazil

[4] Ecole Polytech Fed Lausanne, Lab Stem Cell Bioengn, CH-1015 Lausanne, Switzerland

[5] Univ Zurich, Fac Sci, CH-8057 Zurich, Switzerland

[6] Ecole Polytech Fed Lausanne, Metab Signaling, CH-1015 Lausanne, Switzerland

[7] Univ Ottawa, Brain & Mind Res Inst, Interdisciplinary Sch Hlth Sci, 451 Smyth Rd, Ottawa, ON K1H 8M5, Canada

来源：

SCIENCE | 2016年 / 352卷 / 6292期

基金：

瑞士国家科学基金会;

关键词：

SKELETAL-MUSCLE; SATELLITE CELLS; METABOLISM; SENESCENCE; ADULT; DIFFERENTIATION; QUIESCENCE; NICHE; REJUVENATION; MAINTENANCE;

D O I：

10.1126/science.aaf2693

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Adult stem cells (SCs) are essential for tissue maintenance and regeneration yet are susceptible to senescence during aging. We demonstrate the importance of the amount of the oxidized form of cellular nicotinamide adenine dinucleotide (NAD(+)) and its effect on mitochondrial activity as a pivotal switch to modulate muscle SC (MuSC) senescence. Treatment with the NAD(+) precursor nicotinamide riboside (NR) induced the mitochondrial unfolded protein response and synthesis of prohibitin proteins, and this rejuvenated MuSCs in aged mice. NR also prevented MuSC senescence in the mdx (C57BL/10ScSn-Dmd(mdx)/J) mouse model of muscular dystrophy. We furthermore demonstrate that NR delays senescence of neural SCs and melanocyte SCs and increases mouse life span. Strategies that conserve cellular NAD(+) may reprogram dysfunctional SCs and improve life span in mammals.

引用

页码：1436 / 1443

页数：8

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