Impairment of an Endothelial NAD+-H2S Signaling Network Is a Reversible Cause of Vascular Aging

被引：398

作者：

Das, Abhirup ^{[1
,2
,3
]}

Huang, George X. ^{[1
,4
]}

Bonkowski, Michael S. ^{[1
]}

Longchamp, Alban ^{[5
]}

Li, Catherine ^{[2
]}

Schultz, Michael B. ^{[1
]}

Kim, Lynn-Jee ^{[2
]}

Osborne, Brenna ^{[6
]}

Joshi, Sanket ^{[6
]}

Lu, Yuancheng ^{[1
]}

Trevino-Villarreal, Jose Humberto ^{[5
]}

Kang, Myung-Jin ^{[2
]}

Hung, Tzong-tyng ^{[7
]}

Lee, Brendan ^{[7
]}

Williams, Eric O. ^{[3
]}

Igarashi, Masaki ^{[3
]}

Mitchell, James R. ^{[5
]}

Wu, Lindsay E. ^{[2
]}

Turner, Nigel ^{[6
]}

Arany, Zolt ^{[4
]}

Guarente, Leonard ^{[3
]}

Sinclair, David A. ^{[1
,2
]}

机构：

[1] Harvard Med Sch, Dept Genet, Paul F Glenn Ctr Biol Mech Aging, Boston, MA 02115 USA

[2] Univ New South Wales, Sch Med Sci, Dept Pharmacol, Lab Ageing Res, Sydney, NSW 2052, Australia

[3] MIT, Dept Biol, Paul F Glenn Ctr Sci Aging Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA

[4] Univ Penn, Perelman Sch Med, Cardiovasc Inst, 3400 Civ Ctr Blvd,Bldg 421, Philadelphia, PA 19104 USA

[5] Harvard TH Chan Sch Publ Hlth, Dept Genet & Complex Dis, Boston, MA USA

[6] Univ New South Wales, Sch Med Sci, Dept Pharmacol, Mitochondrial Bioenerget Lab, Sydney, NSW 2052, Australia

[7] Univ New South Wales, Mark Wainwright Analyt Ctr, Biol Resources Imaging Lab, Sydney, NSW 2052, Australia

来源：

CELL | 2018年 / 173卷 / 01期

基金：

澳大利亚国家健康与医学研究理事会;

关键词：

SKELETAL-MUSCLE CAPILLARIZATION; LIFE-SPAN; NICOTINAMIDE MONONUCLEOTIDE; IMPROVES MITOCHONDRIAL; PREMATURE SENESCENCE; CALORIE RESTRICTION; OXIDATIVE STRESS; AMPK ACTIVATION; SIRT1; EXERCISE;

D O I：

10.1016/j.cell.2018.02.008

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

A decline in capillary density and blood flow with age is a major cause of mortality and morbidity. Understanding why this occurs is key to future gains in human health. NAD precursors reverse aspects of aging, in part, by activating sirtuin deacylases (SIRT1-SIRT7) that mediate the benefits of exercise and dietary restriction (DR). We show that SIRT1 in endothelial cells is a key mediator of pro-angiogenic signals secreted from myocytes. Treatment of mice with the NAD(+) booster nicotinamide mononucleotide (NMN) improves blood flow and increases endurance in elderly mice by promoting SIRT1-dependent increases in capillary density, an effect augmented by exercise or increasing the levels of hydrogen sulfide (H2S), a DR mimetic and regulator of endothelial NAD(+) levels. These findings have implications for improving blood flow to organs and tissues, increasing human performance, and reestablishing a virtuous cycle of mobility in the elderly.

引用

页码：74 / +

页数：36

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