Impairment of an Endothelial NAD + -H 2 S Signaling Network Is a Reversible Cause of Vascular Aging

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 exer...

Full description

Saved in:
Bibliographic Details
Published in:Cell 2018-03, Vol.173 (1), p.74
Main Authors: Das, Abhirup, Huang, George X, Bonkowski, Michael S, Longchamp, Alban, Li, Catherine, Schultz, Michael B, Kim, Lynn-Jee, Osborne, Brenna, Joshi, Sanket, Lu, Yuancheng, Treviño-Villarreal, Jose Humberto, Kang, Myung-Jin, Hung, Tzong-Tyng, Lee, Brendan, Williams, Eric O, Igarashi, Masaki, Mitchell, James R, Wu, Lindsay E, Turner, Nigel, Arany, Zolt, Guarente, Leonard, Sinclair, David A
Format: Article
Language:English
Subjects:
Aging
Animals
Endothelial Cells - cytology
Endothelial Cells - metabolism
Humans
Hydrogen Sulfide - metabolism
Mice
Mice, Knockout
Microvessels - metabolism
Mitochondria - metabolism
Muscle, Skeletal - metabolism
NAD - metabolism
Neovascularization, Physiologic
Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha - metabolism
Physical Conditioning, Animal
Receptors, Notch - metabolism
RNA Interference
RNA, Small Interfering - metabolism
Signal Transduction
Sirtuin 1 - antagonists & inhibitors
Sirtuin 1 - genetics
Sirtuin 1 - metabolism
Vascular Endothelial Growth Factor A - metabolism
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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 (H S), 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.
ISSN:1097-4172