Impairment of an Endothelial NAD+-H2S Signaling Network Is a Reversible Cause of Vascular Aging
Name
nihms952930.pdf
Description
Accepted version
Size
2.24 MB
Format
Adobe PDF
Checksum (MD5)
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Author(s)
Das, Abhirup
Huang, George X.
Bonkowski, Michael S.
Longchamp, Alban
Li, Catherine
Schultz, Michael B.
Kim, Lynn-Jee
Osborne, Brenna
Joshi, Sanket
Lu, Yuancheng
Date Issued
March 2018
Journal
Cell
Publisher
Elsevier BV
Citation
Das, Abhirup et al. "Impairment of an Endothelial NAD+-H2S Signaling Network Is a Reversible Cause of Vascular Aging." Cell 173, 1 (March 2018): 74-89 © 2018 Elsevier
Version
Author's final manuscript
Abstract
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. Endothelial SIRT1 regulates pro-angiogenic signals secreted from myocytes and improves muscle health. Treatment of mice with NAD precursor nicotinamide mononucleotide improves vascular and increases endurance in aging mice.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Paul F. Glenn Center for Biology of Aging Research (Massachusetts Institute of Technology)
Terms of Use
Creative Commons Attribution-NonCommercial-NoDerivs License
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DOI of Published Version
https://doi.org/10.1016/j.cell.2018.02.008
