Cited by 496Nitric Oxide and Endothelin EffectsSirtuins and Resveratrol in MedicineSulfur Compounds in Biology

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Impairment of an endothelial NAD(+)-H2S signaling network is a reversible cause of vascular aging

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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.·2018·Cell

DOI 10.1016/j.cell.2018.02.008PMC PMC5884172

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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 (H 2 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.

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InfluentialSelf-citation
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Authors: Das, A., Huang, G. X., Bonkowski, M. S., Longchamp, A., Li, C., Schultz, M. B., Kim, L.-J., Osborne, B., Joshi, S., Lu, Y., Treviño-Villarreal, J. H., Kang, M.-J., Hung, T.-T., Lee, B., Williams, E. O., Igarashi, M., Mitchell, J. R., Wu, L. E., Turner, N., Arany, Z., Guarente, L., & Sinclair, D. A.
Affiliations: Harvard University (US)
UNSW Sydney (AU)
Massachusetts Institute of Technology (US)
Corresponding author: Guarente, Leonard
Sinclair, David A.
ORCID: Das, Abhirup
Huang, George X.
Bonkowski, Michael S.
Longchamp, Alban
Li, Catherine
Osborne, Brenna
Joshi, Sanket
Lu, Yuancheng
Hung, Tzong-tyng
Lee, Brendan
Igarashi, Masaki
Mitchell, James R.
Wu, Lindsay E.
Turner, Nigel
Guarente, Leonard
Sinclair, David A.
Venue: Cell
Publisher: Elsevier BV
Published: 2018-03
Volume: 173
Issue: 1
Pages: 74-89.e20
ISSN: 0092-8674 (ISSN-L)
DOI: 10.1016/j.cell.2018.02.008
PMC: PMC5884172
OpenAlex: W2791288341
Cited by: 496
References: 87
Citations by year: 2026: 41 · 2025: 72 · 2024: 55 · 2023: 65 · 2022: 50 · 2021: 84 · 2020: 64 · 2019: 37 · 2018: 28
FWCI: 36.61
Type: journal article
Language: en
Update notices: erratum (2019-02-07)
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 386 d)
Locations: Cell (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc-nd)
UNSWorks (University of New South Wales, Sydney, Australia) (submittedVersion, cc-by-nc-nd)
Funders: Glenn Foundation for Medical Research (RO1 AG028730, RO1 DK100263)
Sinclair Gift Fund
Edward Schulak (APP1093643)
NIH/NIA (RO1 AG015339)
NIH/NHLBI (RO1 HL094499)
Topics: Health Sciences › Medicine › Physiology (medical) › Nitric Oxide and Endothelin Effects
Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Sulfur Compounds in Biology
Keywords: endothelial cells, NAD+, hydrogen sulfide, vascular aging, blood flow
MeSH terms: Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha, Aging, Animals, Humans, Hydrogen Sulfide, Mitochondria, NAD, Physical Conditioning, Animal, Signal Transduction, Mice, Knockout, Muscle, Skeletal, Neovascularization, Physiologic, RNA Interference, RNA, Small Interfering, Vascular Endothelial Growth Factor A, Endothelial Cells, Mice, Receptors, Notch, Microvessels, Sirtuin 1

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Impairment of an endothelial NAD(+)-H2S signaling network is a reversible cause of vascular aging

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