The DOI matches its Crossref record; 86 of the 87 references it cites were found in a registry or an index.
Impairment of an endothelial NAD(+)-H2S signaling network is a reversible cause of vascular aging
Open accessAbstract
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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“NADP boosters (nicotinamide mononucleotide,158 nicotinamide riboside,159 P7C3,160 apigenin161) can be used resolve the NAD depletion issue and are able to prevent senescence in ECs158 and VSMCs.159”
From Senescence-induced inflammation: an important player and key therapeutic target in atherosclerosis (2020) · cites this paper as [158]
In the citing paper
“NMN supplementation also increased the number of endothelial cells and improved endothelial cell function by increasing blood flow and endurance in elderly mice by a SIRT1-dependent mechanism210.”
From NAD+ metabolism and its roles in cellular processes during ageing (2021) · cites this paper as [210]
In the citing paper
“It was reported that premature endothelium senescence reversibly triggers vascular ageing and the age-associated decrease in exercise endurance in old mice [42].”
From Immune Clearance of Senescent Cells to Combat Ageing and Chronic Diseases (2020) · cites this paper as [42]
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Citations
Cites
Calcium's Role in Mechanotransduction during Muscle Development
Damm, T. B., & Egli, M. (2014) · Cellular Physiology and Biochemistry · doi:10.1159/000356667 · Cited by 14,552
Aging: a theory based on free radical and radiation chemistry
Harman, D. (1956) · Journal of Gerontology · doi:10.1093/geronj/11.3.298 · Cited by 8,567 · cited 1×
“A major cause of age-associated endothelial dysfunction is an increase in oxidative stress and apoptosis (Harman, 1956).”
Resveratrol improves health and survival of mice on a high-calorie diet
Baur, J. A., Pearson, K. J., Price, N. L., Jamieson, H. A., Lerin, C., Kalra, A., Prabhu, V. V., Allard, J. S., Lopez-Lluch, G., Lewis, K., et al. (2006) · Nature · doi:10.1038/nature05354 · Cited by 4,290 · cited 2×
“Increasing SIRT1 activity has been thought to improve endurance capacity by increasing mitochondrial function (Bai et al., 2011a, 2011b; Baur et al., 2006; Cantó et al., 2009; Lagouge et al., 2006; Pearson et al., 2008).”
Self-citationLagouge, M., Argmann, C., Gerhart-Hines, Z., Meziane, H., Lerin, C., Daussin, F., Messadeq, N., Milne, J., Lambert, P., Elliott, P., et al. (2006) · Cell · doi:10.1016/j.cell.2006.11.013 · Cited by 4,057 · cited 4×
“Increasing SIRT1 activity has been thought to improve endurance capacity by increasing mitochondrial function (Bai et al., 2011a, 2011b; Baur et al., 2006; Cantó et al., 2009; Lagouge et al., 2006; Pearson et al., 2008).”
InfluentialAMPK regulates energy expenditure by modulating NAD+ metabolism and SIRT1 activity
Cantó, C., Gerhart-Hines, Z., Feige, J. N., Lagouge, M., Noriega, L., Milne, J. C., Elliott, P. J., Puigserver, P., & Auwerx, J. (2009) · Nature · doi:10.1038/nature07813 · Cited by 3,300 · cited 2×
“Increasing SIRT1 activity has been thought to improve endurance capacity by increasing mitochondrial function (Bai et al., 2011a, 2011b; Baur et al., 2006; Cantó et al., 2009; Lagouge et al., 2006; Pearson et al., 2008).”
Transcriptional co-activator PGC-1α drives the formation of slow-twitch muscle fibres
Lin, J., Wu, H., Tarr, P. T., Zhang, C.-Y., Wu, Z., Boss, O., Michael, L. F., Puigserver, P., Isotani, E., Olson, E. N., et al. (2002) · Nature · doi:10.1038/nature00904 · Cited by 2,546 · cited 3×
“Differences in exercise capacity are commonly attributable to changes in muscle fiber type (Pette and Staron, 2000) or mitochondrial content (Lin et al., 2002).”
Mammalian Sirtuins: Biological Insights and Disease Relevance
Haigis, M. C., & Sinclair, D. A. (2010) · Annual Review of Pathology: Mechanisms of Disease · doi:10.1146/annurev.pathol.4.110807.092250 · Cited by 2,085 · cited 2×
“SIRT1 is amember of the sirtuin family of NAD-dependent deacylases that mediate the health benefits of dietary restriction (DR) and can extend lifespan when overexpressed (Guarente, 2013; Haigis and Sinclair, 2010; Kanfi et al., 2012; Satoh et al., 2013).”
Self-citationCantó, C., Menzies, K. J., & Auwerx, J. (2015) · Cell Metabolism · doi:10.1016/j.cmet.2015.05.023 · Cited by 1,648 · cited 2×
“A more recent approach has been to restore NAD levels by treating with NAD precursors such as nicotinamide riboside (NR) or nicotinamide mononucleotide (NMN) (Cantó et al., 2015; Gomes et al., 2013; Mouchiroud et al., 2013; Ramsey et al., 2008).”
Price, N. L., Gomes, A. P., Ling, A. J. Y., Duarte, F. V., Martin-Montalvo, A., North, B. J., Agarwal, B., Ye, L., Ramadori, G., Teodoro, J. S., et al. (2012) · Cell Metabolism · doi:10.1016/j.cmet.2012.04.003 · Cited by 1,602 · cited 6×
“SIRT1-iKO mice were fed tamoxifen (360 mg/kg) diet for five weeks to elicit whole-body SIRT1 exon 4 excision as described previously (Price et al., 2012).”
InfluentialSelf-citationGomes, A. P., Price, N. L., Ling, A. J. Y., Moslehi, J. J., Montgomery, M. K., Rajman, L., White, J. P., Teodoro, J. S., Wrann, C. D., Hubbard, B. P., et al. (2013) · Cell · doi:10.1016/j.cell.2013.11.037 · Cited by 1,482 · cited 8×
“A more recent approach has been to restore NAD+ levels by treating with NAD precursors such as nicotinamide riboside (NR) or nicotinamide mononucleotide (NMN) (Cantó et al., 2015; Gomes et al., 2013; Mouchiroud et al., 2013; Ramsey et al., 2008).”
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Sarcopenia: Aging-Related Loss of Muscle Mass and Function
Larsson, L., Degens, H., Li, M., Salviati, L., Lee, Y. I., Thompson, W., Kirkland, J. L., & Sandri, M. (2019) · Physiological Reviews · doi:10.1152/physrev.00061.2017 · Cited by 1,797
NAD+ metabolism and its roles in cellular processes during ageing
Covarrubias, A. J., Perrone, R., Grozio, A., & Verdin, E. (2021) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-020-00313-x · Cited by 1,617
Modulation of cellular processes by histone and non-histone protein acetylation
Shvedunova, M., & Akhtar, A. (2022) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-021-00441-y · Cited by 1,007
NAD+ in Brain Aging and Neurodegenerative Disorders
Lautrup, S., Sinclair, D. A., Mattson, M. P., & Fang, E. F. (2019) · Cell Metabolism · doi:10.1016/j.cmet.2019.09.001 · Cited by 790
“Mounting evidence supports a critical role for NAD+ in stem cell rejuvenation, including in HSCs, endothelial stem cells, muscle stem cells, and melanocyte stem cells (Das et al., 2018; Vannini et al., 2019; Zhang et al., 2016).”
Self-citationMolecular mechanisms of dietary restriction promoting health and longevity
Green, C. L., Lamming, D. W., & Fontana, L. (2022) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-021-00411-4 · Cited by 714
Metadata
- 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
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2018-03
- Volume
- 173
- Issue
- 1
- Pages
- 74-89.e20
- ISSN
- 0092-8674 (ISSN-L)
- 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
- 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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