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.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“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]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
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).”
InfluentialSelf-citation
Flagged first, then by citations
1 of the 87 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Items 101–200 of 496
Vascular dysfunction as a potential culprit of sarcopenia
Jeon, Y. K., Shin, M. J., Saini, S. K., Custodero, C., Aggarwal, M., Anton, S. D., Leeuwenburgh, C., & Mankowski, R. T. (2021) · Experimental Gerontology · doi:10.1016/j.exger.2020.111220 · Cited by 60
Cellular Senescence Affects Cardiac Regeneration and Repair in Ischemic Heart Disease
Yan, C., Xu, Z.-M., & Huang, W. (2021) · Aging and Disease · doi:10.14336/ad.2020.0811 · Cited by 61
Hydrogen sulfide in ageing, longevity and disease
Wilkie, S. E., Borland, G., Carter, R. N., Morton, N. M., & Selman, C. (2021) · Biochemical Journal · doi:10.1042/bcj20210517 · Cited by 58
Li, X., Wu, G., Han, F., Wang, K., Bai, X., Jia, Y., Li, Z., Cai, W., Zhang, W., Su, L., et al. (2018) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2018.11.016 · Cited by 57
Zhang, Y.-J., Zhang, M., Zhao, X., Shi, K., Ye, M., Tian, J., Guan, S., Ying, W., & Qu, X. (2020) · Basic Research in Cardiology · doi:10.1007/s00395-020-0817-z · Cited by 56
Sun, X., & Feinberg, M. W. (2021) · Frontiers in Physiology · doi:10.3389/fphys.2021.693067 · Cited by 56
Petrovic, D., Slade, L., Paikopoulos, Y., D’Andrea, D., Savic, N., Stančić, A., Miljković, J. L., Vignane, T., Drekolia, M. K., Mladenović, D. R., et al. (2025) · Cell Metabolism · doi:10.1016/j.cmet.2024.12.008 · Cited by 56
Epigenetic Regulation of Vascular Aging and Age-Related Vascular Diseases
Ding, Y.-N., Tang, X., Chen, H., & Liu, D. (2018) · Advances in experimental medicine and biology · doi:10.1007/978-981-13-1117-8_4 · Cited by 55
CD38 in the age of COVID-19: a medical perspective
Horenstein, A. L., Faini, A. C., & Malavasi, F. (2021) · Physiological Reviews · doi:10.1152/physrev.00046.2020 · Cited by 53
Exercise improves vascular health: Role of mitochondria
Zhang, X., & Gao, F. (2021) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2021.11.002 · Cited by 52
Pencina, K. M., Lavu, S., dos Santos, M. R., Beleva, Y. M., Cheng, M. S., Livingston, D. H., & Bhasin, S. (2022) · The Journals of Gerontology Series A · doi:10.1093/gerona/glac049 · Cited by 54
Poljšak, B., Kovač, V., Špalj, S., & Milisav, I. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24032959 · Cited by 56
Gulej, R., Nyúl‐Tóth, Á., Csík, B., Petersen, B., Faakye, J., Negri, S., Chandragiri, S. S., Mukli, P., Yabluchanskiy, A., Conley, S. M., et al. (2023) · GeroScience · doi:10.1007/s11357-023-01039-2 · Cited by 51
“…production of reactive oxygen species (ROS) [24, 55, 57–66], compromised nitric oxide availability [10, 17–19], cellular NAD + depletion [35, 67–69], epigenetic alterations (including sirtuin dysregulation) [58, 70], and energetic dysfunctions [36] implicated in the etiology of vascular aging…”
Hydrogen sulfide signaling in regulation of cell behaviors
Wang, Y., Yu, R., Wu, L., & Yang, G. (2020) · Nitric Oxide · doi:10.1016/j.niox.2020.07.002 · Cited by 50
Self-citationKiss, T., Nyúl‐Tóth, Á., Gulej, R., Tarantini, S., Csípő, T., Mukli, P., Ungvari, A., Balasubramanian, P., Yabluchanskiy, A., Benyó, Z., et al. (2022) · GeroScience · doi:10.1007/s11357-022-00519-1 · Cited by 48
Three-dimensional-cultured MSC-derived exosome with hydrogel for cerebral ischemia repair
Han, M., Zhang, Z., Liu, Z., Liu, Y., Zhao, H., Wang, B., Zhang, C., Shang, H., Li, Y., Wang, S., et al. (2023) · Biomaterials Advances · doi:10.1016/j.bioadv.2023.213396 · Cited by 50
Pharmacology and Potential Implications of Nicotinamide Adenine Dinucleotide Precursors
She, J., Sheng, R., & Qin, Z. (2021) · Aging and Disease · doi:10.14336/ad.2021.0523 · Cited by 50
Neuroinflammation as a mechanism linking hypertension with the increased risk of Alzheimer’s disease
Klegeris, A., & Bajwa, E. (2022) · Neural Regeneration Research · doi:10.4103/1673-5374.336869 · Cited by 49
“Age-related dysfunction of mitophagy contributes to the development of neurological, as well as cardiovascular, diseases, including endothelial damage, atherosclerosis, and hypertension (Das et al., 2018; Fang and Tao, 2020; Morciano et al., 2020).”
Role of hydrogen sulfide in cardiovascular ageing
Testai, L., Citi, V., Martelli, A., Brogi, S., & Calderone, V. (2020) · Pharmacological Research · doi:10.1016/j.phrs.2020.105125 · Cited by 49
Pencina, K. M., Valderrábano, R. J., Wipper, B., Orkaby, A. R., Reid, K. F., Storer, T. W., Lin, A. P., Merugumala, S. K., Wilson, L. A., Latham, N. K., et al. (2023) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgad027 · Cited by 48
Self-citationRole of oxidative stress in the process of vascular remodeling following coronary revascularization
Gallo, G., Pierelli, G., Forte, M., Coluccia, R., Volpe, M., & Rubattu, S. D. (2018) · International Journal of Cardiology · doi:10.1016/j.ijcard.2018.05.046 · Cited by 47
A review of the mechanism of action of Dantonic® for the treatment of chronic stable angina
Liao, W., Ma, X., Li, J., Li, X., Guo, Z., Zhou, S., & Sun, H. (2018) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2018.10.013 · Cited by 46
Common Pathogenetic Mechanisms Underlying Aging and Tumor and Means of Interventions
Shen, W., He, J., Hou, T., Si, J., & Chen, S. (2022) · Aging and Disease · doi:10.14336/ad.2021.1208 · Cited by 45
Discovery of a Redox Thiol Switch: Implications for Cellular Energy Metabolism
Gao, X., Li, L., Parisien, M., Mcleod, M., Wu, J., Bederman, I., Gao, Z., Krokowski, D., Abbott, D. W., Diatchenko, L., et al. (2020) · Molecular & Cellular Proteomics · doi:10.1074/mcp.ra119.001910 · Cited by 50
Mitochondrial Contributions to Hematopoietic Stem Cell Aging
Morganti, C., & Ito, K. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms222011117 · Cited by 50
Nicotinamide Adenine Dinucleotide in Aging Biology: Potential Applications and Many Unknowns
Bhasin, S., Seals, D. R., Migaud, M. E., Musi, N., & Baur, J. A. (2023) · Endocrine Reviews · doi:10.1210/endrev/bnad019 · Cited by 50
Icariin enhances youth-like features by attenuating the declined gut microbiota in the aged mice
Li, X., Khan, I., Xia, W., Huang, G., Liu, L., Law, B. Y. K., Yin, L., Liao, W., Leong, W., Han, R., et al. (2021) · Pharmacological Research · doi:10.1016/j.phrs.2021.105587 · Cited by 46
Self-citationThe Role of SGLT2 Inhibitors in Vascular Aging
Liu, L., Ni, Y., Zhan, J., & Liu, Y. (2021) · Aging and Disease · doi:10.14336/ad.2020.1229 · Cited by 44
“Sirtuin 1 (SIRT1) is highly expressed in ECs, and a vital regulator of vascular remodeling in response to vascular endothelial growth factor (VEGF)-stimulated angiogenesis [25].”
BackgroundAnthracycline chemotherapy‐mediated vascular dysfunction as a model of accelerated vascular aging
Clayton, Z. S., Hutton, D. A., Mahoney, S. A., & Seals, D. R. (2021) · Aging and Cancer · doi:10.1002/aac2.12033 · Cited by 44
A systematic review and meta-analysis of the SIRT1 response to exercise
Juan, C. G., Matchett, K. B., & Davison, G. W. (2023) · Scientific Reports · doi:10.1038/s41598-023-38843-x · Cited by 45
Zhang, H., Zhou, W., Wang, H., Zhang, J., Yang, H., Chen, J., Wang, S., Zhao, W., Li, M., & Luo, Z. Y. (2025) · ACS Nano · doi:10.1021/acsnano.5c01134 · Cited by 47
Endothelial Cell Mechano-Metabolomic Coupling to Disease States in the Lung Microvasculature
Wu, D., & Birukov, K. G. (2019) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2019.00172 · Cited by 46
“SIRT1 is a key mediator of angiogenesis (Das et al., 2018) and stimulates endothelial NOS activity (Mattagajasingh et al., 2007).”
BackgroundLuo, X., Bai, Y., He, S., Sun, S., Jiang, X., Yang, Z., Lu, D., Wei, P., Liang, Y., Peng, C., et al. (2021) · Cell Proliferation · doi:10.1111/cpr.12991 · Cited by 42
Host–microbiome interactions in nicotinamide mononucleotide (NMN) deamidation
Kim, L., Chalmers, T. J., Madawala, R. J., Smith, G. C., Li, C., Das, A., Poon, E. W. K., Wang, J., Tucker, S. P., Sinclair, D. A., et al. (2023) · FEBS Letters · doi:10.1002/1873-3468.14698 · Cited by 45
Self-citationAdelnia, F., Cameron, D., Bergeron, C. M., Fishbein, K. W., Spencer, R. G. S., Reiter, D. A., & Ferrucci, L. (2019) · Frontiers in Physiology · doi:10.3389/fphys.2019.00427 · Cited by 41
“…in arterial function (Behnke and Delp, 2010; Ward et al., 2018), endothelial dysfunction and/or impairment of the endothelial NAD+-H2S signaling network with aging (Das et al., 2018) and a decline in the number of capillaries in aging muscle (Urbieta-Caceres et al., 2012; Bigler et al., 2016).”
BackgroundHydrogen sulfide in longevity and pathologies: Inconsistency is malodorous
Sokolov, A. S., Nekrasov, P. V., Shaposhnikov, M. V., & Moskalev, A. (2021) · Ageing Research Reviews · doi:10.1016/j.arr.2021.101262 · Cited by 42
Rotondo, R., Proietti, S., Marzia Perluigi, A., Padua, E., Stocchi, F., Fini, M., Stocchi, V., Volpe, D., & Pandis, M. F. D. (2023) · Ageing Research Reviews · doi:10.1016/j.arr.2023.102089 · Cited by 44
Hydrogen sulfide and hepatic lipid metabolism – a critical pairing for liver health
Loiselle, J. J., Yang, G., & Wu, L. (2018) · British Journal of Pharmacology · doi:10.1111/bph.14556 · Cited by 40
“Notably, garlic oil attenuated ethanol-induced hepatic steatosis in both mice and human cell line models (Zeng et al., 2012) and increased intracellular H2S levels in HEK cells (when cysteine or GSH was present) (DeLeon et al., 2016).”
BackgroundSelf-citationArsiwala, T., Pahla, J., van Tits, L. J., Bisceglie, L., Gaul, D. S., Costantino, S., Miranda, M. X., Nussbaum, K., Stivala, S., Błyszczuk, P., et al. (2020) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2020.01.002 · Cited by 40
The regulation of healthspan and lifespan by dietary amino acids
Babygirija, R., & Lamming, D. W. (2021) · Translational Medicine of Aging · doi:10.1016/j.tma.2021.05.001 · Cited by 43
Fernández, J., Fernández‐Sanjurjo, M., Iglesias‐Gutiérrez, E., Martínez‐Camblor, P., Villar, C. J., Tomás‐Zapico, C., Fernández‐Garcia, B., & Lombó, F. (2021) · Frontiers in Physiology · doi:10.3389/fphys.2021.748854 · Cited by 40
Maintenance of NAD+ Homeostasis in Skeletal Muscle during Aging and Exercise
Ji, L. L., & Yeo, D. (2022) · Cells · doi:10.3390/cells11040710 · Cited by 44
Vascular Dementia: From Pathophysiology to Therapeutic Frontiers
Yang, H. (2025) · Journal of Clinical Medicine · doi:10.3390/jcm14186611 · Cited by 48
“Preclinical research shows that NAD+ precursors NMN and NR protect blood vessels through their ability to boost endothelial function and reduce inflammation [151].”
Emerging pharmacological tools to control hydrogen sulfide signaling in critical illness
Marutani, E., & Ichinose, F. (2020) · Intensive Care Medicine Experimental · doi:10.1186/s40635-020-0296-4 · Cited by 39
SIRT3 is required for liver regeneration but not for the beneficial effect of nicotinamide riboside
Mukherjee, S., Mo, J., Paolella, L. M., Perry, C. E., Toth, J., Hugo, M., Chu, Q., Tong, Q., Chellappa, K., & Baur, J. A. (2021) · JCI Insight · doi:10.1172/jci.insight.147193 · Cited by 40
The metabolite alpha-ketobutyrate extends lifespan by promoting peroxisomal function in C. elegans
Wu, N., Ma, Y., Gong, X.-Q., Zhao, P., Jia, Y.-J., Zhao, Q., Duan, J.-H., & Zou, C. (2023) · Nature Communications · doi:10.1038/s41467-023-35899-1 · Cited by 41
Gulej, R., Nyúl‐Tóth, Á., Csík, B., Patai, R., Petersen, B., Negri, S., Chandragiri, S. S., Shanmugarama, S., Mukli, P., Yabluchanskiy, A., et al. (2024) · GeroScience · doi:10.1007/s11357-024-01154-8 · Cited by 39
“…on cell-autonomous mechanisms [73, 74], such as mitochondrial dysfunction [75, 76], increased reactive oxygen species production [26, 74, 77–86] and related impairment in NO bioavailability [10, 17–19], cellular NAD + depletion [87–90], epigenetic changes [78, 91], and energetic dysfunctions [75].”
Ahmed, M., Riaz, U., Lv, H., Amjad, M., Ahmed, S., Ali, S., Ghani, M. U., Hua, G., & Yang, L. (2024) · Antioxidants · doi:10.3390/antiox14010039 · Cited by 38
“This intervention may also mitigate age-related declines in NAD + levels across multiple organs [5,20,38,42].”
Effects of aging, hypertension and diabetes on the mouse brain and heart vasculomes
Guo, S., Deng, W., Xing, C., Zhou, Y., Ning, M., & Lo, E. H. (2018) · Neurobiology of Disease · doi:10.1016/j.nbd.2018.07.021 · Cited by 38
SIRT1 in Secretory Organ Cancer
Frazzi, R. (2018) · Frontiers in Endocrinology · doi:10.3389/fendo.2018.00569 · Cited by 38
Role of amino acid metabolism in angiogenesis
Oberkersch, R. E., & Santoro, M. M. (2018) · Vascular Pharmacology · doi:10.1016/j.vph.2018.11.001 · Cited by 38
Youngson, N. A., Uddin, G. M., Das, A., Martinez, C., Connaughton, H. S., Whiting, S., Yu, J., Sinclair, D. A., Aitken, R. J., & Morris, M. J. (2019) · Reproduction · doi:10.1530/rep-18-0574 · Cited by 38
“In this experiment, NMN was administered through drinking water at a slightly reduced dose (chronic rather than acute), which has nonetheless been shown to have beneficial effects on improving muscle blood vessel density and endurance in mice (Das et al. 2018).”
InfluentialSelf-citationLi, X., Li, N., Huang, L., Xu, S. J., Zheng, X. Y., Hamsath, A., Zhang, M., Dai, L., Zhang, H., Wong, J. J. L., et al. (2020) · Frontiers in Oncology · doi:10.3389/fonc.2020.00234 · Cited by 38
Caloric restriction mimetics for the treatment of cardiovascular diseases
Sciarretta, S., Forte, M., Castoldi, F., Frati, G., Versaci, F., Sadoshima, J., Kroemer, G., & Maiuri, M. C. (2020) · Cardiovascular Research · doi:10.1093/cvr/cvaa297 · Cited by 39
Endothelial SIRT1 as a Target for the Prevention of Arterial Aging: Promises and Challenges
Begum, M. K., Konja, D., Singh, S., Chłopicki, S., & Wang, Y. (2021) · Journal of Cardiovascular Pharmacology · doi:10.1097/fjc.0000000000001154 · Cited by 40
Current Uncertainties and Future Challenges Regarding NAD+ Boosting Strategies
Poljšak, B., Kovač, V., & Milisav, I. (2022) · Antioxidants · doi:10.3390/antiox11091637 · Cited by 42
Innovations in Geroscience to enhance mobility in older adults
Anton, S. D., Cruz‐Almeida, Y., Singh, A., Alpert, J. M., Bensadon, B. A., Cabrera, M., Clark, D. J., Ebner, N. C., Esser, K. A., Fillingim, R. B., et al. (2020) · Experimental Gerontology · doi:10.1016/j.exger.2020.111123 · Cited by 40
“Given the NAD metabolome destabilizes with age (Das et al., 2018), supplementation with NR has been shown to stabilize the NAD metabolome in a variety of tissues (Yoshino et al., 2018).”
BackgroundJhanji, M., Rao, C. N., & Sajish, M. (2020) · GeroScience · doi:10.1007/s11357-020-00295-w · Cited by 37
Poffé, C., Robberechts, R., Thienen, R. V., & Hespel, P. (2023) · The Journal of Physiology · doi:10.1113/jp284346 · Cited by 35
Sirtuins family as a target in endothelial cell dysfunction: implications for vascular ageing
Zhang, H., Dai, Y., Zhang, C., Alfred, M. O., Ghosh, A., Khanra, I., Chakraborty, M., Yu, X., & Liang, J. L. (2020) · Biogerontology · doi:10.1007/s10522-020-09873-z · Cited by 35
Immunometabolic Status of COVID-19 Cancer Patients
Sica, A., Colombo, M. P., Trama, A., Horn, L., Garassino, M. C., & Torri, V. (2020) · Physiological Reviews · doi:10.1152/physrev.00018.2020 · Cited by 35
“Of relevance, the NAD / SIRT1 system also guarantees the production of hydrogen sulfide (H2S), which acts as an endothelial signaling network that ensures vascular wellness (19).”
BackgroundSIRT6 in Vascular Diseases, from Bench to Bedside
Ren, S., Chen, X., Gong, H., Wang, H., Wu, C. F., Li, P., Chen, X., Qu, J.-H., & Tang, X. (2022) · Aging and Disease · doi:10.14336/ad.2021.1204 · Cited by 35
Role and Potential Mechanisms of Nicotinamide Mononucleotide in Aging
Rahman, S. U., Qadeer, A., & Wu, Z. (2024) · Aging and disease · doi:10.14336/ad.2023.0519-1 · Cited by 34
Wang, J., Liu, L., Ding, Z. J., Luo, Q., Ju, Y., & Song, G. (2021) · Antioxidants · doi:10.3390/antiox10020254 · Cited by 35
Targeting NAD Metabolism for the Therapy of Age-Related Neurodegenerative Diseases
Li, F., Wu, C., & Wang, G. (2023) · Neuroscience Bulletin · doi:10.1007/s12264-023-01072-3 · Cited by 37
“[89, 90] the elevation of SIRT1 protein expression/activity, and the SIRT3-dependent global decrease in mitochondrial protein acetylation [68, 107–110].”
BackgroundChen, X., Wang, H., Wu, C. F., Li, X., Huang, X., Ren, Y., Pu, Q., Cao, Z., Tang, X., & Ding, B. (2024) · Redox Biology · doi:10.1016/j.redox.2024.103038 · Cited by 33
“H 2 S is a critical oxidant scavenger ameliorating vascular metabolic stress and vascular adaptation [52,54 – 56], which may rely on the activation effects of H 2 S on AMPK [52,53].”
BackgroundPreventing Developmental Origins of Cardiovascular Disease: Hydrogen Sulfide as a Potential Target?
Hsu, C., & Tain, Y. (2021) · Antioxidants · doi:10.3390/antiox10020247 · Cited by 34
RETRACTED ARTICLE: The Na/K-ATPase Oxidant Amplification Loop Regulates Aging
Sodhi, K., Nichols, A., Mallick, A., Klug, R. L., Liu, J., Wang, X., Srikanthan, K., Goguet-Rubio, P., Nawab, A., Pratt, R. D., et al. (2018) · Scientific Reports · doi:10.1038/s41598-018-26768-9 · Cited by 32
RetractedLuo, G., Xiao, L., Wang, D., Wang, N., Luo, C., Yang, X., & Hao, L. (2020) · Toxicology in Vitro · doi:10.1016/j.tiv.2020.104808 · Cited by 34
Ageing and longevity genes in cardiovascular diseases
Liberale, L., Kraler, S. C., Camici, G. G., & Lüscher, T. F. (2020) · Basic & Clinical Pharmacology & Toxicology · doi:10.1111/bcpt.13426 · Cited by 34
Jiang, T., Yang, W., Zhang, H., Song, Z., Liu, T., & Lv, X. (2020) · Frontiers in Physiology · doi:10.3389/fphys.2020.00596 · Cited by 32
“(3) Inhibition of SIRT1 abolished SIRT1-dependent Nrf2/HO1 and eNOS activation, thus enhancing oxidative stress, inflammation, and apoptosis.”
BackgroundDai, Q., Fan, X., Meng, X., Sun, S., Su, Y., Ling, X., Chen, X., Wang, K., Dai, X., Zhang, C., et al. (2021) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.16369 · Cited by 33
Tian, Y., Zhu, C., Li, P., Li, H., Liu, Q., Deng, X., & Wang, J. (2022) · Journal of Surgical Research · doi:10.1016/j.jss.2022.09.030 · Cited by 32
Wang, W., Ren, S., Lu, Y., Chen, X. X., Qu, J., Ma, X., Deng, Q., Hu, Z., Jin, Y. J., Zhou, Z., et al. (2021) · The EMBO Journal · doi:10.15252/embj.2020106771 · Cited by 30
Self-citationFrom Microcirculation to Aging-Related Diseases: A Focus on Endothelial SIRT1
Law, M., Wang, P., Zhou, Z.-Y., & Wang, Y. (2024) · Pharmaceuticals · doi:10.3390/ph17111495 · Cited by 35
Epigenetic modifications and emerging therapeutic targets in cardiovascular aging and diseases
Qiu, Y., Xu, Q., Xie, P., He, C., Li, Q., Yao, X., Mao, Y. H., Wu, X., & Zhang, T. (2024) · Pharmacological Research · doi:10.1016/j.phrs.2024.107546 · Cited by 33
Sirt1 coordinates with ERα to regulate autophagy and adiposity
Tao, Z., Shi, L., Parke, J., Zheng, L., Gu, W. J., Dong, X. C., Liu, D., Wang, Z., Olumi, A. F., & Cheng, Z. (2021) · Cell Death Discovery · doi:10.1038/s41420-021-00438-8 · Cited by 32
Multi-Modal Regulation of Circadian Physiology by Interactive Features of Biological Clocks
Lee, Y., & Wisor, J. P. (2021) · Biology · doi:10.3390/biology11010021 · Cited by 35
New insights into vascular aging: Emerging role of mitochondria function
Li, Y., Jin, X., Li, D. X., Lu, J. Z., Zhang, X., Yang, S., Zhao, Y., & Wu, M. (2022) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2022.113954 · Cited by 30
Erol, İ., Çiğerci, İ. H., Özkara, A., Akyıl, D., & Aksu, M. (2022) · Journal of Biomaterials Science Polymer Edition · doi:10.1080/09205063.2022.2046986 · Cited by 29
NAD+ supplementation limits triple-negative breast cancer metastasis via SIRT1-P66Shc signaling
Jiang, Y., Luo, Z., Gong, Y., Fu, Y., & Luo, Y. (2023) · Oncogene · doi:10.1038/s41388-023-02592-y · Cited by 29
Endothelial Senescence and Its Impact on Angiogenesis in Alzheimer’s Disease
Georgieva, I., Tchekalarova, J. D., Iliev, D. B., & Tzoneva, R. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241411344 · Cited by 29
Mitophagy modulation for the treatment of cardiovascular diseases
Forte, M., D’Ambrosio, L., Schiattarella, G. G., Salerno, N., Perrone, M. A., Loffredo, F. S., Bertero, E., Pilichou, K., Manno, G., Valenti, V., et al. (2024) · European Journal of Clinical Investigation · doi:10.1111/eci.14199 · Cited by 29
“NAD + supplementation with exogenous precursors exerts beneficial effects in models of ageing and CVDs. 45,46 Mechanistically, NAD + stimulates mitophagy by activating the protein deacetylase sirtuins.”
BackgroundChen, G., An, N., Ye, W., Huang, S., Chen, Y., Hu, Z., Shen, E., Zhu, J., Gong, W., Tong, G., et al. (2021) · Redox Biology · doi:10.1016/j.redox.2021.101904 · Cited by 29
“Cell migration was determined using the wound healing scratch assay as previously described [36].”
MethodEndothelial metabolism in pulmonary vascular homeostasis and acute respiratory distress syndrome
Stevens, R. P., Paudel, S. S., Johnson, S., Stevens, T., & Lee, J. (2021) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.00131.2021 · Cited by 32
Disrupted Binding of Cystathionine γ-Lyase to p53 Promotes Endothelial Senescence
Hu, J., Leisegang, M. S., Looso, M., Drekolia, M.-K., Wittig, J., Mettner, J., Karantanou, C., Kyselova, A., Dumbović, G., Li, X., et al. (2023) · Circulation Research · doi:10.1161/circresaha.123.323084 · Cited by 29
Endothelial dysfunction in the aging kidney
Borri, M., Jacobs, M. E., Carmeliet, P., Rabelink, T. J., & Dumas, S. J. (2025) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.00287.2024 · Cited by 31
Gulej, R., Patai, R., Ungvari, A., Kállai, A., Tarantini, S., Yabluchanskiy, A., Huffman, D. M., Conboy, M. J., Conboy, I. M., Mika Kivimaki, B., et al. (2025) · GeroScience · doi:10.1007/s11357-025-01657-y · Cited by 29
Jiang, T., Liu, Y., Meng, Q., Lv, X., Yue, Z., Ding, W., Liu, T., & Cui, X. (2019) · Surgery · doi:10.1016/j.surg.2018.12.018 · Cited by 28
Swaminathan, A., Fokin, A., Venckūnas, T., & Degens, H. (2021) · Scientific Reports · doi:10.1038/s41598-021-81037-6 · Cited by 28
Endothelial mTOR maintains hematopoiesis during aging
Ramalingam, P., Poulos, M. G., Gutkin, M. C., Katsnelson, L., Freire, A. G., Lazzari, E., & Butler, J. M. (2020) · The Journal of Experimental Medicine · doi:10.1084/jem.20191212 · Cited by 27
Kim, Y.-M., Sanborn, M. A., Vijeth, S., Gajwani, P., Wang, X., Jung, D., Vályi-Nagy, T., Chakraborty, S., Mancinelli, G. E., Tóth, P. T., et al. (2025) · Nature Cancer · doi:10.1038/s43018-025-00975-6 · Cited by 28
Translational geroscience: From invertebrate models to companion animal and human interventions
Lee, M. B., & Kaeberlein, M. R. (2018) · Translational Medicine of Aging · doi:10.1016/j.tma.2018.08.002 · Cited by 28
Wu, G., Guo, Y., Li, M., Li, C., Tan, Y., Li, Y., Li, J., Wang, L., Zhang, X., & Gao, F. (2022) · Cells · doi:10.3390/cells11101706 · Cited by 28
“Endurance exercise ability was measured as previously described [28].”
MethodSelf-citationPeng, J., Zhou, Y., Zhang, H., Wu, Y., Cai, A., Mao, X., Deng, Z., Yang, Y., Song, T., Xiong, J., et al. (2018) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2018.11.003 · Cited by 27
DNA Break-Induced Epigenetic Drift as a Cause of Mammalian AgingPreprint
Hayano, M., Yang, J.-H., Bonkowski, M. S., Amorim, J. A., Ross, J. M., Coppotelli, G., Griffin, P. T., Chew, Y. C., Guo, W., Yang, X., et al. (2019) · SSRN Electronic Journal · doi:10.2139/ssrn.3466338 · Cited by 27
Self-citationNAD+ and Vascular Dysfunction: From Mechanisms to Therapeutic Opportunities
Abdellatif, M., Bugger, H., Kroemer, G., & Sedej, S. (2022) · Journal of Lipid and Atherosclerosis · doi:10.12997/jla.2022.11.2.111 · Cited by 26
H2S Protects from Rotenone-Induced Ferroptosis by Stabilizing Fe-S Clusters in Rat Cardiac Cells
Linjacki, S., Wang, Y., Baath, N., Mantle, D., & Yang, G. (2024) · Cells · doi:10.3390/cells13050371 · Cited by 26
Advancements in NMN biotherapy and research updates in the field of digestive system diseases
Liao, G., Xie, Y., Peng, H., Li, T., Zou, X., Yue, F., Guo, J., & Rong, L. (2024) · Journal of Translational Medicine · doi:10.1186/s12967-024-05614-9 · Cited by 27
H2S to Mitigate Vascular Aging: A SIRT1 Connection
Arumugam, T. V., & Kennedy, B. K. (2018) · Cell · doi:10.1016/j.cell.2018.03.011 · Cited by 27
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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
