ArticlePloS one2011
Hyperactive S6K1 mediates oxidative stress and endothelial dysfunction in aging: inhibition by resveratrol.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 81 papers.
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Who cites it
81 citing papers in PubMed, 156 citations in OpenAlex.
- Angiogenesis in Lung Regeneration and Aging.Arteriosclerosis, thrombosis, and vascular biology · 2026Review
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- Exploiting cellular senescence in hematologic malignancies.Translational oncology · 2026Review
- Cerebellar Abnormalities: A Component of Autism Pathophysiology.Medicina (Kaunas, Lithuania) · 2026Review
- The role of vascular aging, bone marrow and immune system in hypertension.Cell death discovery · 2026Review
- The Janus face of L-arginine supplementation in cardiovascular health and aging exploration of underlying mechanisms.Frontiers in aging · 2026Review
- Deregulation of m6A-RNA methylation impairs adaptive hypertrophic response and drives maladaptation via mTORC1-S6K1-hyperactivation and autophagy impairment.Cell communication and signaling : CCS · 2025Article
- The Role of S6K1 in Aging and Alzheimer's Disease: Mechanistic Insights and Therapeutic Potential.International journal of molecular sciences · 2025Review
- Circular RNA Telomerase Reverses Endothelial Senescence in Progeria.Aging cell · 2025Article
- Effects of aging on immune function and inflammatory biomarkers.American journal of translational research · 2025Article
- The Association between Food Groups, Nutraceuticals, and Food Supplements Consumption on Vascular Health Outcomes: A Literature Review.Life (Basel, Switzerland) · 2024Review
- Vistusertib improves pulmonary inflammation and fibrosis by modulating inflammatory/oxidative stress mediators via suppressing the mTOR signalling.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2024Article
- FLRT2 prevents endothelial cell senescence and vascular aging by regulating the ITGB4/mTORC2/p53 signaling pathway.JCI insight · 2024Article
- Obesity, heart failure with preserved ejection fraction, and the role of glucagon-like peptide-1 receptor agonists.ESC heart failure · 2024Review
- Endothelial cell-specific reduction in mTOR ameliorates age-related arterial and metabolic dysfunction.Aging cell · 2024Article
- Beneficial effects of rapamycin on endothelial function in systemic lupus erythematosus.Frontiers in physiology · 2024Article
- New Dawn for Atherosclerosis: Vascular Endothelial Cell Senescence and Death.International journal of molecular sciences · 2023Review
- Endothelial Senescence and Its Impact on Angiogenesis in Alzheimer's Disease.International journal of molecular sciences · 2023Review
- Article
- Methylglyoxal-Modified Albumin Effects on Endothelial Arginase Enzyme and Vascular Function.Cells · 2023Article
21 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mammalian target of rapamycin (mTOR)/S6K1 signalling emerges as a critical regulator of aging. Yet, a role of mTOR/S6K1 in aging-associated vascular endothelial dysfunction remains unknown. In this study, we investigated the role of S6K1 in aging-associated endothelial dysfunction and effects of the polyphenol resveratrol on S6K1 in aging endothelial cells. We show here that senescent endothelial cells displayed higher S6K1 activity, increased superoxide production and decreased bioactive nitric oxide (NO) levels than young endothelial cells, which is contributed by eNOS uncoupling. Silencing S6K1 in senescent cells reduced superoxide generation and enhanced NO production. Conversely, over-expression of a constitutively active S6K1 mutant in young endothelial cells mimicked endothelial dysfunction of the senescent cells through eNOS uncoupling and induced premature cellular senescence. Like the mTOR/S6K1 inhibitor rapamycin, resveratrol inhibited S6K1 signalling, resulting in decreased superoxide generation and enhanced NO levels in the senescent cells. Consistent with the data from cultured cells, an enhanced S6K1 activity, increased superoxide generation, and decreased bioactive NO levels associated with eNOS uncoupling were also detected in aortas of old WKY rats (aged 20-24 months) as compared to the young animals (1-3 months). Treatment of aortas of old rats with resveratrol or rapamycin inhibited S6K1 activity, oxidative stress, and improved endothelial NO production. Our data demonstrate a causal role of the hyperactive S6K1 in eNOS uncoupling leading to endothelial dysfunction and vascular aging. Resveratrol improves endothelial function in aging, at least in part, through inhibition of S6K1. Targeting S6K1 may thus represent a novel therapeutic approach for aging-associated vascular disease.
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