ArticleEMBO molecular medicine2021
Glomerular endothelial cell senescence drives age-related kidney disease through PAI-1.
Article in EMBO molecular medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 71 citations in OpenAlex.
- Mechanometabolic endothelial senescence as a translational framework for cardiometabolic vascular disease and vascular ageing.Molecular biology reports · 2026Review
- Vascular aging as a driver of organ dysfunction and systemic aging.Nature cardiovascular research · 2026Review
- Article
- NAMPT activation uncovers a senescence-specific vulnerability and promotes healthy aging in combination with NAM.bioRxiv : the preprint server for biology · 2026Article
- Molecular mechanisms and therapeutic strategies of glomerular cell senescence in diabetic kidney disease: from heterogeneity to precision intervention.Cellular and molecular life sciences : CMLS · 2026Review
- General Anaesthesia Versus Conscious Sedation in Transcatheter Aortic Valve Implantation: Differences in Pulmonary Infections.Reviews in cardiovascular medicine · 2026Article
- The Aging Kidney and Acute Kidney Injury.Journal of the American Society of Nephrology : JASN · 2026Review
- Review
- Functional Molecular Plasma Biomarkers of Inflammation and Repair in Kidney Disease Progression in Gum Arabica Modality of CKD.International journal of molecular sciences · 2026Article
- Virus-induced endothelial senescence as a cause and driving factor for ME/CFS and long COVID: mediated by a dysfunctional immune system.Cell death & disease · 2026Review
- PAI-1: A Key Signal at the Crossroads of Stem Cell Differentiation and Senescence.International journal of molecular sciences · 2025Review
- SUL-138 mitigates accelerated endothelial aging and protects the kidney.Clinical science (London, England : 1979) · 2025Article
- Late-Life Aerobic Exercise Attenuates DNA Damage and Telomere Dysfunction in Non-Atheroprone but Not in Atheroprone Aortic Regions.Aging cell · 2025Article
- Cells of all trades - on the importance of spatial positioning of senescent cells in development, healing and aging.FEBS letters · 2025Review
- Update of cellular senescence in kidney fibrosis: from mechanism to potential interventions.Frontiers of medicine · 2025Review
- Antioxidant Senotherapy by Natural Compounds: A Beneficial Partner in Cancer Treatment.Antioxidants (Basel, Switzerland) · 2025Review
- Nicotinamide mononucleotide restores impaired metabolism, endothelial cell proliferation and angiogenesis in old sedentary male mice.iScience · 2025Article
- The interplay between endothelial cell dysfunction and podocyte injury in diabetic nephropathy: a comprehensive review of current evidence.American journal of translational research · 2025Review
- Mechanisms of cellular senescence-induced vascular aging: evidence of senotherapeutic strategies.The journal of cardiovascular aging · 2025Article
- FOXO4-DRI regulates endothelial cell senescence via the P53 signaling pathway.Frontiers in bioengineering and biotechnology · 2025Article
Corrections and comments
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Authors and funding
21 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The mechanisms underlying the development of glomerular lesions during aging are largely unknown. It has been suggested that senescence might play a role, but the pathophysiological link between senescence and lesion development remains unexplained. Here, we uncovered an unexpected role for glomerular endothelial cells during aging. In fact, we discovered a detrimental cross-talk between senescent endothelial cells and podocytes, through PAI-1. In vivo, selective inactivation of PAI-1 in endothelial cells protected glomeruli from lesion development and podocyte loss in aged mice. In vitro, blocking PAI-1 in supernatants from senescent endothelial cells prevented podocyte apoptosis. Consistently, depletion of senescent cells prevented podocyte loss in old p16 INK-ATTAC transgenic mice. Importantly, these experimental findings are relevant to humans. We showed that glomerular PAI-1 expression was predictive of poor outcomes in transplanted kidneys from elderly donors. In addition, we observed that in elderly patients, urinary PAI-1 was associated with age-related chronic kidney disease. Altogether, these results uncover a novel mechanism of kidney disease and identify PAI-1 as a promising biomarker of kidney dysfunction in allografts from elderly donors.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.