ArticleAging cell2024
A new gene signature for endothelial senescence identifies self-RNA sensing by retinoic acid-inducible gene I as a molecular facilitator of vascular aging.
Article in Aging cell, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed.
- Mechanometabolic endothelial senescence as a translational framework for cardiometabolic vascular disease and vascular ageing.Molecular biology reports · 2026Review
- Inflammaging Beyond Biomarkers: Molecular Mechanisms and Therapeutic Opportunities.Current issues in molecular biology · 2026Review
- Advanced drug delivery platforms targeting cellular senescence: A promising strategy for cancer therapy.Acta pharmaceutica Sinica. B · 2026Review
- Overview of molecular signatures of senescence and associated resources: pros and cons.FEBS open bio · 2026Review
- Senolytic Treatment With Fisetin Reverses Age-Related Endothelial Dysfunction Partially Mediated by SASP Factor CXCL12.Aging cell · 2026Article
- Mild traumatic brain injury promotes chronic cerebrovascular inflammation and glymphatic suppression.Molecular neurodegeneration advances · 2026Article
- Comparative analysis of BMP signaling in human ECFCs reveals vascular bed-dependent ALK2 expression.Vascular biology (Bristol, England) · 2026Article
- RIG-I-driven CDKN1A stabilization reinforces cellular senescence.Science China. Life sciences · 2025Article
- The Role of Endothelial Senescence in the Pathogenesis of Diabetic Retinopathy.International journal of molecular sciences · 2025Review
- Emerging insights in senescence: pathways from preclinical models to therapeutic innovations.npj aging · 2024Review
- Article
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Authors and funding
9 authors.
Funding
Abstract
The number of senescent vascular endothelial cells increases during aging and their dysfunctional phenotype contributes to age-related cardiovascular disease. Identification of senescent cells is challenging as molecular changes are often tissue specific and occur amongst clusters of normal cells. Here, we established, benchmarked, and validated a new gene signature called EndoSEN that pinpoints senescent endothelial cells. The EndoSEN signature was enriched for interferon-stimulated genes (ISG) and correlated with the senescence-associated secretory phenotype (SASP). SASP establishment is classically attributed to DNA damage and cyclic GMP-AMP synthase activation, but our results revealed a pivotal role for RNA accumulation and sensing in senescent endothelial cells. Mechanistically, we showed that endothelial cell senescence hallmarks include self-RNA accumulation, RNA sensor RIG-I upregulation, and an ISG signature. Moreover, a virtual model of RIG-I knockout in endothelial cells underscored senescence as a key pathway regulated by this sensor. We tested and confirmed that RIG-I knockdown was sufficient to extend the lifespan and decrease the SASP in endothelial cells. Taken together, our evidence suggests that targeting RNA sensing is a potential strategy to delay vascular aging.
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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.