ArticleAging cell2024
Rutin is a potent senomorphic agent to target senescent cells and can improve chemotherapeutic efficacy.
Article in Aging cell, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 67 papers.
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Who cites it
67 citing papers in PubMed, 110 citations in OpenAlex.
- Immunotherapy and senolytics in head and neck squamous cell carcinoma: phase 2 trial results.Nature medicine · 2025Trial
- Cellular senescence and regulated cell death in cancer: mechanisms, cross-regulatory networks and therapeutic implications.Journal of hematology & oncology · 2026Review
- HPRT1 drives mitochondrial metabolic reprogramming and immunosuppressive microenvironment in oral squamous cell carcinoma.Apoptosis : an international journal on programmed cell death · 2026Article
- Drought Stress Mediated Changes in Food Crops: Mechanisms and Remediation Strategies.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Skin Aging: From Molecular Mechanisms to Therapeutic and Technological Innovations.Journal of cellular and molecular medicine · 2026Review
- Plant-Derived Senotherapeutics in Cellular Senescence: A Scoping Review of Preclinical Evidence, Mechanistic Pathways, and Metabolomic-Guided Discovery.International journal of molecular sciences · 2026Article
- SIRT1 in brain aging: molecular mechanisms and therapeutic potential of pharmacological and natural modulators.Biogerontology · 2026Review
- Cellular Senescence and Aging: Mechanisms, Disease Convergence, and Therapeutic Frontiers.MedComm · 2026Review
- Combined metformin and Taurine attenuate age-related bone loss.Molecular biology reports · 2026Article
- Immunosenescence in systemic and multi-organ aging: mechanisms, inter-organ crosstalk, and translational opportunities.npj aging · 2026Review
- Research Progress and Prospects of Flavonoids in the Treatment of Diseases by Regulating Autophagy: A Narrative Review.Molecules (Basel, Switzerland) · 2026Review
- Methyl Caffeate Binds to IQGAP1 and Inhibits the Senescence-Associated Secretory Phenotype in Senescent Cells.International journal of molecular sciences · 2026Article
- Olive Leaf Extract Health-Promoting and Anti-Tumor Properties: An Adjunct Therapy in Pediatric Oncology?Nutrients · 2026Review
- Dual Roles and Therapeutic Prospects of Proximal Tubular Epithelial Cell Senescence in Acute Kidney Injury.Biomolecules · 2026Review
- Rutin as a Potential Therapeutic Agent for Multi-Organ Ischemia-Reperfusion Injury: From Multidimensional Mechanisms to Clinical Translation.Molecules (Basel, Switzerland) · 2026Review
- The natural flavonoid dihydromyricetin targets senescent cells via PRDX2 and alleviates age-related diseases.Nature communications · 2026Article
- Targeting age-related LINE-1 activation alleviates cardiac aging.Nature aging · 2026Article
- PI3K/AKT signaling pathway: new strategies for treating atherosclerosis with plant-derived compounds.Frontiers in pharmacology · 2026Review
- Natural Products as Anti-Senescence-Associated Secretory Phenotype (SASP) Agents.Current medicinal chemistry · 2026Review
- Article
7 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
- Erratum issued
Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
Abstract
Aging is a major risk factor for most chronic disorders, for which cellular senescence is one of the central hallmarks. Senescent cells develop the pro-inflammatory senescence-associated secretory phenotype (SASP), which significantly contributes to organismal aging and age-related disorders. Development of senotherapeutics, an emerging class of therapeutic agents to target senescent cells, allows to effectively delay aging and alleviate chronic pathologies. Here we report preliminary outputs from screening of a natural medicinal agent (NMA) library for senotherapeutic candidates and validated several agents with prominent potential as senomorphics. Rutin, a phytochemical constituent found in a number of plants, showed remarkable capacity in targeting senescent cells by dampening expression of the full spectrum SASP. Further analysis indicated that rutin restrains the acute stress-associated phenotype (ASAP) by specifically interfering with the interactions of ATM with HIF1α, a master regulator of cellular and systemic homeostasis activated during senescence, and of ATM with TRAF6, part of a key signaling axis supporting the ASAP development toward the SASP. Conditioned media produced by senescent stromal cells enhanced the malignant phenotypes of prostate cancer cells, including in vitro proliferation, migration, invasion, and more importantly, chemoresistance, while rutin remarkably downregulated these gain-of-functions. Although classic chemotherapy reduced tumor progression, the treatment outcome was substantially improved upon combination of a chemotherapeutic agent with rutin. Our study provides a proof of concept for rutin as an emerging natural senomorphic agent, and presents an effective therapeutic avenue for alleviating age-related pathologies including cancer.
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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.