ArticleAging cell2018
Oxidation resistance 1 is a novel senolytic target.
Article in Aging cell, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers.
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Who cites it
72 citing papers in PubMed, 123 citations in OpenAlex.
- Molecular hydrogen: a potential guardian against environmental radiation damage.Medical gas research · 2027Review
- Topological Quantum Biomaterials Enable Pyroptosis-Senescence Coupling for Enhanced Colorectal Cancer Therapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Insights into the therapeutic strategies for aging and aging-associated diseases.Signal transduction and targeted therapy · 2026Review
- The effects of the "living high-training low" model on key proteins involved in cellular aerobic and anaerobic metabolism in male C57BL/6J mice.Physiological reports · 2026Article
- Identification of prognostic genes associated with mitochondria and macrophage polarization in prostate adenocarcinoma based on transcriptome and Mendelian randomization analysis.Discover oncology · 2025Article
- Senolytics as Modulators of Critical Signaling Pathways: a Promising Strategy to Combat Brain Aging and Neurodegenerative Disorders.Molecular neurobiology · 2025Review
- Targeting DNA damage in ageing: towards supercharging DNA repair.Nature reviews. Drug discovery · 2025Review
- Anti-senescence therapies: a new concept to address cardiovascular disease.Cardiovascular research · 2025Review
- New Insights into the Role of Cellular Senescence and Its Therapeutic Implications in Ocular Diseases.Bioengineering (Basel, Switzerland) · 2025Review
- The Potential of Polyphenols in Modulating the Cellular Senescence Process: Implications and Mechanism of Action.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Cellular senescence as a key contributor to secondary neurodegeneration in traumatic brain injury and stroke.Translational neurodegeneration · 2024Review
- Drug delivery for age-related bone diseases: From therapeutic targets to common and emerging therapeutic strategies.Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2024Review
- Decoding senescence of aging single cells at the nexus of biomaterials, microfluidics, and spatial omics.npj aging · 2024Review
- The Quest for Eternal Youth: Hallmarks of Aging and Rejuvenating Therapeutic Strategies.Biomedicines · 2024Review
- Therapeutic targeting of senescent cells in the CNS.Nature reviews. Drug discovery · 2024Review
- Cellular senescence and SASP in tumor progression and therapeutic opportunities.Molecular cancer · 2024Review
- Therapy-induced senescence through the redox lens.Redox biology · 2024Review
- Characterisation of premature cell senescence in Alzheimer's disease using single nuclear transcriptomics.Acta neuropathologica · 2024Article
- Revolutionizing Diabetic Foot Ulcer Care: The Senotherapeutic Approach.Aging and disease · 2024Review
- Computational identification of natural senotherapeutic compounds that mimic dasatinib based on gene expression data.Scientific reports · 2024Article
12 more citing papers are in PubMed but not listed here.
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Authors and funding
15 authors at 5 institutions in 2 countries.
Funding
Abstract
The selective depletion of senescent cells (SCs) by small molecules, termed senolytic agents, is a promising therapeutic approach for treating age-related diseases and chemotherapy- and radiotherapy-induced side effects. Piperlongumine (PL) was recently identified as a novel senolytic agent. However, its mechanism of action and molecular targets in SCs was unknown and thus was investigated. Specifically, we used a PL-based chemical probe to pull-down PL-binding proteins from live cells and then mass spectrometry-based proteomic analysis to identify potential molecular targets of PL in SCs. One prominent target was oxidation resistance 1 (OXR1), an important antioxidant protein that regulates the expression of a variety of antioxidant enzymes. We found that OXR1 was upregulated in senescent human WI38 fibroblasts. PL bound to OXR1 directly and induced its degradation through the ubiquitin-proteasome system in an SC-specific manner. The knockdown of OXR1 expression by RNA interference significantly increased the production of reactive oxygen species in SCs in conjunction with the downregulation of antioxidant enzymes such as heme oxygenase 1, glutathione peroxidase 2, and catalase, but these effects were much less significant when OXR1 was knocked down in non-SCs. More importantly, knocking down OXR1 selectively induced apoptosis in SCs and sensitized the cells to oxidative stress caused by hydrogen peroxide. These findings provide new insights into the mechanism by which SCs are highly resistant to oxidative stress and suggest that OXR1 is a novel senolytic target that can be further exploited for the development of new senolytic agents.
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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.