ArticleRedox biology2018
Iron accumulation in senescent cells is coupled with impaired ferritinophagy and inhibition of ferroptosis.
Article in Redox biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 276 papers, 1 of them a synthesis that pooled it.
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Who cites it
276 citing papers in PubMed, 1 synthesis or guideline pooled it, 423 citations in OpenAlex.
- Ferroptosis and Senescence: A Systematic Review.International journal of molecular sciences · 2023Pooled it
- Microenvironmental barriers to healing in osteoradionecrosis and opportunities for regenerative intervention.Bioactive materials · 2027Review
- The Iron Lung: Ferroptosis and Iron Regulation in Aging and Lung Diseases.Physiology (Bethesda, Md.) · 2027Review
- Ferroptosis in liver biology and diseases.Hepatology communications · 2026Review
- TFEB Attenuates Silver Nanoparticle-Induced Pulmonary Ferroptosis by Preserving Lysosomal Integrity and Limiting Iron Dysregulation.Journal of applied toxicology : JAT · 2026Article
- Cuproptosis and ferroptosis: signal pathways, diseases and therapeutic targets.Signal transduction and targeted therapy · 2026Review
- SOCS2 Downregulation Is Associated with a Ferro-Aging-Related Transcriptomic Signature in Proximal Tubular Cells in Chronic Kidney Disease.Biomedicines · 2026Article
- The SVP-FRO6 Module Integrates the Control of Leaf Senescence and Flowering in Arabidopsis.Plant, cell & environment · 2026Article
- A Microenvironment-Adaptive Scaffold Rejuvenates Peripheral Nerve Regeneration During Aging Via Dual Modulation of Ferroptotic Stimuli in Schwann Cells.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Ferroptosis-Senescence Crosstalk in Sepsis-Associated Acute Lung Injury: Mechanisms and Therapeutic Opportunities.Biomedicines · 2026Review
- Ferroptosis and aging: Inducing and catalyzing neurodegenerative diseases.Neural regeneration research · 2026Article
- Acid ceramidase modulates the lipid profile and exacerbates sensitivity to ferroptosis in WI-38 replicative senescent cells.Cell death & disease · 2026Article
- Lysosomes in Ferroptosis: Regulatory Mechanisms and Molecular Targets.Molecules (Basel, Switzerland) · 2026Review
- Microglial checkpoint collapse in Alzheimer's disease: a tri-axial framework for biomarker-informed neuroimmune therapy.Journal of neuroinflammation · 2026Review
- TMEM87a Maintains Cardiomyocyte Integrity by Limiting Ferroptosis in Dilated Cardiomyopathy.Annals of the New York Academy of Sciences · 2026Article
- Ferroptosis in musculoskeletal disorders: Emerging mechanisms and therapeutic opportunities (Review).International journal of molecular medicine · 2026Review
- Multilayer Proteome and Metabolome-Based Validation Uncovers Combined Regulatory Roles and Predictive Values of 6 RNA Modifications and Cellular Senescence in Alzheimer's Disease.CNS neuroscience & therapeutics · 2026Article
- HIF-1α attenuates ferroptosis-associated dermal fibroblast senescence via modulation of NF-κB-DPP4 signaling.Journal of translational medicine · 2026Article
- Association Between Ferroptosis and Acute Kidney Disease (AKD): Unveiling the Expression of Genes Related to Iron Regulatory Metabolism.Biochemical genetics · 2026Article
- Crosstalk between autophagy and ferroptosis in liver diseases (Review).International journal of molecular medicine · 2026Review
216 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cellular senescence is characterised by the irreversible arrest of proliferation, a pro-inflammatory secretory phenotype and evasion of programmed cell death mechanisms. We report that senescence alters cellular iron acquisition and storage and also impedes iron-mediated cell death pathways. Senescent cells, regardless of stimuli (irradiation, replicative or oncogenic), accumulate vast amounts of intracellular iron (up to 30-fold) with concomitant changes in the levels of iron homeostasis proteins. For instance, ferritin (iron storage) levels provided a robust biomarker of cellular senescence, for associated iron accumulation and for resistance to iron-induced toxicity. Cellular senescence preceded iron accumulation and was not perturbed by sustained iron chelation (deferiprone). Iron accumulation in senescent cells was driven by impaired ferritinophagy, a lysosomal process that promotes ferritin degradation and ferroptosis. Lysosomal dysfunction in senescent cells was confirmed through several markers, including the build-up of microtubule-associated protein light chain 3 (LC3-II) in autophagosomes. Impaired ferritin degradation explains the iron accumulation phenotype of senescent cells, whereby iron is effectively trapped in ferritin creating a perceived cellular deficiency. Accordingly, senescent cells were highly resistant to ferroptosis. Promoting ferritin degradation by using the autophagy activator rapamycin averted the iron accumulation phenotype of senescent cells, preventing the increase of TfR1, ferritin and intracellular iron, but failed to re-sensitize these cells to ferroptosis. Finally, the enrichment of senescent cells in mouse ageing hepatic tissue was found to accompany iron accumulation, an elevation in ferritin and mirrored our observations using cultured senescent cells.
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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.