ArticleeLife2023
Impaired iron recycling from erythrocytes is an early hallmark of aging.
Article in eLife, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 2 of them syntheses that pooled it.
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Who cites it
27 citing papers in PubMed, 2 syntheses or guidelines pooled it, 35 citations in OpenAlex.
- Shared and niche-specific transcriptional signatures of macrophage aging revealed by a cross-tissue meta-analysis.BMC biology · 2026Pooled it
- Ferroptosis in gouty arthritis: a potential therapeutic strategy.Frontiers in immunology · 2026Pooled it
- Tissue-resident colon macrophages shape the microbiome and regulate mucosal healing via ferroportin.Cell reports · 2026Article
- Iron Compartmentalisation and Vascular Endothelial Cell Dysfunction.Antioxidants (Basel, Switzerland) · 2026Review
- SPIC-dependent erythrophagocytic macrophages drive granuloma formation and pathogen persistence during intracellular bacterial infection.bioRxiv : the preprint server for biology · 2026Article
- Red Blood Cells Internalize Extracellular DNA via Apoptotic Bodies with Clinical Relevance to Cancer Patients.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Osteocytic Lipocalin-2 regulates bone formation locally through iron-dependent ferroptosis and Wnt suppression.Cell death discovery · 2026Article
- Liver sinusoidal endothelial cells constitute a major route for hemoglobin clearance.EMBO reports · 2026Article
- Aging at the Crossroads of Cuproptosis and Ferroptosis: From Molecular Pathways to Age-Related Pathologies and Therapeutic Perspectives.International journal of molecular sciences · 2026Review
- Iron as an immunometabolic signal in infection and inflammation.Frontiers in immunology · 2026Review
- High intestinal iron absorption induced by decreased hepcidin leads to imbalance of iron metabolism in aging mice.Biogerontology · 2025Article
- Heme and iron toxicity in the aged spleen impairs T cell immunity through iron deprivation.Nature aging · 2025Article
- The SLC-ome of membrane transport: From molecular discovery to physiology and clinical applications.Physiological reviews · 2025Review
- Association of dietary intake and whole blood essential trace elements with frailty in older adults: a cross-sectional study.Aging clinical and experimental research · 2025Article
- Iron trapping in macrophages reshapes the homeostasis of the haematopoietic system.British journal of haematology · 2025Article
- 5' terminal nucleotide determines the immunogenicity of IVT RNAs.Nucleic acids research · 2025Article
- Effects of genetic ablation and pharmacological inhibition of HuR on gene expression, iron metabolism, and hormone levels.BMC biology · 2025Article
- Exercise mitigates Alzheimer's disease by targeting ferroptosis driven by cellular senescence.Frontiers in cell and developmental biology · 2025Review
- DMT1 knockout abolishes ferroptosis induced mitochondrial dysfunction in C. elegans amyloid β proteotoxicity.Free radical biology & medicine · 2024Article
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Corrections and comments
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Authors and funding
17 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Aging affects iron homeostasis, as evidenced by tissue iron loading and anemia in the elderly. Iron needs in mammals are met primarily by iron recycling from senescent red blood cells (RBCs), a task chiefly accomplished by splenic red pulp macrophages (RPMs) via erythrophagocytosis. Given that RPMs continuously process iron, their cellular functions might be susceptible to age-dependent decline, a possibility that has been unexplored to date. Here, we found that 10- to 11-month-old female mice exhibit iron loading in RPMs, largely attributable to a drop in iron exporter ferroportin, which diminishes their erythrophagocytosis capacity and lysosomal activity. Furthermore, we identified a loss of RPMs during aging, underlain by the combination of proteotoxic stress and iron-dependent cell death resembling ferroptosis. These impairments lead to the retention of senescent hemolytic RBCs in the spleen, and the formation of undegradable iron- and heme-rich extracellular protein aggregates, likely derived from ferroptotic RPMs. We further found that feeding mice an iron-reduced diet alleviates iron accumulation in RPMs, enhances their ability to clear erythrocytes, and reduces damage. Consequently, this diet ameliorates hemolysis of splenic RBCs and reduces the burden of protein aggregates, mildly increasing serum iron availability in aging mice. Taken together, we identified RPM collapse as an early hallmark of aging and demonstrated that dietary iron reduction improves iron turnover efficacy.
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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 Socratic graph.