ArticleNature aging2025
Clusterin drives myeloid bias in aged hematopoietic stem cells by regulating mitochondrial function.
Article in Nature aging, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
18 citing papers in PubMed.
- Mechanisms of Hematopoietic Stem Cell Aging and Emerging Rejuvenation Strategies.Stem cell reviews and reports · 2026Review
- Age-related IGF-1 decline permits a redox-sensitive transcriptional shift that directs hematopoiesis toward a CCR2Redox biology · 2026Article
- P-selectin delineates conserved functional heterogeneity in early hematopoietic stem cell aging in humans and mice.The EMBO journal · 2026Article
- Targeting cellular senescence alleviates bone marrow aging.bioRxiv : the preprint server for biology · 2026Article
- The ageing immune system as a driver of systemic ageing.Nature reviews. Immunology · 2026Review
- No Simple Fluke: Schistosomiasis as an Emerging Regulator of Haematopoiesis.Parasite immunology · 2026Review
- Improving lymphopoiesis in aged bone marrow.Current opinion in hematology · 2026Review
- A kinetics-based model of haematopoiesis reveals extrinsic regulation of skewed lineage output from stem cells.Nature cell biology · 2026Article
- Opposing Association of Lung Neutrophils and PD-L1Aging cell · 2026Article
- Insights into the therapeutic strategies for aging and aging-associated diseases.Signal transduction and targeted therapy · 2026Review
- Aging mechanisms and rejuvenation strategies for hematopoietic stem cells.Genome biology · 2026Review
- Immunometabolic resistors of aging in long-lived golden spiny mice.Science advances · 2026Article
- Epigenetic profiling of hematopoietic stem cells from male mice identifies KDR and PU.1 as regulators of aging transcriptome and caloric restriction response.Nature communications · 2026Article
- Immunosenescence as a driver of the transition from frailty to multimorbidity.Frontiers in immunology · 2026Review
- Decoding the tumor-aging axis: from bench to clinical.Frontiers in immunology · 2026Review
- Article
- The systemic costs of hematopoietic stem cell aging.Development (Cambridge, England) · 2025Review
- Thyroid hormones, mitochondria, aging, and cancer.Frontiers in endocrinology · 2025Review
Corrections and comments
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Authors and funding
8 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Aged hematopoietic stem cells (HSCs) exhibit diminished self-renewal and myeloid-biased differentiation with a decline in hematopoiesis and adaptive immune function. However, the molecular regulation of this impaired function remains largely unknown. Here, through an in vivo CRISPR-Cas9-based screen, we uncovered clusterin (Clu) as a driver of biased differentiation. Clu is upregulated in aged HSCs, and its knockout diminishes biased differentiation. Clu promotes mitochondrial hyperfusion by interacting with Mfn2 in aged HSCs, and its ablation attenuates oxidative phosphorylation, improves mitophagy, and reverses myeloid-biased differentiation via the OXPHOS-p38-Cebpb axis. Transplantation of Clu-depleted aged HSCs into middle-aged mice results in balanced hematopoiesis and improved physical functions. Together, our data identify Clu as a critical regulator of aging-associated myeloid bias and reveal an Mfn2-OXPHOS-p38-Cebpb axis as the mechanism underlying how Clu upregulation in aged HSCs leads to myeloid-biased differentiation, providing a target for rejuvenation of aged hematopoietic and immune systems.
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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 Socratic graph.