ArticleNature aging2022
Destabilizing heterochromatin by APOE mediates senescence.
Article in Nature aging, 2022. 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 61 papers, 2 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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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
61 citing papers in PubMed, 2 syntheses or guidelines pooled it, 95 citations in OpenAlex.
- Rejuvenation of Bone Marrow Mesenchymal Stem Cells: Mechanisms and Their Application in Senile Osteoporosis Treatment.Biomolecules · 2025Pooled it
- A bibliometric and visual analysis of the impact of senescence on tumor immunotherapy.Frontiers in immunology · 2025Pooled it
- Piezo1-mediated mechanotransduction in bone formation and fracture repair.Biochemistry and biophysics reports · 2026Review
- Genomic, epigenomic and transcriptomic regulation of cellular senescence.Nature reviews. Genetics · 2026Review
- Microglia activation by derepression of endogenous retroviruses drives inflammation and cellular senescence.Nature neuroscience · 2026Article
- Review
- Exceptional Longevity Modifying Allele APOE2 Promotes DNA Signaling Pathways Resisting Cellular Senescence in Human Neurons.Aging cell · 2026Article
- CRISPR Applications in Alzheimer's Disease: From High-Throughput Genetic Screening to Precision Editing and CNS Delivery.International journal of molecular sciences · 2026Review
- Integrated epigenetic networks in aging: from histone to RNA modifications.Journal of translational medicine · 2026Review
- Apolipoprotein E Deficiency Impairs Human Microglial Proliferation Accompanied by Elevated Cellular Oxidative Stress.Journal of cellular and molecular medicine · 2026Article
- Mechanosensor YAP orchestrates human neural rosette morphogenesis via TEAD4-LEF1 transcriptional nexus.Science China. Life sciences · 2026Article
- Interconnected Pathways and Therapeutic Implications for Cardiovascular Aging and Diseases.JACC. Asia · 2026Review
- Endothelial epigenetic senescence driven microglial activation mediates cardio-retinal neuroinflammation in heart failure.Theranostics · 2026Article
- Mesenchymal stromal cells in age-related neurodegenerative disorders: mechanisms, translational barriers, and precision strategies.Frontiers in immunology · 2026Review
- High-order chromatin structures mediated by phase separation in cell senescence.Frontiers in molecular biosciences · 2026Review
- The drug discovery and therapeutic nano-strategies targeting cellular senescence.Materials today. Bio · 2025Review
- Biomarkers of ageing of humans and non-human primates.Nature reviews. Molecular cell biology · 2025Review
- Proteomic landscape of multidimensional aging phenotypes.Genome medicine · 2025Article
- Thymosin beta 4 as an Alzheimer disease intervention target identified using human brain organoids.Stem cell reports · 2025Article
- Single-cell profiling identifies hair cell SLC35F1 deficiency as a signature of primate cochlear aging.Nature aging · 2025Article
1 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
- Erratum issued
- Erratum issued
Authors and funding
20 authors at 6 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Apolipoprotein E (APOE) is a component of lipoprotein particles that function in the homeostasis of cholesterol and other lipids. Although APOE is genetically associated with human longevity and Alzheimer's disease, its mechanistic role in aging is largely unknown. Here, we used human genetic, stress-induced and physiological cellular aging models to explore APOE-driven processes in stem cell homeostasis and aging. We report that in aged human mesenchymal progenitor cells (MPCs), APOE accumulation is a driver for cellular senescence. By contrast, CRISPR-Cas9-mediated deletion of APOE endows human MPCs with resistance to cellular senescence. Mechanistically, we discovered that APOE functions as a destabilizer for heterochromatin. Specifically, increased APOE leads to the degradation of nuclear lamina proteins and a heterochromatin-associated protein KRAB-associated protein 1 via the autophagy-lysosomal pathway, thereby disrupting heterochromatin and causing senescence. Altogether, our findings uncover a role of APOE as an epigenetic mediator of senescence and provide potential targets to ameliorate aging-related diseases.
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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.