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Cell-to-cell variability and gain of methylation at polycomb CpG islands as a hallmark of aging.

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Τίτλος: Cell-to-cell variability and gain of methylation at polycomb CpG islands as a hallmark of aging.
Συγγραφείς: Masika H; Department of Developmental Biology and Cancer Research, Institute for Medical Research Israel-Canada, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel., Ruppo S; Info-CORE Bioinformatics Unit of the I-CORE at the Hebrew University of Jerusalem, Jerusalem, Israel.; Azrieli Omics Center, Center for Computational Medicine, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel., Clark SJ; Cambridge Institute of Science, Altos Labs, Cambridge, UK.; Epigenetics Programme, The Babraham Institute, Cambridge, UK., Bonder MJ; Division of Computational Genomics and Systems Genetics, German Cancer Research Center, Heidelberg, Germany.; Genome Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany.; Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.; Oncode Institute, Utrecht, The Netherlands., von Meyenn F; Laboratory of Nutrition and Metabolic Epigenetics, Department of Health Sciences and Technology, ETH Zurich, Zurich, Switzerland.; Department of Medical and Molecular Genetics, King's College London, London, UK., Hecht M; The Lautenberg Center for Immunology and Cancer Research, Institute for Medical Research Israel-Canada, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel., Orlanski S; Department of Developmental Biology and Cancer Research, Institute for Medical Research Israel-Canada, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel., Katsman E; Department of Developmental Biology and Cancer Research, Institute for Medical Research Israel-Canada, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel., Vardi-Yaakov O; Info-CORE Bioinformatics Unit of the I-CORE at the Hebrew University of Jerusalem, Jerusalem, Israel.; Azrieli Omics Center, Center for Computational Medicine, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel.; Department of Bioinformatics, Jerusalem College of Technology, Jerusalem, Israel., Zlotogorski A; Department of Dermatology, The Faculty of Medicine, Hadassah Medical Center, The Hebrew University of Jerusalem, Jerusalem, Israel., Fachler-Sharp T; Department of Dermatology, The Faculty of Medicine, Hadassah Medical Center, The Hebrew University of Jerusalem, Jerusalem, Israel., Elgavish S; Info-CORE Bioinformatics Unit of the I-CORE at the Hebrew University of Jerusalem, Jerusalem, Israel.; Azrieli Omics Center, Center for Computational Medicine, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel., Dor Y; Department of Developmental Biology and Cancer Research, Institute for Medical Research Israel-Canada, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel.; Center for Computational Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel., Reik W; Cambridge Institute of Science, Altos Labs, Cambridge, UK.; Epigenetics Programme, The Babraham Institute, Cambridge, UK., Kaplan T; Department of Developmental Biology and Cancer Research, Institute for Medical Research Israel-Canada, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel. tommy.kaplan@mail.huji.ac.il.; Center for Computational Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel. tommy.kaplan@mail.huji.ac.il.; School of Computer Science and Engineering, The Hebrew University of Jerusalem, Jerusalem, Israel. tommy.kaplan@mail.huji.ac.il.; Barts Cancer Institute, Queen Mary University of London, London, UK. tommy.kaplan@mail.huji.ac.il.; Centre for Epigenetics, Queen Mary University of London, London, UK. tommy.kaplan@mail.huji.ac.il., Cedar H; Department of Developmental Biology and Cancer Research, Institute for Medical Research Israel-Canada, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel. cedar@mail.huji.ac.il.; Center for Computational Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel. cedar@mail.huji.ac.il.
Πηγή: Nature communications [Nat Commun] 2026 Jun 09; Vol. 17 (1). Date of Electronic Publication: 2026 Jun 09.
Τύπος έκδοσης: Journal Article
Γλώσσα: English
Στοιχεία περιοδικού: Publisher: Nature Pub. Group Country of Publication: England NLM ID: 101528555 Publication Model: Electronic Cited Medium: Internet ISSN: 2041-1723 (Electronic) Linking ISSN: 20411723 NLM ISO Abbreviation: Nat Commun Subsets: MEDLINE
Imprint Name(s): Original Publication: [London] : Nature Pub. Group
Ιατρικοί όροι (MeSH): CpG Islands*/genetics , Polycomb-Group Proteins*/genetics , Polycomb-Group Proteins*/metabolism , Aging*/genetics , Cellular Senescence*/genetics , DNA Methylation*, Cell Proliferation/genetics ; Animals ; Humans ; Mice ; Single-Cell Analysis
Περίληψη: Aging is a complex multifactorial process that affects cellular function and tissue homeostasis over time. Despite substantial research, the molecular mechanisms driving cellular aging remain poorly understood. Many studies focused on changes in DNA methylation as an indicator of aging. In particular, methylation at polycomb CpG islands was shown to be predictive of phenotypic changes associated with aging. Since many age-related pathological processes are thought to originate from single cells, we asked whether polycomb CpG island methylation occurs preferentially in a subset of cells within a population. Using single-cell whole-genome methylation data across ages and tissues, we identify polycomb CpG methylation as a hallmark of cellular aging. This revealed that aging occurs at varying rates, with faster proliferating cells showing accelerated gain of methylation. Differential gene expression analysis identified changes in immune response, translation, tumorigenesis and neurodegeneration. These results challenge traditional models of homogeneous cellular aging and suggest that aging is a highly individualized process at the single-cell level, that may be driven by programmed changes in polycomb CpG island DNA methylation.
(© 2026. The Author(s).)
Competing Interests: Competing interests: The authors declare no competing interests.
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Molecular Sequence: GEO GSE89545; GSE121436; GSE225171; GSE87196; GSE106957; GSE225172; GSE121437; GSE290999
Substance Nomenclature: 0 (Polycomb-Group Proteins)
Entry Date(s): Date Created: 20260609 Date Completed: 20260726 Latest Revision: 20260729
Update Code: 20260730
PubMed Central ID: PMC13402633
DOI: 10.1038/s41467-026-74118-5
PMID: 42265112
Βάση Δεδομένων: MEDLINE
Περιγραφή
ISSN:2041-1723
DOI:10.1038/s41467-026-74118-5