Evidence mapPaperPMID 42265112Full record

ArticleNature communications2026

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

Hagit Masika, Shmuel Ruppo, Stephen J Clark, Marc Jan Bonder, Ferdinand von Meyenn, Merav Hecht, Shari Orlanski, Efrat Katsman, Oriya Vardi-Yaakov, Abraham Zlotogorski and 6 more

Abstract read
In one paragraph

Article in Nature communications, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

16 authors.

Hagit MasikaDepartment of Developmental Biology and Cancer Research, Institute for Medical Research Israel-Canada, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel.
Shmuel RuppoInfo-CORE Bioinformatics Unit of the I-CORE at the Hebrew University of Jerusalem, Jerusalem, Israel.ORCID 0000-0001-9405-0049
Stephen J ClarkCambridge Institute of Science, Altos Labs, Cambridge, UK.ORCID 0000-0002-6183-491X
Marc Jan BonderDivision of Computational Genomics and Systems Genetics, German Cancer Research Center, Heidelberg, Germany.ORCID 0000-0002-8431-3180
Ferdinand von MeyennLaboratory of Nutrition and Metabolic Epigenetics, Department of Health Sciences and Technology, ETH Zurich, Zurich, Switzerland.ORCID 0000-0001-9920-3075
Merav HechtThe Lautenberg Center for Immunology and Cancer Research, Institute for Medical Research Israel-Canada, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel.
Shari OrlanskiDepartment of Developmental Biology and Cancer Research, Institute for Medical Research Israel-Canada, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel.
Efrat KatsmanDepartment of Developmental Biology and Cancer Research, Institute for Medical Research Israel-Canada, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel.ORCID 0000-0002-4897-8783
Oriya Vardi-YaakovInfo-CORE Bioinformatics Unit of the I-CORE at the Hebrew University of Jerusalem, Jerusalem, Israel.
Abraham ZlotogorskiDepartment of Dermatology, The Faculty of Medicine, Hadassah Medical Center, The Hebrew University of Jerusalem, Jerusalem, Israel.
Tahel Fachler-SharpDepartment of Dermatology, The Faculty of Medicine, Hadassah Medical Center, The Hebrew University of Jerusalem, Jerusalem, Israel.
Sharona ElgavishInfo-CORE Bioinformatics Unit of the I-CORE at the Hebrew University of Jerusalem, Jerusalem, Israel.
Yuval DorDepartment of Developmental Biology and Cancer Research, Institute for Medical Research Israel-Canada, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel.ORCID 0000-0003-2456-2289
Wolf ReikCambridge Institute of Science, Altos Labs, Cambridge, UK.ORCID 0000-0003-0216-9881
Tommy KaplanDepartment 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.ORCID 0000-0002-1892-5461
Howard CedarDepartment 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.ORCID 0000-0001-6472-9640

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

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.

Indexed as

AgingCellular SenescenceCpG IslandsDNA MethylationPolycomb-Group ProteinsAnimalsCell ProliferationHumansMiceSingle-Cell AnalysisPolycomb-Group Proteins

Identifiers

PMID42265112
PMCPMC13402633

What Socratic holds

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Registered trials

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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.