Evidence map›Paper›PMID 40664208›Full record

ArticleCell reports2025

Time is encoded by methylation changes at clustered CpG sites.

Bracha-Lea Ochana, Daniel Nudelman, Daniel Cohen, Ayelet Peretz, Sheina Piyanzin, Ofer Gal Rosenberg, Amit Horn, Netanel Loyfer, Miri Varshavsky, Ron Raisch and 7 more

Abstract read
PubMed Publisher
In one paragraph

Article in Cell reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed, 1 pooled it
–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

3 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Article
  3. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

17 authors.

Bracha-Lea OchanaDepartment of Developmental Biology and Cancer Research, Institute for Medical Research Israel-Canada, The Hebrew University-Hadassah Medical School, Jerusalem, Israel.
Daniel NudelmanSchool of Computer Science and Engineering, The Hebrew University of Jerusalem, Jerusalem, Israel.
Daniel CohenDepartment of Developmental Biology and Cancer Research, Institute for Medical Research Israel-Canada, The Hebrew University-Hadassah Medical School, Jerusalem, Israel.
Ayelet PeretzDepartment of Developmental Biology and Cancer Research, Institute for Medical Research Israel-Canada, The Hebrew University-Hadassah Medical School, Jerusalem, Israel.
Sheina PiyanzinDepartment of Developmental Biology and Cancer Research, Institute for Medical Research Israel-Canada, The Hebrew University-Hadassah Medical School, Jerusalem, Israel.
Ofer Gal RosenbergDepartment of Developmental Biology and Cancer Research, Institute for Medical Research Israel-Canada, The Hebrew University-Hadassah Medical School, Jerusalem, Israel.
Amit HornDepartment of Developmental Biology and Cancer Research, Institute for Medical Research Israel-Canada, The Hebrew University-Hadassah Medical School, Jerusalem, Israel.
Netanel LoyferSchool of Computer Science and Engineering, The Hebrew University of Jerusalem, Jerusalem, Israel.
Miri VarshavskySchool of Computer Science and Engineering, The Hebrew University of Jerusalem, Jerusalem, Israel.
Ron RaischSchool of Computer Science and Engineering, The Hebrew University of Jerusalem, Jerusalem, Israel.
Ilona ShapiroBraun School of Public Health, The Hebrew University of Jerusalem, Jerusalem, Israel.
Yechiel FriedlanderBraun School of Public Health, The Hebrew University of Jerusalem, Jerusalem, Israel.
Hagit HochnerBraun School of Public Health, The Hebrew University of Jerusalem, Jerusalem, Israel.
Benjamin GlaserDepartment of Endocrinology and Metabolism, Hadassah Medical Center and Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel.
Yuval DorDepartment of Developmental Biology and Cancer Research, Institute for Medical Research Israel-Canada, The Hebrew University-Hadassah Medical School, Jerusalem, Israel. Electronic address: yuvald@ekmd.huji.ac.il.
Tommy KaplanDepartment of Developmental Biology and Cancer Research, Institute for Medical Research Israel-Canada, The Hebrew University-Hadassah Medical School, Jerusalem, Israel; School of Computer Science and Engineering, The Hebrew University of Jerusalem, Jerusalem, Israel. Electronic address: tommy@cs.huji.ac.il.
Ruth ShemerDepartment of Developmental Biology and Cancer Research, Institute for Medical Research Israel-Canada, The Hebrew University-Hadassah Medical School, Jerusalem, Israel. Electronic address: shemer.ru@mail.huji.ac.il.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Age-dependent changes in DNA methylation allow chronological and biological age inference, but the underlying mechanisms remain unclear. Using ultra-deep sequencing of >300 blood samples from healthy individuals, we show that age-dependent methylation changes occur regionally across clusters of CpG sites either stochastically or in a coordinated block-like manner. Deep learning of single-molecule patterns from two genomic loci predicts chronological age with a median accuracy of 1.36-1.7 years on held-out samples, dramatically improving current clocks. Predictions are robust to sex, smoking, BMI, and biological age measures. Longitudinal 10-year analysis shows that early deviations from predicted age persist throughout life, and subsequent changes faithfully record time. Strikingly, accurate chronological age predictions are possible using as few as 50 DNA molecules, suggesting that age is encoded by individual cells. Overall, DNA methylation changes in clustered CpG sites illuminate the principles of time measurement by cells and tissues and facilitate medical and forensic applications.

Indexed as

AgingCpG IslandsDNA MethylationAdultAgedFemaleHumansMaleMiddle AgedYoung Adultage predictionagingbiological agechronological agecomputational biologyCP: MetabolismCP: Molecular biologydeep learningDNA methylationepigeneticsforensicsneural networks

Identifiers

What OpenQuestion holds

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Registered trials

None linked

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.