Evidence map›Paper›PMID 39178844›Full record

ArticleStem cell reports2024

Dissecting the impact of differentiation stage, replicative history, and cell type composition on epigenetic clocks.

Rebecca Gorelov, Aaron Weiner, Aaron Huebner, Masaki Yagi, Amin Haghani, Robert Brooke, Steve Horvath, Konrad Hochedlinger

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Stem cell reports, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing 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

7 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
  4. Hallmarks of stem cell aging.Cell stem cell · 2025
    Review
  5. Article
  6. Review
  7. Article
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

8 authors.

Rebecca GorelovMassachusetts General Hospital Department of Molecular Biology, Boston, MA 02114, USA; Massachusetts General Hospital Cancer Center and Center for Regenerative Medicine, Boston, MA 02114, USA; Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02139, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
Aaron WeinerMassachusetts General Hospital Department of Molecular Biology, Boston, MA 02114, USA; Massachusetts General Hospital Cancer Center and Center for Regenerative Medicine, Boston, MA 02114, USA; Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02139, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
Aaron HuebnerMassachusetts General Hospital Department of Molecular Biology, Boston, MA 02114, USA; Massachusetts General Hospital Cancer Center and Center for Regenerative Medicine, Boston, MA 02114, USA; Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02139, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
Masaki YagiMassachusetts General Hospital Department of Molecular Biology, Boston, MA 02114, USA; Massachusetts General Hospital Cancer Center and Center for Regenerative Medicine, Boston, MA 02114, USA; Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02139, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
Amin HaghaniDepartment of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; Altos Labs, San Diego, CA 92121, USA.
Robert BrookeEpigenetic Clock Development Foundation, Torrance, CA 90502, USA.
Steve HorvathDepartment of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; Altos Labs, San Diego, CA 92121, USA; Epigenetic Clock Development Foundation, Torrance, CA 90502, USA; Department of Biostatistics, School of Public Health, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Konrad HochedlingerMassachusetts General Hospital Department of Molecular Biology, Boston, MA 02114, USA; Massachusetts General Hospital Cancer Center and Center for Regenerative Medicine, Boston, MA 02114, USA; Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02139, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA. Electronic address: khochedlinger@helix.mgh.harvard.edu.

Funding

Investigating the direct reprogramming of fibroblasts into skeletal muscle progenitorsR01AR077695 · NIAMS · MASSACHUSETTS GENERAL HOSPITAL · PI HOCHEDLINGER, KONRAD · 2020 to 2024
$2.2M
NIAMS NIH HHS R01 AR077695
6 · The paper itself

Abstract

Epigenetic clocks, built on DNA methylation patterns of bulk tissues, are powerful age predictors, but their biological basis remains incompletely understood. Here, we conducted a comparative analysis of epigenetic age in murine muscle, epithelial, and blood cell types across lifespan. Strikingly, our results show that cellular subpopulations within these tissues, including adult stem and progenitor cells as well as their differentiated progeny, exhibit different epigenetic ages. Accordingly, we experimentally demonstrate that clocks can be skewed by age-associated changes in tissue composition. Mechanistically, we provide evidence that the observed variation in epigenetic age among adult stem cells correlates with their proliferative state, and, fittingly, forced proliferation of stem cells leads to increases in epigenetic age. Collectively, our analyses elucidate the impact of cell type composition, differentiation state, and replicative potential on epigenetic age, which has implications for the interpretation of existing clocks and should inform the development of more sensitive clocks.

Indexed as

Cell DifferentiationDNA MethylationEpigenesis, GeneticAdult Stem CellsAgingAnimalsBiological ClocksCell ProliferationMiceMice, Inbred C57BLadult Stemagingcell ProliferationdifferentiationDNA methylationepigenetic clocks

Identifiers

PMID39178844
PMCPMC11411293

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

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.