Evidence map›Paper›PMID 42230995›Full record

ArticleNature aging2026

DREAM repressive activity links somatic mutation, lifespan and disease.

Zane Koch, Shuvro P Nandi, Kate Licon, Arturo Bujarrabal-Dueso, David H Meyer, Safa Saeed, Pirunthan Perampalam, Frederick A Dick, Björn Schumacher, Ludmil B Alexandrov and 1 more

Erratum issuedAbstract read
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In one paragraph

Article in Nature aging, 2026. 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 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors.

Zane KochProgram in Bioinformatics and Systems Biology, University of California, San Diego, La Jolla, CA, USA.ORCID http://orcid.org/0000-0003-2259-3065
Shuvro P NandiDepartment of Bioengineering, University of California, San Diego, La Jolla, CA, USA.ORCID http://orcid.org/0000-0003-4855-4697
Kate LiconDepartment of Medicine, University of California, San Diego, La Jolla, CA, USA.
Arturo Bujarrabal-DuesoInstitute for Genome Stability in Aging and Disease, Medical Faculty, University and University Hospital of Cologne, Cologne, Germany.
David H MeyerInstitute for Genome Stability in Aging and Disease, Medical Faculty, University and University Hospital of Cologne, Cologne, Germany.ORCID http://orcid.org/0000-0002-5667-4720
Safa SaeedDepartment of Bioengineering, University of California, San Diego, La Jolla, CA, USA.ORCID http://orcid.org/0000-0002-8166-572X
Pirunthan PerampalamDepartment of Pathology and Laboratory Medicine, Verspeeten Family Cancer Centre, Children's Health Research Institute, Western University, London, Ontario, Canada.
Frederick A DickDepartment of Pathology and Laboratory Medicine, Verspeeten Family Cancer Centre, Children's Health Research Institute, Western University, London, Ontario, Canada.ORCID http://orcid.org/0000-0002-0047-9985
Björn SchumacherInstitute for Genome Stability in Aging and Disease, Medical Faculty, University and University Hospital of Cologne, Cologne, Germany.ORCID http://orcid.org/0000-0001-6097-5238
Ludmil B AlexandrovProgram in Bioinformatics and Systems Biology, University of California, San Diego, La Jolla, CA, USA.ORCID http://orcid.org/0000-0003-3596-4515
Trey IdekerProgram in Bioinformatics and Systems Biology, University of California, San Diego, La Jolla, CA, USA. tideker@health.ucsd.edu.ORCID http://orcid.org/0000-0002-1708-8454

Funding

TR&D 3 - Network Guided Machine LearningP41GM103504 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI IDEKER, TREY · 2012 to 2024
$17.3M
The Cancer Cell Map Initiative v2.0U54CA274502 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Emma Lundberg · 2022 to 2026
$14.2M
Illumina NovaSeq 6000 Sequencing SystemS10OD026929 · OD · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI JEPSEN, KRISTEN LYNN · 2019 to 2019
$600k
NCI NIH HHS U54 CA274502NIGMS NIH HHS P41 GM103504NIH HHS S10 OD026929
6 · The paper itself

Abstract

The DREAM complex has emerged as a central repressor of DNA repair, raising questions as to whether such repression exerts long-term effects on human health. Here we establish that DREAM-associated activity significantly impacts lifetime somatic mutation burden, and that such effects are linked to altered lifespan and age-related disease pathology. First, joint profiling of DREAM-associated activity (quantified from the expression of genes transcriptionally repressed by DREAM) and somatic mutations across a single-cell atlas of 21 mouse tissues shows that cellular niches with lower DREAM-associated activity have decreased mutation rates. Second, DREAM-associated activity predicts the varied lifespans observed across 92 mammals, with low activity marking longer-lived species. Third, reduced DREAM-associated activity in individuals with Alzheimer's disease predicts late disease onset and decreased risk for severe neuropathology. Finally, DREAM knockout in mice protects against mutation accumulation, reducing single-base substitutions by 4.2% and insertion/deletions by 19.6% in the brain. These findings position DREAM as a key regulator of aging.

Indexed as

AgingAlzheimer DiseaseDreamsLongevityMutationAnimalsBrainHumansMiceMice, Knockout

Identifiers

PMID42230995
PMCPMC13367291

What OpenQuestion holds

Textmetadata
LicenceTDM
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.