Evidence map›Paper›PMID 39604704›Full record

ArticleNature aging2025

Transposable element 5mC methylation state of blood cells predicts age and disease.

Francesco Morandini, Jinlong Y Lu, Cheyenne Rechsteiner, Aladdin H Shadyab, Ramon Casanova, Beverly M Snively, Andrei Seluanov, Vera Gorbunova

Abstract read
In one paragraph

Article in Nature aging, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing 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

17 citing papers in PubMed.

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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.

Francesco MorandiniDepartment of Biology, University of Rochester, Rochester, NY, USA.ORCID http://orcid.org/0000-0003-1040-8539
Jinlong Y Lu *Department of Biology, University of Rochester, Rochester, NY, USA.ORCID http://orcid.org/0000-0003-3170-5655
Cheyenne Rechsteiner *Department of Biology, University of Rochester, Rochester, NY, USA.ORCID http://orcid.org/0000-0003-1527-2319
Aladdin H ShadyabHerbert Wertheim School of Public Health and Human Longevity Science and Division of Geriatrics, Gerontology, and Palliative Care, Department of Medicine, University of California San Diego, La Jolla, CA, USA.
Ramon CasanovaDivision of Public Health Sciences, Department of Biostatistics and Data Science, Wake Forest University School of Medicine, Winston-Salem, NC, USA.
Beverly M SnivelyDivision of Public Health Sciences, Department of Biostatistics and Data Science, Wake Forest University School of Medicine, Winston-Salem, NC, USA.
Andrei SeluanovDepartment of Biology, University of Rochester, Rochester, NY, USA. andrei.seluanov@rochester.edu.ORCID http://orcid.org/0000-0003-3400-538X
Vera GorbunovaDepartment of Biology, University of Rochester, Rochester, NY, USA. vera.gorbunova@rochester.edu.ORCID http://orcid.org/0000-0001-8979-0333

Funding

The role of hyaluronan in longevity and cancer resistance of longest-lived rodentP01AG047200 · NIA · UNIVERSITY OF ROCHESTER · PI Vadim N. Gladyshev · 2014 to 2026
$36.9M
Somatic Activation of Retrotransposition: A New Molecular Mechanism of Aging?P01AG051449 · NIA · BROWN UNIVERSITY · PI John M Sedivy · 2016 to 2026
$30.4M
The role of SIRT6 posttranslational modifications in aging and genome stability. Supplement: Testing SIRT6 activators as potential Alzheimer's disease therapy.R01AG027237 · NIA · UNIVERSITY OF ROCHESTER · PI Vera Gorbunova · 2006 to 2026
$6.2M
Regulation of epigenome stability by SIRT6 during aging. Supplement: Does centenarian variant of SIRT6 or bowhead whale SIRT6 confer protection from Alzheimer's disease?R37AG046320 · NIA · UNIVERSITY OF ROCHESTER · PI Andrei Seluanov · 2019 to 2026
$4.7M
Epigenetic Aging Biomarkers of Mild Cognitive Impairment, Alzheimer's Disease and Related Dementias, and Brain AgingRF1AG074345 · NIA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI SHADYAB, ALADDIN · 2021 to 2021
$2.1M
Regulation of genome stability by SITR6R01AG046320 · NIA · UNIVERSITY OF ROCHESTER · PI SELUANOV, ANDREI · 2014 to 2018
$1.9M
Epigenetic Aging Biomarkers of Mild Cognitive Impairment, Alzheimer's Disease and Related Dementias, and Brain AgingR01AG074345 · NIA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI SHADYAB, ALADDIN · 2024 to 2025
$1.1M
NIA NIH HHS P01 AG047200NIA NIH HHS P01 AG051449NIA NIH HHS R01 AG027237NIA NIH HHS R01 AG046320NIA NIH HHS R01 AG074345NIA NIH HHS R37 AG046320NIA NIH HHS RF1 AG074345U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging) AG027237U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging) AG047200U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging) AG051449
6 · The paper itself

Abstract

Transposable elements (TEs) are DNA sequences that expand selfishly in the genome, possibly causing severe cellular damage. While normally silenced, TEs have been shown to activate during aging. DNA 5-methylcytosine (5mC) is one of the main epigenetic modifications by which TEs are silenced and has been used to train highly accurate age predictors. Yet, one common criticism of such predictors is that they lack interpretability. In this study, we investigate the changes in TE 5mC methylation that occur during aging in human blood using published methylation array data. We find that evolutionarily young long interspersed nuclear elements 1 (L1s), the only known TEs capable of autonomous transposition in humans, undergo the fastest loss of 5mC methylation, suggesting an active mechanism of de-repression. The same young L1s also showed preferential gain in chromatin accessibility but not expression. The long terminal repeat retrotransposons THE1A and THE1C also showed very rapid 5mC loss. We then show that accurate age predictors can be trained on both 5mC methylation of individual TE copies and average methylation of TE families genome wide. Lastly, we show that while old L1s gradually lose 5mC during the entire lifespan, demethylation of young L1s only happens late in life and is associated with cancer.

Indexed as

5-MethylcytosineAgingBlood CellsDNA MethylationDNA Transposable ElementsAdultAgedEpigenesis, GeneticFemaleHumansLong Interspersed Nucleotide ElementsMaleMiddle AgedNeoplasms5-MethylcytosineDNA Transposable Elements

Identifiers

PMID39604704
PMCPMC11839465

What OpenQuestion 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 OpenQuestion graph.