Evidence map›Paper›PMID 38466455›Full record

ArticleGeroScience2024

DNA methylation-based estimators of telomere length show low correspondence with paternal age at conception and other measures of external validity of telomere length.

Dan T A Eisenberg, Calen P Ryan, Nanette R Lee, Delia B Carba, Julie L MacIsaac, Kristy Dever, Parmida Atashzay, Michael S Kobor, Christopher Kuzawa

Abstract read
In one paragraph

Article in GeroScience, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. 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

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

9 authors.

Dan T A EisenbergDepartment of Anthropology, University of Washington, Seattle, WA, USA. dtae@uw.edu.ORCID 0000-0003-0812-1862
Calen P RyanColumbia Aging Center GeroScience Computational Core, Mailman School of Public Health, Columbia University, New York, NY, 10032, USA.ORCID 0000-0002-0550-7949
Nanette R LeeUSC-Office of Population Studies Foundation, Inc., University of San Carlos, Cebu City, Philippines.
Delia B CarbaUSC-Office of Population Studies Foundation, Inc., University of San Carlos, Cebu City, Philippines.
Julie L MacIsaacEdwin S.H. Leong Healthy Aging Program, Department of Medical Genetics, University of British Columbia, Vancouver, Canada.
Kristy DeverEdwin S.H. Leong Healthy Aging Program, Department of Medical Genetics, University of British Columbia, Vancouver, Canada.
Parmida AtashzayEdwin S.H. Leong Healthy Aging Program, Department of Medical Genetics, University of British Columbia, Vancouver, Canada.
Michael S KoborEdwin S.H. Leong Healthy Aging Program, Department of Medical Genetics, University of British Columbia, Vancouver, Canada.
Christopher KuzawaDepartment of Anthropology, Northwestern University; Institute for Policy Research, Northwestern University, Evanston, IL, USA.

Funding

UNC-CH CENTER FOR ENVIRONMENTAL HEALTH &SUSCEPTIBILITYP30ES010126 · NIEHS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Hazel B Nichols · 2001 to 2026
$36.3M
UNIV OF NORTH CAROLINA CLINICAL NUTRITION RESEARCH UNITP30DK056350 · NIDDK · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Venkata Saroja Voruganti · 1999 to 2026
$31.6M
Scientific/Technical CoreP2CHD042828 · NICHD · UNIVERSITY OF WASHINGTON · PI SARA R. CURRAN · 2017 to 2026
$6.3M
Lifecourse determinants and outcomes of epigenetic age acceleration across two generationsR01AG061006 · NIA · NORTHWESTERN UNIVERSITY · PI KUZAWA, CHRISTOPHER · 2019 to 2023
$2.6M
Genetic Epidemiology of Body Mass Index, Adiposity and Weight GainR01DK078150 · NIDDK · UNIV OF NORTH CAROLINA CHAPEL HILL · PI MOHLKE, KAREN L. · 2007 to 2010
$2.3M
An Interdisciplinary Strategy for Obesity (RMI)P20RR020649 · NCRR · UNIV OF NORTH CAROLINA CHAPEL HILL · PI POPKIN, BARRY M · 2004 to 2006
$1.7M
Effect of Health on Education &Work in Filipino YouthR01TW005596 · FIC · UNIVERSITY OF NORTH CAROLINA CHAPEL HILL · PI ADAIR, LINDA S · 2001 to 2005
$1.5M
FIC NIH HHS R01 TW005596National Science Foundation BCS- 0962282National Science Foundation BCS-1519110NCRR NIH HHS P20 RR020649NIA NIH HHS R01 AG061006NICHD NIH HHS P2C HD042828NIDDK NIH HHS P30 DK056350NIDDK NIH HHS R01 DK078150NIEHS NIH HHS P30 ES010126Office of Extramural Research, National Institutes of Health DK056350Office of Extramural Research, National Institutes of Health DK078150Office of Extramural Research, National Institutes of Health ES10126Office of Extramural Research, National Institutes of Health R01AG061006Office of Extramural Research, National Institutes of Health RR20649Office of Extramural Research, National Institutes of Health TW05596Wenner-Gren Foundation 8111
6 · The paper itself

Abstract

In humans, DNA methylation (DNAm) based estimators of telomere length (TL) have been shown to better predict TL-associated variables (e.g., age, sex, and mortality) than TL itself. The biological significance of DNAm-based estimators of TL (DNAmTL) is unclear. In vitro DNAmTL shortens with cell replications, even when telomerase is maintaining TL. Telomerase is typically suppressed in humans, except in testes. Accordingly, sperm TL increases with age, and offspring with greater paternal age at conception (PAC) have longer TL. Thus, we expect that PAC associations with DNAmTL can shed light on whether in vivo cell replications in the presence of high telomerase activity (production of sperm) shorten DNAmTL or if PAC-lengthened TL causes lengthened DNAmTL. In a pre-registered analysis, using data from 1733 blood samples from the Philippines, we examined the association between paternal age at conception (PAC) and offspring DNAmTL. We did not find an association between PAC and DNAmTL but found a positive association of paternal grandfather's age at father's conception predicting grandchild's DNAmTL. In post hoc analyses, we examined how DNAmTL versus qPCR-measured TL (qPCR-TL) correlated with measures typically associated with TL. Contrary to previous findings, on almost all measures of external validity (correlations with parental TLs, southern blot TL, and age), qPCR-TL outperformed DNAmTL. The "kilobase" units of DNAm-based estimators of TL showed considerable deviations from southern blot-derived kilobase measures. Our findings suggest that DNAmTL is not a reliable index of inherited aspects of TL and underscores uncertainty about the biological meaning of DNAmTL.

Indexed as

DNA MethylationPaternal AgeTelomereAdultAgedFemaleFertilizationHumansMaleMiddle AgedTelomere HomeostasisBioinformatic techniquesDNA methylationEpigenetic clocksTelomere length

Identifiers

PMID38466455
PMCPMC11226585

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.