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

Autor: Eisenberg DTA; Department of Anthropology, University of Washington, Seattle, WA, USA. dtae@uw.edu.; Center for Studies in Demography and Ecology, University of Washington, Seattle, WA, USA. dtae@uw.edu., Ryan CP; Columbia Aging Center GeroScience Computational Core, Mailman School of Public Health, Columbia University, New York, NY, 10032, USA., Lee NR; USC-Office of Population Studies Foundation, Inc., University of San Carlos, Cebu City, Philippines., Carba DB; USC-Office of Population Studies Foundation, Inc., University of San Carlos, Cebu City, Philippines., MacIsaac JL; Edwin S.H. Leong Healthy Aging Program, Department of Medical Genetics, University of British Columbia, Vancouver, Canada., Dever K; Edwin S.H. Leong Healthy Aging Program, Department of Medical Genetics, University of British Columbia, Vancouver, Canada., Atashzay P; Edwin S.H. Leong Healthy Aging Program, Department of Medical Genetics, University of British Columbia, Vancouver, Canada., Kobor MS; Edwin S.H. Leong Healthy Aging Program, Department of Medical Genetics, University of British Columbia, Vancouver, Canada., Kuzawa C; Department of Anthropology, Northwestern University; Institute for Policy Research, Northwestern University, Evanston, IL, USA.
Jazyk: angličtina
Zdroj: GeroScience [Geroscience] 2024 Aug; Vol. 46 (4), pp. 3957-3969. Date of Electronic Publication: 2024 Mar 11.
DOI: 10.1007/s11357-024-01114-2
Abstrakt: 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.
(© 2024. The Author(s), under exclusive licence to American Aging Association.)
Databáze: MEDLINE
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