Research Paper Volume 16, Issue 13 pp 10724—10748
Co-analysis of methylation platforms for signatures of biological aging in the domestic dog reveals previously unexplored confounding factors
- 1 Cancer Genetics and Comparative Genomics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA
- 2 Department of Chemistry and Biochemistry, University of California Los Angeles, Los Angeles, CA 90095, USA
- 3 Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA
- 4 Altos Labs Inc, Cambridge, United Kingdom
- 5 Department of Molecular, Cell and Developmental Biology, University of Los Angeles, Los Angeles, CA 90095, USA
Received: December 21, 2023 Accepted: May 29, 2024 Published: July 9, 2024
https://doi.org/10.18632/aging.206012How to Cite
Copyright: © 2024 Armero et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Chronological age reveals the number of years an individual has lived since birth. By contrast, biological age varies between individuals of the same chronological age at a rate reflective of physiological decline. Differing rates of physiological decline are related to longevity and result from genetics, environment, behavior, and disease. The creation of methylation biological age predictors is a long-standing challenge in aging research due to the lack of individual pre-mortem longevity data. The consistent differences in longevity between domestic dog breeds enable the construction of biological age estimators which can, in turn, be contrasted with methylation measurements to elucidate mechanisms of biological aging. We draw on three flagship methylation studies using distinct measurement platforms and tissues to assess the feasibility of creating biological age methylation clocks in the dog. We expand epigenetic clock building strategies to accommodate phylogenetic relationships between individuals, thus controlling for the use of breed standard metrics. We observe that biological age methylation clocks are affected by population stratification and require heavy parameterization to achieve effective predictions. Finally, we observe that methylation-related markers reflecting biological age signals are rare and do not colocalize between datasets.