Abstract
Variation in healthy aging and lifespan is ascribed more to various non-genetic factors than to inherited genetic determinants, and a major goal in aging research is to reveal the epigenetic basis of aging. One approach to this goal is to find genomic sites or regions where DNA methylation correlates with biological age. Using health data from 134 elderly twins, we calculated a frailty index as a quantitative indicator of biological age, and by applying the Infinium HumanMethylation450K BeadChip technology to their leukocyte DNA samples, we obtained quantitative DNA methylation data on genome-wide CpG sites. We analyzed the health and epigenome data by taking two independent associative approaches: the parametric regression-based approach and a non-parametric machine learning approach followed by GO ontology analysis. Our results indicate that DNA methylation at CpG sites in the promoter region of PCDHGA3 is associated with biological age. PCDHGA3 belongs to clustered protocadherin genes, which are all located in a single locus on chromosome 5 in human. Previous studies of the clustered protocadherin genes showed that (1) DNA methylation is associated with age or age-related phenotypes; (2) DNA methylation can modulate gene expression; (3) dysregulated gene expression is associated with various pathologies; and (4) DNA methylation patterns at this locus are associated with adverse lifetime experiences. All these observations suggest that DNA methylation at the clustered protocadherin genes, including PCDHGA3, is a key mediator of healthy aging.
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References
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Acknowledgments
We thank participants in our studies. We also thank the Mid-Atlantic Twin Registry at Virginia Commonwealth University and the University of Washington Twin Registry for recruiting twins and collecting health data.
Funding
This study was supported by the National Institute of General Medical Sciences of the National Institutes of Health (P20GM103629) to S.M.J. and S.K.
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Kim, S., Wyckoff, J., Morris, AT. et al. DNA methylation associated with healthy aging of elderly twins. GeroScience 40, 469–484 (2018). https://doi.org/10.1007/s11357-018-0040-0
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DOI: https://doi.org/10.1007/s11357-018-0040-0