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What makes clocks tick? Characterizing developmental dynamics of adult epigenetic clock sites.

ABSTRACT: DNA methylation (DNAm) at specific sites can be used to calculate 'epigenetic clocks', which in adulthood are used as indicators of age(ing). However, little is known about how these clock sites 'behave' during development and what factors influence their variability in early life. This knowledge could be used to optimize healthy aging well before the onset of age-related conditions. Here, we leveraged results from two longitudinal population-based cohorts (N=5,019 samples from 2,348 individuals) to characterize trajectories of adult clock sites from birth to early adulthood. We find that clock sites (i) diverge widely in their developmental trajectories, often showing non-linear change over time; (ii) are substantially more likely than non-clock sites to vary between individuals already from birth, differences that are predictive of DNAm variation at later ages; and (iii) show enrichment for genetic and prenatal environmental exposures, supporting an early-origins perspective to epigenetic aging.

SUBMITTER: Mulder RH

PROVIDER: S-EPMC10979995 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature

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What makes clocks tick? Characterizing developmental dynamics of adult epigenetic clock sites.

Mulder Rosa H RH Neumann Alexander A Felix Janine F JF Suderman Matthew M Cecil Charlotte A M CAM

bioRxiv : the preprint server for biology 20240314

DNA methylation (DNAm) at specific sites can be used to calculate 'epigenetic clocks', which in adulthood are used as indicators of age(<i>ing</i>). However, little is known about how these clock sites 'behave' during development and what factors influence their variability in early life. This knowledge could be used to optimize healthy aging well before the onset of age-related conditions. Here, we leveraged results from two longitudinal population-based cohorts (<i>N</i>=5,019 samples from 2,3 ...[more]

PMID: 38559237

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Project description:BackgroundCardiovascular health (CVH) was defined by the American Heart Association as an integrative idealness of seven clinical or lifestyle factors. Based on populations of European ancestry, recent studies have shown that ideal CVH is associated with a slower aging rate. The aging rate is measured by levels of epigenetic age acceleration (EAA), usually obtained from the residuals of regressing DNA methylation (DNAm) age on chronological age. However, little has been known about the association of CVH with biological aging in Asian populations.Methods and resultsWe here analyzed blood DNAm data and clinical/lifestyle factors of 2474 Taiwan Biobank (TWB) participants, to investigate the association of CVH with EAA. CVH was assessed by seven components: smoking status, physical activity, dietary habits, body mass index, total cholesterol, fasting glucose, and blood pressure levels. Four measures of EAA were applied, among which two were based on the first-generation DNAm clocks (HannumEAA and IEAA) and two were based on the second-generation clocks (PhenoEAA and GrimEAA). After excluding 276 individuals with cardiovascular diseases, we regressed EAA on the CVH score (ranging from 0 to 7, integrating the abovementioned seven components) while adjusting for sex, drinking status, and educational attainment. Our results showed that a decrease in one point in the CVH score was associated with a 0.350-year PhenoEAA (p = 4.5E-4) and a 0.499-year GrimEAA (p = 4.2E-15). By contrast, HannumEAA and IEAA were not significantly associated with the CVH score. We have obtained consistent results within each generation of epigenetic clocks.ConclusionsThis is one of the first studies to comprehensively investigate the associations of CVH with four epigenetic clocks. Our TWB data showed that ideal CVH is associated with lower levels of EAA calculated according to the second-generation epigenetic clocks (PhenoEAA and GrimEAA). Having an ideal CVH status can lower EAA and reduce the risk of aging-related disorders.

Dataset Information

What makes clocks tick? Characterizing developmental dynamics of adult epigenetic clock sites.

Publications

What makes clocks tick? Characterizing developmental dynamics of adult epigenetic clock sites.

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