Age and early life adversity shape heterogeneity of the epigenome across tissues in macaques

Sadoughi, B., Petersen, R., Patterson, S. K., Slikas, E., Adjandba, C., Ryan, N., Costa, C. E., Newman, L. E., Watowich, M. M., Kelsey, C. R., Greenier, A., Goldman, E. A., Negron-Del Valle, J. E., Phillips, D., Thompson, I., Surratt, S. E. B., Gonzalez, O., Compo, N. R., Burgos-Rodriguez, A. G., Cayo Biobank Research Unit, , DeCasien, A. R., Chiou, K. L., Walker, C. S., Lambides, A. V. R., Martinez, M. I., Sterner, K. N., Brent, L. J. N., Higham, J. P., Montague, M. J., Platt, M. L., Snyder-Mackler, N., Lea, A. J.

Vanderbilt University · biorxiv

Paper

Abstract

Age and early life adversity (ELA) are both key determinants of health, but whether they target similar physiological mechanisms across the body is unknown due to limited multi-tissue datasets from well-characterized cohorts. We generated DNA methylation (DNAm) profiles across 14 tissues in 237 semi-free ranging rhesus macaques, with records of naturally occurring ELA. We show that age-associated DNAm variation is predominantly tissue-dependent, yet tissue-specific epigenetic clocks reveal that the pace of epigenetic aging is relatively consistent within individuals. ELA effects on loci are adversity-dependent, but a given ELA has a coordinated impact across tissues. Finally, ELA targeted many of the same loci as age, but the direction of these effects varied, indicating that ELA does not uniformly contribute to accelerated age in the epigenome. ELA thus imprints a coordinated, tissue-spanning epigenetic signature that is both distinct from and intertwined with age-related change, advancing our understanding of how early environments sculpt the molecular foundations of aging and disease.

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Research summary

The paper claims that early life adversity and age shape a coordinated epigenetic signature across tissues, influencing the molecular foundations of aging and disease. This research is relevant as it explores the underlying mechanisms of aging and how early environmental factors can affect epigenetic changes related to health outcomes.

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