Thomas W. McDade, Calen P. Ryan, Linda S. Adair, Nanette R. Lee, Delia B. Carba, Julia L. MacIsaac, Kristy Dever, Parmida Atashzay, Michael S. Kobor, Christopher W. Kuzawa
Objectives: The drivers of human life expectancy gains over the past 200 years are not well-established, with a potential role for historical reductions in infectious disease. We investigate whether infectious exposures in infancy predict biological aging using DNA methylation-based markers that forecast patterns of morbidity and mortality later in life. Methods: N = 1450 participants from the Cebu Longitudinal Health and Nutrition Survey—a prospective birth cohort initiated in 1983—provided complete data for the analyses. Mean chronological age was 20.9 years when venous whole blood samples were drawn for DNA extraction and methylation analysis, with subsequent calculation of three epigenetic age markers: Horvath, GrimAge, and DunedinPACE. Unadjusted and adjusted least squares regression models were evaluated to test the hypothesis that infectious exposures in infancy are associated with epigenetic age. Results: Birth in the dry season, a proxy measure for increased infectious exposure in the first year of life, as well as the number of symptomatic infections in the first year of infancy, predicted lower epigenetic age. Infectious exposures were associated with the distribution of white blood cells in adulthood, which were also associated with measures of epigenetic age. Conclusions: We document negative associations between measures of infectious exposure in infancy and DNA methylation-based measures of aging. Additional research, across a wider range of epidemiological settings, is needed to clarify the role of infectious disease in shaping immunophenotypes and trajectories of biological aging and human life expectancy. © 2023 The Authors. American Journal of Human Biology published by Wiley Periodicals LLC.
Department of Anthropology, Northwestern University, Evanston, IL, United States; Institute for Policy Research, Northwestern University, Evanston, IL, United States; Robert N. Butler Columbia Aging Center, Department of Epidemiology, Columbia University Mailman School of Public Health, New York, NY, United States; Department of Nutrition, Gillings School of Global Public Health, Carolina Population Center, CB #8120, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States; Office of Population Studies Foundation, University of San Carlos, Cebu City, Philippines; Department of Medical Genetics, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada; Edwin S.H. Leong Centre for Healthy Aging, University of British Columbia, Vancouver, BC, Canada; Centre for Molecular Medicine and Therapeutics, Vancouver, BC, Canada
