Abstract
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.
| Original language | English (US) |
|---|---|
| Article number | e23948 |
| Journal | American Journal of Human Biology |
| Volume | 35 |
| Issue number | 11 |
| DOIs | |
| State | Published - Nov 2023 |
Funding
We thank the researchers at the USC‐Office of Population Studies Foundation, Inc., University of San Carlos, Cebu City, Philippines, for their role in the study design and data collection, and the study participants, who generously provided their time. Research reported in this publication was supported by the National Institute on Aging of the National Institutes of Health (R01 AG061006R21). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. TM gratefully acknowledges financial support from CIFAR as a fellow of the Child and Brain Development program. This research was enabled, in part, by the use of the Software package developed at Dartmouth College, which software is subject to the licensing terms made available by Dartmouth Technology Transfer and which software is provided “AS IS” with no warranties whatsoever. We also would like to thank two anonymous reviewers for thoughtful and constructive comments on our initial submission. We thank the researchers at the USC-Office of Population Studies Foundation, Inc., University of San Carlos, Cebu City, Philippines, for their role in the study design and data collection, and the study participants, who generously provided their time. Research reported in this publication was supported by the National Institute on Aging of the National Institutes of Health (R01 AG061006R21). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. TM gratefully acknowledges financial support from CIFAR as a fellow of the Child and Brain Development program. This research was enabled, in part, by the use of the Software package developed at Dartmouth College, which software is subject to the licensing terms made available by Dartmouth Technology Transfer and which software is provided “AS IS” with no warranties whatsoever. We also would like to thank two anonymous reviewers for thoughtful and constructive comments on our initial submission.
ASJC Scopus subject areas
- Anatomy
- Ecology, Evolution, Behavior and Systematics
- Anthropology
- Genetics