Doctoral Dissertation Research: Quantifying the Costs of Human Reproduction using the 'Epigenetic Clock'

The idea that reproduction carries costs that compete with somatic maintenance and lifespan is foundational to life history theory and human reproductive ecology. Despite their theoretical importance, the costs of reproduction (CoR) in women are poorly understood. A major challenge when testing for CoR traces to the fact that women can vary markedly in factors like resource availability or health, which can obscure tradeoffs. This confounding can make it difficult to determine whether reproduction carries costs, or if individuals with higher somatic costs for other reasons invest more in reproduction. An additional challenge stems from the need to employ a biomarker that captures the cumulative impact of reproduction while accurately predicting subsequent health and mortality risk. To address these gaps, we propose to use the 'epigenetic clock' - a new, highly accurate marker of aging and molecular senescence - to examine CoR in female participants in a well-characterized longitudinal study in Cebu, Philippines. The proposed study will build on data collected in 2005, which reveals preliminary evidence for epigenetic age acceleration (AgeAccel) in relation to parity in female participants during early adulthood (20-22 years old). We propose a second measure of epigenetic age 13 years later, which will allow us to track individual changes in AgeAccel as they relate to concurrent reproductive effort. This longitudinal design will allow us to explore the predictors of within-individual changes in Age Accel, thereby minimizing confounding by individual-level differences in health or resource access. These analyses will be complemented by epigenetic age measurement in the participants' post-reproductive mothers (47-72 years old) for whom we also have complete reproductive histories, and who have recently completed a 5-year study of health and aging. Taken together, this study will allow for a longitudinal assessment of the link between reproductive effort and epigenetic AgeAccel in young women, while clarifying the impacts of reproduction on aging in their post-reproductive mothers, providing rigorous assessment of the CoR in a living human population.