Epigenetic aging, social factors, and preterm birth among Black women - PROJECT ABSTRACT Preterm birth (PTB; <37 weeks gestation) is the leading cause of infant mortality among Black infants. Maternal chronological age has long been used to assess risk for PTB; however, chronological age assumes that individuals age at similar rates and does not capture the inter-individual differences that may exist due to race. Although both Black and White women have a maternal age-related increase in PTB, the risk for PTB is higher among Black women than among White women at all maternal ages. Geronimus’ weathering hypothesis describes a pattern in which age-related increases in PTB occur at a younger age for Black women, and risk with age increases in a linear pattern, rather than the J- shaped association with chronological age overall. This acceleration of aging has been attributed to Black women being more likely to experience chronic stress due to social stressors of racial discrimination and neighborhood disorder and crime. Epigenetic age, a measure of cellular or biological aging, reflects influences of past exposures and may be more useful in determining risk for PTB than chronological age, which is uniform regardless of life experiences. However, research is lacking on (1) the association of social stressors with epigenetic aging among Black pregnant women; and (2) the association of epigenetic aging with PTB among these women. This study is designed to address the gaps in prior research and relies on our previous work demonstrating that ribosomal DNA methylation (rDNAm) harbors the rDNA clock, a novel, sensitive, and evolutionarily conserved clock of epigenetic aging. The goal of this study is to examine epigenetic aging as a marker of social stressors and a biomarker indicating risk of PTB among Black women. Our cohort is comprised of 550 Black pregnant women enrolled prior to the COVID-19 pandemic from the Detroit, MI and Columbus, OH areas (R01 MD011575, PI Giurgescu). Women completed questionnaires and provided whole blood samples and saliva during pregnancy, and these biological samples will be used to complete the proposed study. Maternal medical records have been abstracted. We aim to: (Aim 1) Determine whether social stressors are associated with an accelerated rDNAm clock among Black pregnant women; (Aim 2) Determine whether women with PTB have an accelerated rDNAm clock compared with women with term birth; and (Aim 3) Assess performance of the rDNAm clock associated with PTB relative to alternative metrics of epigenetic aging. Epigenetic age, a biological reflection of inter- individual variability in aging, holds significant potential as a useful parameter in PTB prevention from a precision health perspective. Currently, the ability to predict PTB is poor, especially among Black women. Precision health has the potential to identify individual women who are at risk for PTB, and to identify therapeutic targets to prevent an individual from having PTB.