The aging epidemic has forged interest in patterns and determinants of aging [1], [2], [3]. Recently, social determinants of health have risen to the forefront as important drivers of age-related non-communicable conditions [4], with evidence in humans [5], [6], non-human primates [7], [8], [9] and rodents [8], [10] revealing an indisputable link between unfavorable social experiences and chronic disease risk. The effect of social experiences on health is hypothesized to operate, in part, through epigenetic mechanisms [11], [12], [13]. Of relevance to aging research are genome-wide changes in DNA methylation that occur as individuals get older [14], [15], [16], [17]. Epigenetic clocks are functional biomarkers of developmental and aging processes [18], [19], [20] that capitalize on age-related changes to DNA methylation [21], [22]. One biomarker of recent interest is epigenetic age acceleration (EAA) – that is, the estimated difference between epigenetic age and chronological age – as it outperforms other molecular markers of aging, including telomere length [23] and is a strong predictor of morbidity and mortality [24], [25], [26], [27], [28].

Studies in adults have found that adverse social experiences predict higher EAA [29], [30], [31], [32] with stronger effects observed for experiences occurring earlier versus later in life [30], [33]. Our group recently showed that EAA starts before birth [34], pointing toward the importance of considering how prenatal exposures shape the aging process. To date, only a handful of studies have examined the relationship between maternal social or psychosocial experiences and offspring epigenetic aging. The findings are inconsistent, with some studies indicating faster offspring epigenetic aging following unfavorable maternal experiences, and others suggesting the opposite. In a combined analysis of two cohorts in the Netherlands and Singapore, McGill et al. reported positive associations of maternal prenatal anxiety with higher EAA among male offspring through age 4 years [35]. Similarly, in the U.K.-based Avon Longitudinal Study of Parents and Children cohort, maternal adverse childhood experiences (ACEs) predicted higher offspring EAA at birth, again primarily in males [36]. On the other hand, in the Finnish Prediction and prevention of preeclampsia and intrauterine growth restriction Study, Suarez et al. found that maternal history of pre-pregnancy depression and higher antenatal depressive symptoms were each associated with lower epigenetic gestational age at birth in both sexes [37]. In the California Salinas Valley Center for the Health Assessment of Mothers and Children of Salinas study, Nwanaji-Enweren et al. reported both positive and negative associations of maternal ACEs with offspring epigenetic age acceleration at ages 7, 9, and 14 years, with similar patterns by sex, and also noted that maternal ACEs predicted longer offspring telomere length, indicative of slower biological aging [38]. While the inconsistent findings may reflect differences in specific maternal exposures of interest, method of assessing epigenetic age, and study population characteristics, they also highlight a need for additional research in this area.

In this exploratory pilot study, we investigated associations of maternal social experiences with offspring EAA from birth through mid-childhood among 205 mother-offspring pairs of minoritized racial and ethnic groups. Specifically, we sought to examine associations of maternal experiences of racial bias or discrimination, social support, and indicators of socioeconomic disadvantage during the prenatal period with three measures of EAA at birth and across early and mid-childhood: (1) Horvath’s Pan-Tissue clock, (2) Horvath’s Skin and Blood clock, and the (3) Intrinsic EAA (IEAA) clock. We focus only on mother-offspring pairs from minoritized groups considering the increasingly recognized importance of experiences of racial bias or discrimination on a range of maternal/child outcomes [39], [40] and to reduce the possibility of exposure misclassification among white women who experience bias or discrimination for non-race-related reasons. We hypothesized that maternal experiences of racial bias or discrimination, lower social support, and socioeconomic disadvantage will be associated with persistent differences in offspring EAA across early-life.