Women’s Health and Aging: Developmental Pathways Underlying Life Course Risk

The current application is responsive to the NIH-Wide Strategic Plan for Research on the Health of Women (2024-2028) led by the Office of Research on Women’s Health. It addresses Strategic Goal 1 (Research) under Objective 6 to advance women’s health through the study of key transition periods. Here, we focus on female pubertal development because of its impact on post-pubertal health and its potential to be targeted as a strategy for intervention to improve the long-term health of women. Earlier maturing girls are at risk for numerous emotional and social harms and for poor physical health, including the early emergence and worsening of cardiometabolic risk factors and increases in risk for obesity, type 2 diabetes, cardiovascular disease, and early mortality. Moreover, pubertal onset is hastened by prepubertal exposures such as excess body weight and adverse early life experiences. Yet, as evidence mounts revealing critical life course links between early life exposures, pubertal onset, and women’s cardiometabolic health, there are significant knowledge gaps about the mechanisms that account for these associations. Notably, the timing of pubertal onset has been hypothesized to itself mark aging, indicating the pace at which key social and biological milestones are met. However, few studies have examined this possibility directly by evaluating associations between pubertal timing and biological aging. Recent advances in biological aging biomarkers now make testing this hypothesis possible. The current study seeks NIH funding to recruit the female participants in the landmark birth cohort NICHD Study of Early Child Care and Youth Development (SECCYD) (expected: n=374; 80% return of 468; mean age=38 [35-40 yrs]) to complete a second FU visit (FU2), modelled after the first FU visit (FU1) which had an 81% return (n=378; mean age=28 [26-31 yrs]). This new FU2 data will be integrated with the original SECCYD and FU1 data, leveraging prospective (birth to midlife) gold standard measures, including Tanner staging for the assessment of pubertal maturation and epigenetic and ovarian aging biomarkers for the assessment of biological aging. A series of life course models will then be tested to determine whether the timing and pace of female pubertal maturation predicts worsening cardiometabolic health and accelerated biological aging both directly and as a mediator of effects of adverse prepubertal exposures. Models will also test whether the risk associated with these direct and indirect effects may be partially offset by post-pubertal protective factors (e.g., adult socioeconomic status, health behaviors, and psychological health) and whether accelerated biological aging may partially account for effects of earlier and faster pubertal maturation on worsening cardiometabolic health. Gaining new knowledge about whether pubertal maturation impacts the biological aging processes that underlie disease and mortality outcomes will inform opportunities for puberty-focused interventions to slow biological aging and prevent disease broadly. This work addresses the urgent need to enhance health and lengthen healthspan in women who, despite living longer than men, experience significantly more years of disability and are at increased risk for multimorbidity. Project Number: 1R01AG098430-01 | Fiscal Year: 2026 | NIH Institute/Center: National Institute on Aging (NIA) | Principal Investigator: Maria Bleil | Institution: UNIVERSITY OF WASHINGTON, SEATTLE, WA | Award Amount: $651,175 | Activity Code: R01 | Study Section: Aging, Injury, Musculoskeletal, and Rheumatologic Disorders Study Section[AIMR] View on NIH RePORTER: https://reporter.nih.gov/project-details/11275336