Psychosocial Stress in Early Life, Chronodisruption and Accelerated Aging in Mid Life: A Life-course Approach

As the U.S. population ages, the burden of chronic disease and disability is increasing. It is important to note that because this burden arises from multiple aging-related conditions, prevention or treatment strategies directed at a single disease may not fully address the challenge. Instead, it has become clear that a more effective strategy for extending healthy lifespan is to slow the aging process itself. Increasing evidence indicates that early-life adverse experiences play a critical role in shaping long-term health trajectories and may accelerate biological aging. However, the mechanisms through which early life stress becomes behaviorally and biologically embedded to influence aging trajectories remain poorly understood. Chronodisruptive behaviors, such as irregular sleep patterns, late meal timing, and disrupted rest–activity rhythms, are increasingly prevalent in modern society and are linked to adverse aging-related outcomes, including cardiovascular disease and cognitive decline. These behaviors may represent a critical pathway connecting early-life stress to accelerated aging. Notably, the stress-response system is closely interconnected with the circadian timing system, suggesting that circadian dysfunction may be a central biological mechanism underlying this relationship. Despite this, few longitudinal studies have comprehensively examined chrono-behaviors and circadian biomarkers in relation to aging outcomes across the life course. This project will test the hypothesis that chronodisruptive behaviors and circadian dysfunction may contribute as key mechanisms through which early-life stress becomes behaviorally and biologically embedded, ultimately accelerating aging in midlife. We will leverage two well-established longitudinal cohorts which have followed over 1,000 participants from childhood into midlife with repeated, multidimensional assessments of early-life stress. As participants enter midlife (ages 32–58), recent and planned follow-up visits include detailed measures of chrono-behaviors, circadian biomarkers (including melatonin and cortisol), and aging-related outcomes such as biological age, vascular function, and cognitive performance. Aim 1 will examine whether early-life stress experienced during the first 25 years of life is associated with chronodisruptive behaviors, and whether these behaviors contribute to accelerated biological aging and declines in vascular and cognitive function in midlife. Aim 2 will test whether circadian dysfunction, indexed by reduced melatonin secretion and altered diurnal cortisol rhythms, mediates the association between chronodisruptive behaviors and accelerated aging. Aim 3 will test whether race and sex may modify the associations observed in Aims 1 and 2. We will also test whether chronodisruptive behaviors or circadian dysfunction account for observed differences in accelerated-aging risk across race and sex subgroups. This study will clarify how early-life stress shapes aging trajectories and identify modifiable behavioral and circadian targets to improve circadian alignment and promote healthy aging at the population level. Project Number: 1R01AG092807-01A1 | Fiscal Year: 2026 | NIH Institute/Center: National Institute on Aging (NIA) | Principal Investigator: Shaoyong Su (+1 co-PI) | Institution: AUGUSTA UNIVERSITY, AUGUSTA, GA | Award Amount: $646,620 | Activity Code: R01 | Study Section: Lifestyle and Health Behaviors Study Section[LHB] View on NIH RePORTER: https://reporter.nih.gov/project-details/11295586