Effects of environmental adversity on molecular aging in the immune system of companion dogs

Abstract Aging exhibits remarkable individual heterogeneity as exemplified by the varying health trajectories and outcomes experienced by people of the same chronological age. Much of this variability is due to different live experiences and environments. Understanding the impact of environmental factors on aging is essential because it holds the key to unlocking strategies for promoting healthier and more equitable aging experiences for individuals across diverse backgrounds. The F99 phase of this project explores the interplay between environmental adversity, epigenetic shifts, and aging, using a cohort of 1,000 dogs from the Dog Aging Project. The goal is to understand how environmental factors modulate the epigenome, potentially accelerating aging and influencing health and lifespan. Specifically, I am analyzing associations between age, sex, weight, and site-specific and global DNA methylation changes, alongside validating a DNA methylation-based 'epigenetic clock' associated with chronological age, and assessing whether environmental adversity mirrors molecular aging. At the end of the F99 phase, I will have revealed mechanisms behind environmentally-induced aging in dogs, and gained training and expertise that will serve as a bridge to the postdoctoral, K00 phase. In the K00 phase, my research will expand to explore molecular determinants of aging in women, with an emphasis on understanding how specific environmental adversities impact their aging processes. Utilizing data from extensive cohort studies like the Study of Women's Health Across the Nation study (SWAN), a long-term cohort study that investigates the physical, psychological, and social aspects of women's health during the menopausal transition and beyond, involving a diverse group of women across different racial and ethnic backgrounds. I aim to uncover how epigenetics, and gender-specific environmental adversity intertwine to define aging trajectories in women, with the goal to identify high-risk groups and develop targeted interventions, thereby ameliorating age-related disparities and enhancing health and longevity in women.