PROJECT SUMMARY (RESEARC PROJECT 2: The Role of Adaptation and Resilience in a Changing Climate: Cardiovascular Risk and Allostatic Load Among Youth) Climate change (CC) is rapidly intensifying, and while mitigating CC is a critical goal, there is an urgent need to reduce vulnerability to its cardiovascular health (CVH) impacts. Of the rapidly emerging CC threats, heat stress and wildfire (WF) smoke are strongly linked to adverse CVH outcomes, yet little is known about how CC may influence CVH profiles across the age spectrum, particularly in youth when adaptation strategies to increase resilience may be most impactful on long term health. Growing evidence indicates measures of CVH in youth are associated with cardiovascular endpoints and events in adulthood. While studies have linked air pollution exposures with early cardiovascular changes in youth, less is known about WF smoke, heat stress, and how co- exposure may influence these relationships. This question is critical for individuals and communities with lower CC adaptive capacity and resilience which helps withstand and quickly recover from CC-related hazards. Allostatic load (AL) correlates with reduced biological resilience to the effects of environmental exposures and stressors. The AL model posits repeated chronic exposure to (or anticipation of) hazards and stressors – similar to those experienced with CC - can dysregulate the body's adaptive systems leading to “wear and tear” on organ systems and greater risk of adverse outcomes over the life course, including CVH. Recent evidence has linked CC with stress, anxiety, and mental health impacts due to experiencing or anticipating CC hazards; however, few studies have begun to conceptualize AL's role in CC adaptation and resilience. We hypothesize AL may serve as a sensitive early indicator of individual, biological resilience to CC-related heat stress and WF smoke exposures and risk of adverse CVH across the life course. We will investigate these questions in the MetaAir2 cohort, a subset of the Southern California Children's Health Study with 20+ years of active follow-up and comprehensive CVH assessment of young adults starting in childhood. We aim to understand how lifetime heat stress and WF smoke exposure independently and jointly impacts blood pressure and pulse rate over time (Aim 1), and AL (Aim 2) in adulthood. We will assess whether neighborhood climate adaptation vulnerabilities (e.g., urban heat islands, tree canopies, climate and social vulnerability indices) could modify risk (Aim 3). We will investigate the association between AL and carotid ultrasound measures of vascular injury in adulthood to inform AL's utility as an early marker of adverse CVH outcomes and a precision screening measure of individual biological resilience to CC (Sub-Aim). Developing a greater understanding of CVH impacts of lifetime heat stress and WF smoke and AL's utility as a personalized measure of biological resilience to CC can inform targeted a...