PROJECT SUMMARY Heat waves are the deadliest natural disaster and disproportionately affect the health of the elderly. This increased mortality and morbidity in the elderly is primarily cardiovascular in origin. However, our current understanding of the cardiovascular responses of the elderly to heat stress is limited to non-physiological models. Therefore, the overall objective of this work is to identify markers of increased cardiovascular and thermoregulatory stress during heat wave-like conditions in the elderly. Aim 1 will assess the cardiovascular responses of the elderly to heat wave conditions. Specifically, we hypothesize that elderly participants, aged older than 65, will demonstrate impaired cardiovascular responses during simulated heat wave conditions compared to younger adults. We will comprehensively assess the cardiovascular and thermal responses of elderly participants and younger adults exposed to two heat wave conditions, hot and humid (replicating the 1995 Chicago heat wave), hot and dry (replicating the 2018 Los Angeles heat wave). Aim 2 will determine predictors of poor cardiovascular and thermoregulatory responses to heat wave conditions in the elderly. We anticipate that inter-individual variations in resting cardiovascular function can be used to predict poor thermoregulatory and cardiovascular responses to simulated heat wave conditions in elderly participants. Using an exploratory predictive modeling approach to analyze the data from Aim 1, we will identify baseline and demographic factors that predict poor responses to heat stress in the elderly. The expected outcomes of this work will establish foundational knowledge of the cardiovascular and thermoregulatory consequences of heat waves for the elderly, that can be used to target future strategies and therapies to help reduce the health risks to this vulnerable population.