PROJECT SUMMARY/ABSTRACT This proposal directly addresses, in a uniquely innovative and direct approach, the stated goal of FAO PAR-19- 250: To better understand “exposure of the older person to changing environmental hazards in their daily environment that raises their risks”. Men and women over the age of 65 are the most vulnerable population during severe environmental heat events. While we know a lot about age-related declines in physiological responses to environmental heat stress, there are key critical gaps in our understanding of the impact of extreme weather on aging human populations as well as in ways to positively intervene. The present project adds practical information: 1) by determining the integrated thermoregulatory response of men and women over the age of 65 yrs to a wide variety of adverse environments and 2) by identifying the specific environments that have significant adverse impact on older adults. The research approach will yield directly translatable results that can be used for evidence-based alert communication, policy decisions, triage for impending heat events, and implementation of other safety interventions. We will test the global hypothesis that aging will shift critical environmental limits to a narrower range of safe environments across the psychometric spectrum (encompassing warm-humid to hot-dry environments). The present proposal logically builds on our 30-year body of mechanistic research on thermoregulation and aging and our experience in executing this unique research paradigm. In Specific Aim 1 we propose to identify those environmental limits above which age-related physiological changes cause uncompensable heat stress, resulting in heat storage and increasing the risk of heat illness. As appropriate based on the data, distinct psychrometric limits will be derived for older men and older women. We hypothesize that aging will decrease critical environmental heat balance limits, particularly in warm-dry environments due to impairments in sweating mechanisms. In Specific Aim 2 we will calculate critical evaporative coefficients and wet-bulb globe temperature isotherms that can be used to predict environmental conditions that are uncompensable, and therefore increase health risks for older men and women. These coefficients can subsequently be used to predict responses of older adults to a wider set of environmental parameters (solar load, wind, etc.). Finally, we propose one additional exploratory Aim. Our laboratory has identified additional detrimental effects of over-the-counter and commonly prescribed platelet inhibitors on thermoregulation in older men and women. We have previously described how aspirin (ASA) and prescription platelet inhibitors (clopidogrel; Plavix®) further accelerate the rise in body core temperature in warm environmental conditions and impairs heat loss mechanisms. Therefore, we propose to also determine the effects of ASA on age-specific critical environmental limits, hypothesizin...