DESCRIPTION (Adapted from the Applicant's Abstract): In men and women over the age of 65, the non-acral skin blood flow (SkBF) response to hyperthermia is significantly attenuated. The site of this age-related defect involves the active vasodilator system, a non-adrenergic efferent pathway unique to human skin. The proposed series of studies will systematically examine potential mechanisms through which the negative effects of aging and the positive effects of estrogen therapy are exerted. In older and younger men and women and in post-menopausal women taking various types of hormone replacement therapy or no therapy, the PI plans to (a) examine spatial distribution and heterogeneity of active cutaneous vasodilation to determine whether changes in functional capillary plexus unit density and/or flow contribute to alterations in SkBF using scanning laser-Doppler imaging; (b) examine the magnitude, spatial distribution, and heterogeneity of reflex-mediated noradrenergic cutaneous vasoconstriction during whole-body cooling and baroreceptor unloading using scanning laser-Doppler imaging; and (c) determine the role of nitric oxide (NO) in the control of active vasodilation by examining NO-dependent and independent changes in SkBF during hyperthermia using intradermal microdialysis. In addition, a fourth series of studies is proposed to quantify the upper limit of the prescriptive zone (ULPZ) and age-specific heat exchange coefficients in older versus younger healthy men and women during low-intensity activity. Data from this last proposed investigation operationalizes the SkBF decrement to allow policy-making by health organizations and for modeling biophysical and physiological responses of the elderly to extreme environments.