OF WORK Our laboratory has utilized multiple techniques to determine the effects of age, gender, and lifestyle on resting and exercise cardiovascular (CV) performance. (A) Longitudinal changes of maximal aerobic capacity (VO2max) were determined in nearly1,400 Baltimore Longitudinal Study of Aging (BLSA) volunteers without evident cardiac disease, using mixed effects statistical analysis. Per decade longitudinal declines in VO2max were generally greater than cross-sectional declines, especially in older age decades. Gender differences in both absolute VO2max and rates of decline (men>women) were markedly attenuated when VO2max was normalized for fat-free mass rather than body weight. Thus, cross-sectional estimates of aerobic capacity age changes significantly underestimate longitudinal declines in older subjects. (B) To examine longitudinal changes in CV performance during aerobic exercise, we performed serial gated cardiac scans (Tc-99m) during maximal upright cycle ergometry in 33 healthy BLSA men at a mean interval of 10.3 years. Significant longitudinal declines of peak work rate (7%), heart rate (10%), left ventricular (LV) ejection fraction (5%) and cardiac index (9%) were observed; however stroke volume index at exhaustion remained unchanged. These findings parallel and confirm age-associated changes in exercise CV performance derived from cross-sectional studies. (C) To determine the effect of endurance training on endothelial-dependent (ED) and non-endothelial dependent (non ED) arterial dilation, we compared brachial artery vasodilator responses to reactive hypertension and sublingual nitroglyercin in endurance trained older men and their sedentary age peers. Despite similar coronary risk profiles, the athletes demonstrated 40% greater vasodilator responses to both stimuli than did the sedentary controls. By multiple regression analysis, VO2max was a strong independent predictor of both ED and non ED vasodilation. Thus, endurance training enhances arterial dilation in older men.