Elevated PP is also an independent predictor of gait speed in older adults, a measure of physical function that in and of itself is a predictor of survival in older adults. Older adults with higher PP had PR-171 significantly slower gait speed compared to older adults with lower PP. These findings raise the intriguing possibility that ageassociated decline in vascular function may be inextricably linked to decline in physical function. In well-functioning older adults, PP/arterial stiffness may not be a predictor of short distance gait speed. Our findings are consistent with this as we noted no association between PP and 4 m gait speed in older adults with mobility limitations from the LIFE-P cohort. We noted an association between long distance gait speed and PP in older adults with mobility limitations. Recent work from the Health Aging and Body Composition Study has noted that arterial stiffness is a predictor of gait speed in older adults with peripheral arterial disease. Previous studies have noted that arterial stiffness and pressure from wave reflections are also predictors of walking distance in patients with PAD. Recently, our group has reported an association between PP and long-distance gait performance in adults with multiple sclerosis. Mobility limitations, as seen with PAD and MS, perpetuate a sedentary lifestyle and physical inactivity is a potent instigator of vascular mal-adaptation. Older adults with mobilitylimitations from LIFE-P with the slowest gait speed had substantially higher pulse pressure than older well-functioning adults from the Health ABC Study, suggesting hastened vascular senescence in the LIFE-P group. Thus our findings support previous conclusions that arterial stiffness may be especially detrimental to older adults with established compromised mobility and significantly impaired vascular function and suggest that long distance gait performance but not short distance gait performance may be influenced by PP in older adults at risk for mobility disability. Several potential mechanisms may explain the association between PP and gait performance. Left ventricular ejection of stroke volume into a stiff aorta coupled with early return of reflected pressure waves of greater magnitude increases cardiac energetic demand, reduces stroke volume, reduces myocardial oxygen supply/consumption and reduces subendocardial perfusion. Pulsatile pressure and flow damages the endothelium which may alter oxygen delivery to and impair oxygen uptake by the working skeletal muscle. Finally, pulsatile load may damage cerebral blood vessels, reduce cerebrovascular reactivity, and contribute to cerebral white matter hyperintensities and cognitive decline. Indeed white matter lesions may be an intermediate factor in the relation of hypertension and lower gait speed in older adults and cognitive function is associated with physical function. Older adults taking beta-blockers had higher PP and a trend toward lower gait speed than older adults not taking these agents. This appears to have been mediated by the secondary effect of beta-blockers on heart rate as heart rate was significantly lower in those taking beta-blockers versus those not taking these agents. Adjusting for heart rate abolished differences in PP and gait speed. Reductions in heart rate with beta-blocker use may alter pressure wave temporal associations, increasing late systolic pressure augmentation and widening PP. Moreover, increased arterial stiffness, as occurs with natural aging, may exacerbate the influence of HR on wave reflections. Thus, therapies that negatively influence pressure from wave reflections and increase PP may have a detrimental effect on physical function in older adults with low already low vascular compliance.