Uced limb blood flow). 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 (80 mmHg vs. 68 mmHg) [34], 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 [30] 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. 374913-63-0 custom synthesis Several potential mechanisms may explain the association between PP and gait performance. Left ventricular ejection of stroke volume into a stiff aorta (altered aortic 25033180 impedance and subsequent forward wave genesis) coupled with early return of reflected pressure waves of greater magnitude increases cardiac energetic demand, reduces stroke volume (i.e. wave reflections augment pressure but subtract from flow), reduces myocardial oxygen supply/consumption and reduces subendocardial perfusion [35]. Pulsatile pressure and flow damages the endothelium which may alter oxygen delivery to and impair oxygen uptake by the working skeletal muscle [36]. Pulsatile pressure MedChemExpress Methyl linolenate stemming from increased arterial stiffness is associated with retinal damage [37] and visual impairment is a predictor of disability and gait performance [38,39]. Finally, pulsatile load may damage cerebral blood vessels, reduce cerebrovascular reactivity, and contribute to cerebral white matter hyperintensities [40] and cognitive decline [41]. Indeed white matter lesions may be an intermediate factor in the relation of hypertension and lower gait speed in older adults [18,42] and cognitive function 23977191 is associated with physical function [43]. 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 [44] and widening PP. Moreover, increased arterial stiffness, as occurs with natural aging, may exacerbate the influence of HR on wave reflections [45]. 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. Additional research is needed to test this hypothesis empirically. Women had slower 400 m gait speed and this is consistent with previous reports [46,47]. However, sex was not a predictor of gait speed in LIFE-P. A reason for this may be related to concomitant sex-differences in PP. Women had higher PP than men in LIFE-P and this 
is also well established in the literature [48,49]. It is speculated that due to shorter stature and hormonally mediated changes in vascular function, older women have increased arterial stiffness and augmented pressure from wave reflections contributing to higher PP. Interestingly, after adjusting for sex-differences in PP, there were no longer sex-differences in gait speed. Therefore, PP may offer physiolo.Uced limb blood flow). 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 (80 mmHg vs. 68 mmHg) [34], 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 [30] 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 (altered aortic 25033180 impedance and subsequent forward wave genesis) coupled with early return of reflected pressure waves of greater magnitude increases cardiac energetic demand, reduces stroke volume (i.e. wave reflections augment pressure but subtract from flow), reduces myocardial oxygen supply/consumption and reduces subendocardial perfusion [35]. Pulsatile pressure and flow damages the endothelium which may alter oxygen delivery to and impair oxygen uptake by the working skeletal muscle [36]. Pulsatile pressure stemming from increased arterial stiffness is associated with retinal damage [37] and visual impairment is a predictor of disability and gait performance [38,39]. Finally, pulsatile load may damage cerebral blood vessels, reduce cerebrovascular reactivity, and contribute to cerebral white matter hyperintensities [40] and cognitive decline [41]. Indeed white matter lesions may be an intermediate factor in the relation of hypertension and lower gait speed in older adults [18,42] and cognitive function 23977191 is associated with physical function [43]. 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 [44] and widening PP. Moreover, increased arterial stiffness, as occurs with natural aging, may exacerbate the influence of HR on wave reflections [45]. 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. Additional research is needed to test this hypothesis empirically. Women had slower 400 m gait speed and this is consistent with previous reports [46,47]. However, sex was not a predictor of gait speed in LIFE-P. A reason for this may be related to concomitant sex-differences in PP. Women had higher PP than men in LIFE-P and this is also well established in the literature [48,49]. It is speculated that due to shorter stature and hormonally mediated changes in vascular function, older women have increased arterial stiffness and augmented pressure from wave reflections contributing to higher PP. Interestingly, after adjusting for sex-differences in PP, there were no longer sex-differences in gait speed. Therefore, PP may offer physiolo.