Sex-specific Influence of Aging on Exercising Leg Blood Flow

PURPOSE: Our previous work suggests that healthy human aging is associated with sex-specific differences in leg vascular responses during large muscle mass exercise (two-leg cycling). The present study determined if age by sex interactions in exercising leg hemodynamics persist during small muscle mass exercise that is not limited by cardiac output. METHODS: Thirty-one young (15 men [mean ± S.E.M]: 24 ± 1 yrs; 16 women: 22 ± 1 yrs) and thirty-one older (13 men: 71 ± 2 yrs; 18 women: 67 ± 1 yrs) healthy, normally active adults performed graded single leg knee extensions to maximal exertion. Femoral artery blood velocity and diameter (Doppler ultrasound), heart rate (ECG) and beat-to-beat arterial blood pressure (MAP, radial artery tonometry) were measured during each 3-min work rate (4.8 and 8 watts/stage for women and men, respectively). RESULTS: Despite reduced resting leg blood flow and vascular conductance, older men exhibited preserved exercising leg hemodynamic responses. Older women, by contrast, exhibited attenuated hyperemic (Young: 52 ± 3 mL min−1 W−1; vs Older: 40 ± 4 mL min−1 W−1; p = 0.02) and vasodilatory responses (Young: 0.56 ± 0.06 mL min−1 mmHg−1 W−1 vs Older: 0.37 ± 0.04 mL min−1 mmHg−1 W−1; p< 0.01) to exercise compared to younger women. Relative (% of maximal) work rate comparisons of all groups combined also revealed attenuated vasodilator responses in older women (p<0.01 for age*sex*work rate interaction). These sex-specific age differences were not abolished by consideration of hemoglobin, quadriceps muscle mass, muscle recruitment or mechanical influences on muscle perfusion. In addition, fitness (VO2max) was at least a marginally significant covariate (all p< 0.09) in the relation between work rate and either leg blood flow or vascular conductance in all groups except older women. In the same model, accelerometer-derived measures of physical activity were also significant covariates in young (both p<0.01) but not older (both p> 0.20) women. CONCLUSIONS: Collectively, these findings suggest that local factors underlie the sex-specific effects of aging on exercising leg hemodynamics in healthy adults. Furthermore, the modulation of leg hemodynamic responses to exercise by chronic fitness or physical activity appears to be lost with age in women.