Decreased maximal heart rate with aging is related to reduced β-adrenergic responsiveness but is largely explained by a reduction in intrinsic heart rate

A decrease in maximal exercise heart rate (HRmax) is a key contributor to reductions in aerobic exercise capacity with aging. However, the mechanisms involved are incompletely understood. We sought to gain insight into the respective roles of intrinsic heart rate (HRint) and chronotropic beta-adrenergic responsiveness in the reductions in HRmax with aging in healthy adults. HRmax (Balke treadmill protocol to exhaustion), HRint (HR during acute ganglionic blockade with intravenous trimethaphan), and chronotropic beta-adrenergic responsiveness (increase in HR with incremental intravenous infusion of isoproterenol during ganglionic blockade) were determined in 15 older (65 +/-5 yr) and 15 young (25 +/-4 yr) healthy men. In the older men, HRmax was lower (162 +/-9 vs. 191 +/-11 beats/ min, P < 0.0001) and was associated with a lower HRint (58 +/-7 vs. 83 +/-9 beats/ min, P < 0.0001) and chronotropic beta-adrenergic responsiveness (0.094 +/-0.036 vs. 0.154 +/-0.045 Delta HR/[isoproterenol]: P < 0.0001). Both HRint (r = 0.87, P < 0.0001) and chronotropic beta-adrenergic responsiveness (r = 0.61, P < 0.0001) were positively related to HRmax. Accounting for the effects of HRint and chronotropic beta-adrenergic responsiveness reduced the age-related difference in HRmax by 83%, rendering it statistically nonsignificant (P = 0.2). Maximal oxygen consumption was lower in the older men (34.9 +/-8.1 vs. 48.6 +/-6.7 ml.kg(-1).min(-1), P < 0.0001) and was positively related to HRmax (r = 0.62, P < 0.0001), HRint (r = 0.51, P = 0.002), and chronotropic beta-adrenergic responsiveness (r = 0.47, P = 0.005). Our findings indicate that, together, reductions in HRint and chronotropic responsiveness to beta-adrenergic stimulation largely explain decreases in HRmax with aging, with the reduction in HRint playing by far the greatest role.