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 β-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 β-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 β-adrenergic responsiveness (0.094 ± 0.036 vs. 0.154 ± 0.045 ΔHR/[isoproterenol]: P < 0.0001). Both HRint ( r = 0.87, P < 0.0001) and chronotropic β-adrenergic responsiveness ( r = 0.61, P < 0.0001) were positively related to HRmax. Accounting for the effects of HRint and chronotropic β-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 β-adrenergic responsiveness ( r = 0.47, P = 0.005). Our findings indicate that, together, reductions in HRint and chronotropic responsiveness to β-adrenergic stimulation largely explain decreases in HRmax with aging, with the reduction in HRint playing by far the greatest role.
Mammalian γ2 AMPK regulates intrinsic heart rate
