Mazzeo, Robert S., Chakravarthi Rajkumar, Garry Jennings, and Murray Esler. Norepinephrine spillover at rest and during submaximal exercise in young and old subjects. J. Appl. Physiol. 82(6): 1869–1874, 1997.—Aging is associated with elevations in plasma norepinephrine concentrations. The purpose of this investigation was to examine total body and regional norepinephrine spillover as an indicator of sympathetic nerve activity. Eight young (26 ± 3 yr) and seven old (69 ± 5 yr) male subjects were studied at rest and during 20 min of submaximal cycling exercise at 50% of peak work capacity. Norepinephrine spillover was determined by continuous intravenous infusion of [³H]norepinephrine. Arterial norepinephrine concentrations were significantly greater at rest for old vs. young subjects (280 ± 36 vs. 196 ± 27 ng/ml, respectively). Whereas total norepinephrine spillover did not differ between groups at rest, hepatomesenteric norepinephrine spillover was 50% greater in old subjects compared with their young counterparts (51 ± 7 vs. 34 ± 5 ng/min, respectively). Additionally, norepinephrine clearance rates at rest were significantly lower for the old subjects (−23%). During exercise, plasma norepinephrine concentrations increased compared with rest, with old subjects again demonstrating greater values than the young group. Hepatomesenteric norepinephrine spillover was significantly greater (+36%) during exercise for old subjects compared with young; however, no difference was found for whole body spillover rates between age groups. Norepinephrine clearance rates remained depressed (−30%) in the old subjects during exercise. Clearance of epinephrine mirrored that for norepinephrine both at rest and during exercise across age groups. It was concluded that in old subjects, a reduction in norepinephrine clearance and an increase in regional norepinephrine spillover can account for the higher plasma norepinephrine concentrations observed at rest. This relationship is not exacerbated by the stress imposed during an acute bout of exercise.