Longitudinal decline in peak V̇o 2 with aging in a healthy population is associated with a reduction in peripheral oxygen utilization but not in cardiac output.

Aging is associated with a significant decline in aerobic capacity assessed by maximal exercise oxygen consumption (V̇o _2max ). The relative contributions of the specific V̇o ₂ components driving this decline, namely cardiac output (CO) and arteriovenous oxygen difference (A - V)O ₂ , remain unclear. We examined this issue by analyzing data from 99 community-dwelling participants (baseline age: 21-96 yr old; average follow-up: 12.6 yr old) from the Baltimore Longitudinal Study of Aging, free of clinical cardiovascular disease. V̇o _2peak , a surrogate of V̇o _2max , was used to assess aerobic capacity during upright cycle ergometry. Peak exercise left ventricular volumes, heart rate, and CO were estimated using repeated gated cardiac blood pool scans. The Fick equation was used to calculate (A - V)O _{2 diff,peak} from CO _peak and V̇o _2peak . In unadjusted models, V̇o _2peak , (A - V)O _{2 diff,peak} , and CO _peak declined longitudinally over time at steady rates with advancing age. In multiple linear regression models adjusting for baseline values and peak workload, however, steeper declines in V̇o _2peak and (A - V)O _{2 diff,peak} were observed with advanced entry age but not in CO _peak . The association between the declines in V̇o _2peak and (A - V)O _{2 diff,peak} was stronger among those ≥50 yr old compared with their younger counterparts, but the difference between the two age groups did not reach statistical significance. These findings suggest that age-associated impairment of peripheral oxygen utilization during maximal exercise poses a stronger limitation on peak V̇o ₂ than that of CO. Future studies examining interventions targeting the structure and function of peripheral muscles and their vasculature to mitigate age-associated declines in (A - V)O _{2 diff} are warranted. NEW & NOTEWORTHY The age-associated decline in aerobic exercise performance over an average of 13 yr in community-dwelling healthy individuals is more closely associated with decreased peripheral oxygen utilization rather than decreased cardiac output. This association was more evident in older than younger individuals. These findings suggest that future studies with larger samples examine whether these associations vary across the age range and whether the decline in cardiac output plays a greater role earlier in life. In addition, studies focused on determinants of peripheral oxygen uptake by exercising muscle may guide the selection of preventive strategies designed to maintain physical fitness with advancing age.