Determinants of VO2 max decline with aging: an integrated perspective

Aging is associated with a progressive decline in the capacity for physical activity. Central to this decline is a reduction in the maximal rate of oxygen utilization, or VO2 max. This critical perspective examines the roles played by the factors that determine the rate of muscle oxygen delivery versus those that determine the utilization of oxygen by muscle as a means of probing the reasons for VO2 max decline with aging. Reductions in muscle oxygen delivery, principally due to reduced cardiac output and perhaps also a maldistribution of cardiac output, appear to play the dominant role up until late middle age. On the other hand, there is a decline in skeletal muscle oxidative capacity with aging, due in part to mitochondrial dysfunction, which appears to play a particularly important role in extreme old age (senescence) where skeletal muscle VO2 max is observed to decline by approximately 50% even under conditions of similar oxygen delivery as young adult muscle. It is noteworthy that at least the structural aspects of the capillary bed do not appear to be reduced in a manner that would compromise the capacity for muscle oxygen diffusion even in senescence.