Lazy or old: mitochondria decline in vivo in human muscle similarly with inactivity and age

Abstract

Here we tested the role of lifestyle vs. age using innovative noninvasive tools to measure key mitochondrial functional properties in vivo. Mitochondrial coupling (ATP/O2 or P/O), and phosphorylation capacity (ATPmax) were assessed in human vastus lateralis muscle (VL). Oxidative capacity was biochemically assessed in vitro from biopsies taken from the same site as the in vivo measures. The chronic activity level was measured using a physical activity questionnaire, VO2max test (active >40 ml O2 kg-1 min-1) and verified using a triaxial accelerometer. Subjects were screened to be healthy and disease free and were on average 30 yrs old for the active (n=9) and sedentary (n=18) subjects and 68 yrs old for the elderly (n=30). Mitochondrial coupling in active controls (2.3+0.20, mean+SE) agreed with well-coupled mitochondria (2.3–2.5) but both sedentary (P/O=1.41+0.09) and elderly groups (P/O=1.69+0.11) were substantially uncoupled. Similarly, active subjects had a higher ATPmax (1.11+0.08 mM ATP/sec) than sedentary (0.67+0.03) or aged groups (0.61+0.04). Oxidative capacity was reduced in both groups by 25% relative to active adults. These results demonstrate that mitochondrial properties in vivo drop substantially in sedentary adults and the old. Thus inactivity may be as important as age in the mitochondrial decline found in the elderly. Supported by NIH AG 030226, AR 41928, RC2AG036606, 1P30 DK072476.