The study aimed at determining whether aging and/or sedentariness impairs muscle fat oxidative capacity (OXFA) and whether this was associated with increased risk to develop insulin resistance. We first examined muscle mitochondrial functions, OXFA and insulin sensitivity (ISI; evaluated during an oral glucose tolerance test) in a cross-sectional study with 32 sedentary (S) and endurance-trained (T), young (Y) and elderly (E) men (24.2+/-2.6 vs. 66.6+/-3.2 yr). As for mitochondrial functions, OXFA was higher in T than in S but similar between age groups (SY 41.8+/-11.3, TY 68.0+/-17.7, SE 40.1+/-14.1, TE 73.1+/-20.1 palmitate x min(-1) x g wet tissue(-1); activity P<0.0001, age P=NS, activity x age P=NS). Similar results were obtained with ISI (SY 6.2+/-2.2, TY 11.4+/-4.4, SE 5.9+/-1.5, TE 11.0+/-3.5, activity P<0.001, age P=NS, activity x age P=NS). Stepwise regression showed that, among body composition, VO2max and muscle biochemical characteristics, OXFA was the main predictor of ISI (r=0.60, P<0.001). We subsequently showed in eight sedentary elderly subjects (63.5+/-3.3 yr) that OXFA and insulin sensitivity (measured using insulin clamp) improved in parallel after 8 weeks of endurance training (r=0.79, P<0.01). We concluded that mitochondrial functions, OXFA and ISI, are not impaired by age but by physical inactivity and are closely correlated.