Antioxidants and aging: NMR-based evidence of improved skeletal muscle perfusion and energetics

Abstract

We sought to examine the potential role of oxidative stress on skeletal muscle function with advancing age. Nuclear magnetic resonance (NMR) was employed to simultaneously assess muscle perfusion (arterial spin labeling) and energetics ((31)P NMR spectroscopy) in the lower leg of young (26 + or - 5 yr, n = 6) and older (70 + or - 5 yr, n = 6) healthy volunteers following the consumption of either placebo (PL) or an oral antioxidant (AO) cocktail (vitamins C and E and alpha-lipoic acid), previously documented to decrease plasma free radical concentration. NMR measurements were made during and after 5 min of moderate intensity (approximately 5 W) plantar flexion exercise. AO administration significantly improved end-exercise perfusion (AO, 50 + or - 5, and PL, 43 + or - 4 ml x 100 g(-1) x min(-1)) and postexercise perfusion area under the curve (AO, 1,286 + or - 236, and PL, 866 + or - 144 ml/100 g) in older subjects, whereas AO administration did not alter hemodynamics in the young group. Concomitantly, muscle oxidative capacity (time constant of phosphocreatine recovery, tau) was improved following AO in the older (AO, 43 + or - 1, and PL, 51 + or - 7 s) but not the young (AO, 54 + or - 5, and PL, 48 + or - 7 s) group. These findings support the concept that oxidative stress may be partially responsible for the age-related decline in skeletal muscle perfusion during physical activity and reveal a muscle metabolic reserve capacity in the elderly that is accessible under conditions of improved perfusion.

Fig. 1.

A: example ¹H image of the lower leg (Ultrafast spin echo imaging, 6 × 6 mm; field of view, 22 × 11 cm; and acquisition matrix, 128 × 36) used for perfusion mapping. Four regions of interest have been highlighted from medial (left side of image) to lateral (right side of image). B: stack plot of ³¹P spectra (−7 to 20 parts/million) with visible changes in the phosphocreatine (PCr) peak (⁻1.5–1.5 parts/million) during plantar flexion exercise.

Fig. 2.

Lower leg perfusion kinetics (top) and PCr resynthesis (bottom) at the end of 5-min plantar flexion exercise in young subjects following consumption of either antioxidant (AO) cocktail (light gray) or placebo (PL; dark gray). AO consumption did not significantly alter perfusion or metabolism in this group. Dashed line indicates the cessation of exercise. Values are means ± SE. AUC, area under the curve; τ, time constant.

Fig. 3.

Lower leg perfusion kinetics (top) and PCr resynthesis (bottom) at the end of 5-min plantar flexion exercise in older subjects following consumption of either AO cocktail (light gray) or PL (dark gray). AO consumption significantly improved both perfusion and metabolism in this cohort. Dashed line indicates the cessation of exercise. Values are means ± SE. *P < 0.05, significantly different than PL.

Fig. 4.

End-exercise P_i-to-PCr ratio (P_i/PCr) in older (black) and young (gray) subjects. Values are means ± SE. *P < 0.05, significantly different than older group.