Sedentary aging increases resting and exercise-induced intramuscular free radical formation

Abstract

Mitochondrial free radical formation has been implicated as a potential mechanism underlying degenerative senescence, although human data are lacking. Therefore, the present study was designed to examine if resting and exercise-induced intramuscular free radical-mediated lipid peroxidation is indeed increased across the spectrum of sedentary aging. Biopsies were obtained from the vastus lateralis in six young (26 + or - 6 yr) and six aged (71 + or - 6 yr) sedentary males at rest and after maximal knee extensor exercise. Aged tissue exhibited greater (P < 0.05 vs. the young group) electron paramagnetic resonance signal intensity of the mitochondrial ubisemiquinone radical both at rest (+138 + or - 62%) and during exercise (+143 + or - 40%), and this was further complemented by a greater increase in alpha-phenyl-tert-butylnitrone adducts identified as a combination of lipid-derived alkoxyl-alkyl radicals (+295 + or - 96% and +298 + or - 120%). Lipid hydroperoxides were also elevated at rest (0.190 + or - 0.169 vs. 0.148 + or - 0.071 nmol/mg total protein) and during exercise (0.567 + or - 0.259 vs. 0.320 + or - 0.263 nmol/mg total protein) despite a more marked depletion of ascorbate and uptake of alpha/beta-carotene, retinol, and lycopene (P < 0.05 vs. the young group). The impact of senescence was especially apparent when oxidative stress biomarkers were expressed relative to the age-related decline in mitochondrial volume density and absolute power output at maximal exercise. In conclusion, these findings confirm that intramuscular free radical-mediated lipid peroxidation is elevated at rest and during acute exercise in aged humans.

Fig. 1.

A: changes in the electron paramagnetic resonance spectral intensity of the residual ascorbate free radical (A^·−). Typical spectra and corresponding masses are also shown for a single young and aged subject. AU, arbitrary units. B: inverse relationship (pooled data) observed between the exercise-induced changes (Δ: exercise minus rest value) in the normalized intramuscular concentration of ascorbate and α-tocopherol. TP, total protein.

Fig. 2.

A: changes in the spectral intensity of the g = 2.004 signal expressed relative to the TP concentration with typical spectra and corresponding masses. B: data were further normalized for mitochondrial volume density (%_MIT). C: exercise values were further corrected for (single-leg) maximal absolute power output (in W). UQ^·−, ubisemiquinone radical. †Significantly different (P < 0.05) between groups.

Fig. 3.

A: changes in the spectral intensity of α-phenyl-tert-butylnitrone adducts identified as a combination of lipid-derived alkoxyl-alkyl radicals (LO^·-LC^·) expressed relative to tissue mass. B and C: data after further normalization. *Significantly different (P < 0.05) between conditions for a given group; †significantly different (P < 0.05) between groups for a given condition.

Fig. 4.

A: changes in the concentration of lipid hydroperoxides (LOOH) expressed relative to TP concentration. B and C: data after further normalization. †Significantly different (P < 0.05) between groups for a given condition.