Age-related Changes In Markers Of Oxidative Injury In Fast And Slow Muscles Of Male And Female Rats

PURPOSE: To investigate age-related differences in markers of oxidation in fast and slow mammalian muscles. METHODS: This study investigated protein and lipid oxidation, as well as iron accumulation in the extensor digitorum longus (EDL) and Soleus (Sol) muscles of adult (Ad) and aged (Ag, 75% lifespan) male (M) and female (F) F344/BN hybrid rats (n = 7-9/grp). In vivo (grip strength) and ex vivo force generating capacity was determined in the same animals. Muscle tissue was analyzed for levels of protein carbonyls (PC), 4-hydroxynonenal (4HNE) and non-heme iron (NHI). Group comparisons were made via 3-way ANOVA (Age, Sex, Muscle) with muscle as a repeated factor. RESULTS: An effect of muscle was observed only for PC (p = 0.042), which also exhibited interactions with sex and age (p = 0.050, 0.048, respectively). This was due to the fact that PC were lower in the Sol vs. the EDL (37-55%), except in Ag M, where they were elevated (34%). No other main effects or interactions with sex were observed. All 3 oxidation measures showed a significant main effect for an increase with old age in each muscle (4HNE: EDL = 62%, SOL = 40%; NHI: EDL = 300%, SOL = 240%; ;all p ≤ 0.023), except for PC (EDL = 10%, p = 0.678, SOL = 200%, p < 0.001) . Additional correlations between the markers of oxidative injury and indices of force generation showed no significant associations with ex vivo peak force in either muscle, but in vivo grip strength was negatively associated with NHI and PC levels in the SOL (r = -0.433, p = 0.050; r = -0.477, p = 0.018, respectively). Interestingly, 4HNE, but not NHI or PC, was negatively associated with the ratio of indirectly-/directly-stimulated peak force in both the EDL and SOL (r = -0.522, p = 0.038; r = -0.505, p = 0.046, respectively). Both EDL and SOL did exhibit a reduction in this ratio in aged vs. adult animals, suggesting an age-related impairment in peripheral neural activation. Though the difference was comparable in the two muscles similar, it was statistically significant in the SOL (-5.4%, P = 0.038), but not the EDL (-4.6%, P = 0.075). CONCLUSIONS: These findings suggest that different markers of muscle oxidative damage may differentially influence age-related central and peripheral neuromuscular factors in aging muscle function. NIH/NIA R03 AG060143-01A1