Age-related Changes In Contractile Function Of Mouse Soleus And Edl Muscles

Abstract

PURPOSE: Rodent models are often studied to gain insight into aging in human muscle. However, lifespan is not consistent across rodent species or strains, and muscular impairments may not occur at the same relative age (i.e., % survival). We have previously reported ~25% loss of muscle force in rats in early-stage aging, despite smaller (8-15%) declines in muscle mass. It has been suggested that mice, despite shorter lifespans, exhibit less sarcopenia than rats. The goal of the present study was to study the contractile responses of two muscles in aging mice of the same absolute age (24 months), but greater relative age (75% survival, ~ 75 yo in humans), as the rats we have previously studied. METHODS: Ex vivo contractility was studied in the soleus (SOL) and extensor digitorum longus (EDL) muscles of adult (n = 6, 12 mo.) and aged (n = 7, 24 mo.) male, C57Bl/6 mice. All muscles underwent force-frequency relation (FFR) testing and fatigue. Force, muscle quality (force/cross-sectional area (CSA)) and contractile properties for twitch and peak tetanic stimulation were determined for each muscle. RESULTS: Overall analysis of the FFR revealed a significant main effect of muscle and age x frequency and age x frequency x muscle interactions (all P < 0.001). Muscle mass did not differ with age, although there was a trend toward an effect in SOL (P = 0.062). Age significantly (P = 0.035) reduced twitch force in the EDL, but not the SOL, and maximum tetanic force showed no effect of age in either muscle. Twitch contractile properties did not differ with age or muscle. However tetanic rates of force development and relaxation in the EDL were reduced with age (P = 0.065 & 0.098, respectively), differences which became significant when normalized to force (P = 0.018 & 0.035, respectively). No differences in muscle fatigue were found in either muscle. CONCLUSIONS: Relative to aging rats, aging mice exhibit modest changes in muscle mass and force in both the EDL and SOL. Changes in force appear largely determined by changes in mass. Since many studies of human aging indicate that loss of force exceeds loss of strength, these data suggest that mice may not fully recapitulate all aspects of aging human muscle. Future studies should make efforts to examine muscles other than the EDL and SOL to determine if other muscles more closely model aging human muscle.