A proteomics‐based approach to changes in skeletal muscle gene expression with age‐related sarcopenia

The purpose of this study was to identify proteins that are differentially expressed in sarcopenic rat skeletal muscle. Gastrocnemius muscle was obtained from 18 and 27 mos. old Harlan Sprague Dawley rats (n=3). These ages were chosen based on the 50% reduction in muscle mass and maximum force that were observed over this period. Muscle homogenates were prepared, run on 2‐D gels (n=3‐4 gels per muscle) and optimum gels chosen for overlay and identification of altered proteins. Twenty‐six proteins, some with multiple isoforms, were differentially regulated with 16 being down‐regulated and 10 being up‐regulated in 27 vs. 18 mos. gastrocnemius muscle. The altered proteome included changes in: i) contractile proteins reflecting a decrease in fast muscle‐specific and an increase in slow muscle‐specific proteins; ii) enzymes of metabolic pathway reflecting an increase in PCr metabolism but decreases in glycolytic and oxidative metabolism; and iii) increased anti‐oxidant enzymes reflecting a compensatory response to oxidative stress. These data support previous reports of a loss of fast twitch fibres and demonstrate concomitant decreases in oxidative and glycolytic capacities. These data suggest that altered muscle fibre type and metabolic rate along with increased cellular oxidative stress contribute to the age‐related decrease in muscle function.