"SR stress" in mixed hindlimb muscles of aging male rats

Impaired sarcoplasmic reticulum (SR) function has been associated with reduced muscle force generation and locomotor function in aging animals. This study was conducted to determine the extent to which aging increased SR stress markers in male rats, and the extent to which volitional exercise affected them. We harvested medial gastrocnemius muscles from F344/BN rats that were adult (8 months; n = 8), aging (24 months; n = 8) and that aged with wheel access for 16 months (24 months; n = 4). SR calcium handling assays and immunoblotting (Caspase 12, dysferlin and LC3) were performed on crude homogenates and SR-enriched microsomal fractions. Aging was associated with increased Caspase 12 and SR dysferlin, as well as a reduced LC3II/I ratio and impaired calcium release. Despite further increases in Caspase 12, voluntary wheel running partially restored SR calcium release and dysferlin toward younger levels. Of note, the LC3II/I was also partially restored in the voluntary wheel running group, suggesting increased autophagy. These results suggest that impaired SR function with aging is associated with age-related increases in SR stress, possibly related to reduced autophagy. Long-term volitional exercise improved SR function and markers of autophagy, despite increased Caspase 12, suggesting that running contributed a beneficial stress that differed from the "distress" of sedentary aging.