Weakness, SR function and stress in gastrocnemius muscles of aged male rats.

Aging is associated with a decline in muscle force that exceeds loss of muscle mass, suggesting that factors other than sarcopenia affect age-related muscle weakness. Here, we investigate in situ muscle force and sarcoplasmic reticulum (SR) properties in gastrocnemius muscles of adult (6-8 months) and aged (24 months) rats. Despite minimal loss of muscle mass, peak tetanic force was significantly reduced (-28%) in aged muscles. Adjusting for differences in muscle cross-sectional area mitigated the age difference (-23%), but it remained significant. The SR calcium release function was also impaired (-17%) with aging, although calcium uptake was not, and SR-associated glycogen increased (+30%) with aging. Western blotting revealed age related increases in Grp78, serinepalmitoyltransferase and neutral sphingomyelinase, suggesting that age increased the stress response and ceramide metabolism in the SR. In contrast Parkin, a protein associated with autophagic signaling, was reduced in the aged SR. These findings are consistent with a hypothesis that age-related impairments of the SR, possibly due to impaired autophagy and/or altered membrane metabolism, contribute to age-related muscle weakness, independent of changes in muscle mass.

"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.

Development of a neuromuscular electrical stimulation protocol for sprint training.

PURPOSE: Sprint training is associated with several beneficial adaptations in skeletal muscle, including an enhancement of sarcoplasmic reticulum (SR) Ca(2+) release. Unfortunately, several patient populations (e.g., the elderly, those with cardiac dysfunction) that might derive great benefit from sprint exercise are unlikely to tolerate it. The purpose of this report was to describe the development of a tolerable neuromuscular electrical stimulation (NMES) protocol that induces skeletal muscle adaptations similar to those observed with sprint training. METHODS: Our NMES protocol was modeled after a published sprint exercise protocol and used a novel electrode configuration and stimulation sequence to provide adequate training stimulus while maintaining subject tolerance. Nine young, healthy subjects (four men) began and completed the training protocol of the knee extensor muscles. RESULTS: All subjects completed the protocol, with ratings of discomfort far less than those reported in studies of traditional NMES. Training induced significant increases in SR Ca(2+) release and citrate synthase activity (~16% and 32%, respectively), but SR Ca(2+) uptake did not change. The percentage of myosin heavy chain IIx isoform was decreased significantly after training. At the whole muscle level, neither central activation nor maximum voluntary isometric contraction force were significantly altered, although isometric force did exhibit a trend toward an increase (~3%, P = 0.055). Surprisingly, the NMES training produced a significant increase in muscle cross-sectional area (~3%, P = 0.04). CONCLUSIONS: It seems that an appropriately designed NMES protocol can mimic many of the benefits of sprint exercise training, with a low overall time commitment and training volume. These findings suggest that NMES has the potential to bring the benefits of sprint exercise to individuals who are unable to tolerate traditional sprint training.