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.