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Age‐Related Perturbations in the Sarcolemmal Environment are Attenuated by Lifelong Caloric Restriction and Voluntary Wheel Running

Sarcopenia is the age‐related reduction in skeletal muscle mass and strength. Previously we observed that lifelong mild caloric restriction (CR) and wheel running (WR) attenuated sarcopenia, in part by reducing the age‐induced disruptions of the sarcolemmal dystrophin‐glycoprotein complex (DGC) proteins. The purpose of this study was to determine if mild (8%) CR and lifelong CR + voluntary WR could maintain a phenotypically young sarcolemmal environment in plantaris muscle fibers. Fischer 344 rats were assigned into four groups: 6‐month‐old sedentary ad libitum (YAL), 24‐month‐old sedentary ad libitum group (OAL), 8% caloric restriction from 11 months – 24 months (OCR), and 8% CR plus voluntary wheel running from 11 months – 24 months (OCRWR). We observed significant age‐related increases in key membrane repair proteins (MG53, p < 0.0001; dysferlin, p < 0.0001; annexin A6, p < 0.0001; and annexin A2, p = 0.004) in the OAL plantaris. Lifelong mild CR and CRWR interventions were effective at maintaining membrane repair proteins near YAL levels. Consistent with a perturbed sarcolemmal environment, we also found reduced protein content of NADPH oxidase isoform 2 (Nox2) subunits (p67phox, p = 0.03; p47phox, p = 0.01; and gp91phox, p = 0.096). Lifelong CR and CRWR protected against the age‐related reduction in gp91phox, p47phox, and p67phox proteins. Nox2 subunit abundance in OCR and OCRWR were not significantly different than YAL, while p67phox was significantly higher in OCR than YAL (p = 0.03). Novel data presented here are consistent with the hypothesis that lifelong CR and WR mitigate sarcopenia, in part, by ameliorating age‐induced alterations in the myofiber membrane environment.