Aging-related changes in PGC-1α and muscle-specific kinase (MuSK). (A) Aging-related changes in PGC-1α expression. Data adapted from  (with permission from Oxford University Press), where PGC-1α expression was determined in gastrocnemius muscle of young adult (YA; 8 to 10 months) late middle-aged (LMA; 30 months) and senescent (SEN; 35 months) Fisher 344/Brown Norway F1 hybrids rats. Note the dramatic decrease in muscle PGC-1α expression from adulthood to LMA and its partial recovery from LMA to SEN. (B) Evidence for aging-related decrease in MuSK content at the neuromuscular junction (NMJ). MuSK protein content at the NMJ was determined in situ by immunolabeling plantaris cross-sections from YA (6 months) and SEN (35 months) rats with DAPI (labeling nuclei - blue in merge image), α-bungarotoxin (labeling acetylcholine receptors - green in merge image), and anti-MuSK antibody (kindly provided by Dr. Markus Rüegg; red in merge image) using protocols we previously described [22, 57]. A control slide, for which the incubation with the anti-MuSK antibody was omitted, is presented at the bottom of panel B. White arrows point toward a NMJ having very low MuSK protein content in SEN muscle. (C) Aging-related changes in PGC-1α determined in situ. Cross-sections of the white (glycolytic) gastrocnemius region of one YA and SEN rat were immunolabeled for PGC-1α (green), dystrophin (red) and nuclei (blue) according to methods described in . The anti-PGC-1α antibody was purchased from Millipore (AB3242; Millipore, Billerica, MA, USA). PGC-1α content was quantified by tracing each fiber using ImageJ (images on the right). A control slide, for which incubation with the anti-PGC-1α antibody was omitted, is presented at the bottom. The graph on the right presents PGC-1α content as a function of fiber size. *P <0.05 vs. YA, #P <0.05 vs. small fibers (<1000 μm2). DAPI, 4′,6′-diamidino-2-phénylindole; PGC-1α, peroxisome proliferator-activated receptor gamma coactivator 1-alpha.