AimWe investigated the pathway of autophagy signaling linked to sarcopenia of mice.MethodsYoung adult (3‐month) and aged (24‐ month) C57BL/6J mice were used. Using real‐time PCR, Western blotting, and immunohistochemical microscopy, we evaluated the amounts of p62/SQSTM1, LC3, and Beclin‐1 in the quadriceps muscle change with aging in mice.ResultsMarked fiber atrophy (30%) and many fibers with central nuclei were observed in the aged mice. Western blotting using homogenate of the cytosolic fraction clearly showed that the amounts of p62/SQSTM1 and Beclin‐1 proteins were significantly increased in the aged skeletal muscle. The amounts of these proteins in both nuclear and membrane fractions did not change significantly with age. Immunofluorescence labeling indicated that aged mice more frequently possessed p62/SQSTM1‐positive fibers in the cytosol in quadriceps muscle than young ones (aged: 14% vs. young: 1%). In aged muscle, p62/SQSTM1‐positive fibers were significantly smaller than the surrounding p62/SQSTM1‐negative fibers. Aging did not elicit significant changes in the mRNA levels of p62/SQSTM1 and Beclin‐1, but decreased LC3 mRNA level. In aged muscle, the location of p62/SQSTM1 immunoreactivity was similar to that of Beclin‐1 protein, but not LC3.ConclusionSarcopenia in mice appears to include a marked defect of autophagy signaling.
The isoflavone aglycone (AglyMax) at a 0.6% significantly would modulate muscle atrophy after denervation in mice, probably due to the decrease in apoptosis-dependent signaling.
Decrease in activity stress induces skeletal muscle atrophy. A previous study showed that treatment with resveratrol inhibits muscular atrophy in mdx mice, a model of DMD. However, almost all studies using resveratrol supplementation have only looked at adaptive changes in the muscle weight. The present study was designed to elucidate whether the resveratrol-inducing attenuation of skeletal muscle actually reflects the adaptation of muscle fibers themselves, based on the modulation of atrogin-1- or p62-dependent signaling. Mice were fed either a normal diet or 0.5% resveratrol diet. One week later, the right sciatic nerve was cut. The wet weight, mean fiber area, and amount of atrogin-1 and p62 proteins were examined in the gastrocnemius muscle at 14 days after denervation. The 0.5% resveratrol diet significantly prevented denervation-induced decreases in both the muscle weight and fiber atrophy. In addition, dietary resveratrol suppressed the denervation-induced atrogin-1 and p62 immunoreactivity. In contrast, 0.5% resveratrol supplementation did not significantly modulate the total protein amount of atrogin-1 or p62 in the denervated muscle of mice. Resveratrol supplementation significantly prevents muscle atrophy after denervation in mice, possibly due to the decrease in atrogin-1 and p62-dependent signaling.
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