p62/SQSTM1 but not LC3 is accumulated in sarcopenic muscle of mice

Abstract

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.

Growth hormone secretagogues hexarelin and JMV2894 protect skeletal muscle from mitochondrial damages in a rat model of cisplatin-induced cachexia

“…Moreover it has been shown that defective autophagy contributes to the pathogenesis of different forms of muscular distrophies associated with accumulation of altered organelles into myofibers or abnormal degradation of myofibers components 57 . Also ageing is accompanied by autophagic defects as shown by studies performed in human and mice skeletal muscles 58,59 . Overall these evidences support the concept that cisplatin treatment recapitulates the main features of cancer-induced cachexia, and thus making the cisplatin-treated rats an useful and valuable model to investigate the molecular bases of this syndrome.…”

Involvement of AMPK in regulating slow-twitch muscle atrophy during hindlimb unloading in mice

“…Accumulation of p62 generally indicates an impairment of autophagy flux (46), but p62 hyperexpression was also observed in cancer cachexia-induced skeletal muscle atrophy despite the autophagy induction (56). In addition, a recent study reported the accumulation of p62 in atrophic muscle of aged mice (60). Although our findings indicate that AMPK modulates the expression of autophagy-related proteins during unloading-induced muscle atrophy, we cannot ascertain whether AMPK-mediated autophagy regulation is associated with the progress of muscle atrophy in response to hindlimb unloading.…”

Skeletal Muscle Dysfunction in Critical Illness

“…The elevated levels of LC3 and Beclin-1 mRNA expression were also reported in skeletal muscle after 3 or 7 days of denervation [64]. Under such conditions of inactivity, such as the late phase, autophagy seems to modulate muscle atrophy accompanying inactivity [96].…”