Differential cell death regulation between adult-unloaded and aged rat soleus muscle.
Sarcopenia is characterized by increased regenerating myofibres and decreased myofibre size. Sarcopenia progression might be partially regulated by ageing-related signals associated with necrotic fibre disruption and nuclear apoptosis. This study sought to identify ageing-related signals in aged atrophying skeletal muscle by comparison with unloaded muscle atrophy in adults. Adult (6-month) and old (32-month) rats were used. Some adult rats were subjected to 2 weeks of hindlimb unloading (6-month-HU). Histological analysis found that regenerating fibres increased by about 30-fold only in 32-month aged soleus muscle compared with 6-month rats. The number of apoptotic DNA fragmented nuclei was increased by 3.9-fold in 6-month-HU and 2.8-fold in 32-month rats. Cleaved caspase-3 was observed at high levels on basal membranes and in nuclei in 32-month rats. By Western blot analysis additional ageing-related signals could be identified since (1) phosphorylated Bcl-2 content was increased in both cytosolic and mitochondrial fractions; (2) ER stress signal proteins caspase-12, CHOP/GADD153, and GRP78 were increased; and (3) stress-inducible chaperone HSP70 was decreased in soleus muscle from 32-month but not changed in 6-month-HU rats. We conclude that activation of ageing-related signals may mediate necrotic myofibre disruption and nuclear apoptosis induction that contribute to progression of sarcopenia.
Faculty of Sport Sciences, Waseda University, 2-579-15 Mikajima, Tokorozawa, Saitama 359-1192, Japan. ogata@aoni.waseda.jp
Tomonori
T
Ogata
Shuichi
S
Machida
Yasuharu
Y
Oishi
Mitsuru
M
Higuchi
Isao
I
Muraoka
D000367:Age Factors; D000375:Aging / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D017209:Apoptosis; D053148:Caspase 3 / Q000096:biosynthesis; D002463:Cell Membrane Permeability; D004721:Endoplasmic Reticulum / Q000378:metabolism; D008297:Male; D008931:Mitochondria, Muscle / Q000378:metabolism*; D051336:Mitochondrial Membranes / Q000378:metabolism*; D018832:Molecular Chaperones / Q000378:metabolism; D018482:Muscle, Skeletal / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D009133:Muscular Atrophy / Q000201:enzymology / Q000473:pathology*; D009336:Necrosis; D051381:Rats; D011914:Rats, Inbred BN; D011916:Rats, Inbred F344
D018832:Molecular Chaperones; D053148:Caspase 3