Differential cell death regulation between adult-unloaded and aged rat soleus muscle

Tomonori Ogata, Shuichi Machida, Yasuharu Oishi, Mitsuru Higuchi, Isao Muraoka

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)328-336
Number of pages9
JournalMechanisms of Ageing and Development
Volume130
Issue number5
DOIs
Publication statusPublished - 2009 May

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Skeletal Muscle
Cell Death
Sarcopenia
Caspase 12
Apoptosis
Hindlimb Suspension
Muscular Atrophy
Heat-Shock Proteins
Caspase 3
Western Blotting
Membranes
DNA

Keywords

  • Caspase-3
  • ER stress
  • Mitochondrial membrane permeability
  • Molecular chaperone
  • Sarcopenia

ASJC Scopus subject areas

  • Ageing
  • Developmental Biology

Cite this

Differential cell death regulation between adult-unloaded and aged rat soleus muscle. / Ogata, Tomonori; Machida, Shuichi; Oishi, Yasuharu; Higuchi, Mitsuru; Muraoka, Isao.

In: Mechanisms of Ageing and Development, Vol. 130, No. 5, 05.2009, p. 328-336.

Research output: Contribution to journalArticle

Ogata, Tomonori ; Machida, Shuichi ; Oishi, Yasuharu ; Higuchi, Mitsuru ; Muraoka, Isao. / Differential cell death regulation between adult-unloaded and aged rat soleus muscle. In: Mechanisms of Ageing and Development. 2009 ; Vol. 130, No. 5. pp. 328-336.
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