Aging influences cellular and molecular responses of apoptosis to skeletal muscle unloading

Parco M. Siu, Emidio E. Pistilli, David C. Butler, Stephen Alway

Research output: Contribution to journalArticle

114 Citations (Scopus)

Abstract

The influence of aging on skeletal myocyte apoptosis is not well understood. In this study we examined apoptosis and apoptotic regulatory factor responses to muscle atrophy induced via limb unloading following loading-induced hypertrophy. Muscle hypertrophy was induced by attaching a weight to one wing of young and aged Japanese quails for 14 days. Removing the weight for 7 or 14 days after the initial 14 days of loading induced muscle atrophy. The contralateral wing served as the intra-animal control. A time-released bromodeoxyuridine (BrdU) pellet was implanted subcutaneously with wing weighting to identify activated satellite cells/ muscle precursor cells throughout the experimental period. Bcl-2 mRNA and protein levels decreased after 7 days of unloading, but they were unchanged after 14 days of unloading in young muscles. Bcl-2 protein level but not mRNA level decreased after 7 days of unloading in muscles of aged birds. Seven days of unloading increased the mRNA level of Bax in muscles from both young and aged birds. Fourteen days of unloading increased mRNA and protein levels of Bcl-2, decreased protein levels of Bax, and decreased nuclear apoptosis-inducing factor (AIF) protein level in muscles of aged birds. BrdU-positive nuclei were found in all unloaded muscles from both age groups, but the number of BrdU-positive nuclei relative to the total nuclei decreased after 14 days of unloading compared with 7 days of unloading. The TdT-mediated dUTP nick end labeling (TUNEL) index was higher after 7 days of unloading in both young and aged muscles and after 14 days of unloading in aged muscles. Immunofluorescent staining revealed that almost all of the TUNEL-positive nuclei were also BrdU immunopositive, suggesting that activated satellite cell nuclei (both fused and nonfused) underwent nuclear apoptosis during unloading. There were significant correlations among levels of Bcl-2, Bax, and AIF and TUNEL index. Our data are consistent with the hypothesis that apoptosis regulates, at least in part, unloading-induced muscle atrophy and loss of activated satellite cell nuclei in previously loaded muscles. Moreover, these data suggest that aging influences the apoptotic responses to prolonged unloading following hypertrophy in skeletal myocytes.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Cell Physiology
Volume288
Issue number2 57-2
DOIs
StatePublished - Feb 1 2005
Externally publishedYes

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Hindlimb Suspension
Cell Aging
Skeletal Muscle
Apoptosis
Muscles
Bromodeoxyuridine
Muscular Atrophy
Apoptosis Inducing Factor
Hypertrophy
Birds
Messenger RNA
Skeletal Muscle Fibers
Cell Nucleus
Weights and Measures
bcl-2-Associated X Protein
Coturnix
Apoptosis Regulatory Proteins
Proteins
Myoblasts
Nuclear Proteins

All Science Journal Classification (ASJC) codes

  • Physiology
  • Cell Biology

Cite this

Aging influences cellular and molecular responses of apoptosis to skeletal muscle unloading. / Siu, Parco M.; Pistilli, Emidio E.; Butler, David C.; Alway, Stephen.

In: American Journal of Physiology - Cell Physiology, Vol. 288, No. 2 57-2, 01.02.2005.

Research output: Contribution to journalArticle

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