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Differential regulation of apoptosis in slow and fast twitch muscles of aged female F344BN rats

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Abstract

Age-related muscle atrophy is characterized by decreases in muscle mass and is thought be mediated, at least in part, by increases in myocyte apoptosis. Recent data has demonstrated that the degree of muscle loss with aging may differ between males and females while other work has suggested that apoptosis as indicated by DNA fragmentation may be regulated differently in fast- and slow-twitch muscles. Herein, we investigate how aging affects the regulation of muscle apoptosis in the fast-twitch extensor digitorum longus (EDL) and slow-twitch soleus muscles of young (6-month), aged (26-month), and very aged (30-month) female Fischer 344/NNiaHSD × Brown Norway/BiNia (F344BN) rats. Tissue sections were stained with hydroethidium for ROS and protein extract was subjected to immunoblotting for assessing apoptotic markers. Our data suggest that decreases in muscle mass were associated with increased DNA fragmentation (TUNEL positive) and increases in reactive oxygen species (ROS) as determined by hydroethidium staining in both the EDL and soleus. Similar to our previous work using aged male animals, we observed that the time course and magnitude of changes in Bax, Bcl-2, caspase-3, caspase-9, and cleavage of α-fodrin protein were regulated differently between muscles. These data suggest that aging in the female F344BN rat is associated with decreases in muscle mass, elevations in ROS level, increased muscle cell DNA fragmentation, and alterations in cell membrane integrity and that apoptotic mechanisms may differ between fiber types.

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Acknowledgments

This study was supported by DOE funding no. DE-SC0005162 to E.R.B.

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Authors and Affiliations

  1. Center for Diagnostic Nanosystems, Marshall University, Room 241D, Robert C. Byrd Biotechnology Science Center Building, 1700 3rd Ave., Huntington, WV, 25755-1090, USA

    Kevin M. Rice, Nandini D. P. K. Manne, Murali K. Gadde, Satyanarayana Paturi, Ravikumar Arvapalli & Eric Blough

  2. Department of Pharmacology, Physiology and Toxicology, Joan C. Edwards School of Medicine, Huntington, WV, USA

    Nandini D. P. K. Manne & Eric Blough

  3. Department of Pharmacology, Physiology and Toxicology, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV, USA

    Eric Blough

  4. Department of Pharmaceutical Sciences and Research, Marshall University, Huntington, WV, USA

    Eric Blough

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  1. Kevin M. Rice
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Correspondence to Kevin M. Rice.

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Rice, K.M., Manne, N.D.P.K., Gadde, M.K. et al. Differential regulation of apoptosis in slow and fast twitch muscles of aged female F344BN rats. AGE 37, 30 (2015). https://doi.org/10.1007/s11357-015-9767-z

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  • DOI: https://doi.org/10.1007/s11357-015-9767-z

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