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1 Department of Geriatrics, University of Arkansas for Medical Sciences, Little Rock, AR, USA
2 Department of Geriatrics, University of Arkansas for Medical Sciences, Little Rock, AR, USA; Department of Physiology and Biophysics, University of Arkansas for Medical Sciences, Little Rock, AR, USA; Central Arkansas Veterans Health Care System, Little Rock, AR, USA
3 Department of Geriatrics, University of Arkansas for Medical Sciences, Little Rock, AR, USA; Department of Physiology and Biophysics, University of Arkansas for Medical Sciences, Little Rock, AR, USA
* To whom correspondence should be addressed. E-mail: dupontesthere{at}uams.edu.
Muscle mass is decreased with advancing age likely due to altered regulation of muscle fiber size. This study was designed to investigate cellular mechanisms contributing to this process. Analysis of male F344/BN rats at 6, 20 and 32 months of age demonstrated that even though significant atrophy had occurred in soleus muscle by old age, myofiber nuclear number did not change, resulting in a decreased myonuclear domain. Also, the number of centrally located nuclei was significantly elevated in soleus muscle of 32 month-old rats, correlating with an increase in gene expression of MyoD and myogenin. Whereas total 5'-Bromo-2' deoxyuridine (BrdU) positive nuclei were decreased at older ages, BrdU positive myofiber nuclei were increased. These results suggest that with age, loss of muscle mass is accompanied by increased myofiber nuclear density that involves fusion of proliferative satellite cells, resembling ongoing regeneration. Interestingly, centrally located myofiber nuclei were not BrdU labeled. Rats were subjected to hind limb suspension (HS) for 7 or 14 days and intermittent reloading during HS for one hour each day (IR) to investigate how aging affects the response of soleus muscle to disuse and an atrophy-reducing intervention. After 14 days of HS soleus muscle size was decreased to a similar extent at all three ages. However, myofiber nuclear number and the total number of BrdU positive nuclei decreased with HS only in the young rats. IR was associated with an attenuation of atrophy in soleus muscles of 6 and 20, but not 32 month-old rats. Further, IR was associated with an increase in BrdU positive myofiber nuclei only in young rats. These data indicate that altered satellite cell function with age contributes to the impaired response of soleus muscle to an intervention that attenuates muscle atrophy in young animals during imposed disuse.
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