Short reportWeakness, SR function and stress in gastrocnemius muscles of aged male rats
Introduction
Much attention has been devoted to sarcopenia, the age-related loss of skeletal muscle mass, and its relationship to disability (Janssen et al., 2002, Lauretani et al., 2003). However, accumulating data indicate both that muscle weakness contributes to disability more than loss of muscle size in aged populations (Clark and Manini, 2008), and that age-related loss of muscular force is proportionately greater than the loss of muscle mass (Andersson et al., 2011, Delmonico et al., 2009). This disconnect between force and mass indicates a decline in muscle quality, defined as force production per unit muscle tissue (Russ et al., 2012a).
We have recently reported impaired force production and locomotor performance in aged relative to adult rats, despite minimal changes in muscle mass or myosin heavy chain (MHC) profile (Horner et al., 2011, Russ et al., 2011). We have also observed that aged sarcoplasmic reticulum (SR) exhibits reduced Ca2 +-release function and increased markers of endoplasmic reticulum (ER) stress (Russ et al., 2011, Russ et al., 2012b). SR Ca2 +-release is a critical process in muscle excitation–contraction (E–C) coupling. Disruption at any point in this process can prevent optimal activation of muscle mass and reduce muscle quality. Thus, despite several studies that report no age-related decline in the SR Ca2 +-release channel (ryanodine receptor) (for recent review, c.f. (Russ et al., 2012a)), several investigators have suggested that impairments of E-–C coupling contribute to deficits of muscle quality in aged muscles (Andersson et al., 2011, Russ et al., 2011, Weisleder et al., 2006).
The present study extends our earlier work in these areas in several important ways. Our earlier studies evaluated muscle contractile function in the entire plantar flexor group, making it impossible to determine the optimal length of force production (l0) for any of individual muscles. At least some of the difference in force production observed might therefore have been due to the aged and adult muscles being tested at different points on the length–tension curve. In the present study, we test the isolated medial gastrocnemius. Our previous reports on SR function described muscle homogenates, leaving open the potential that our observations of impaired SR Ca2 +-release were not due to inherent deficits in SR function, but instead the result of cytosolic factors modifying the SR function. Here, we examine SR function specifically in intact SR vesicles. We also measure SR-associated glycogen, as reduced SR-glycogen has been linked to reduced SR Ca2 +-release (Ortenblad et al., 2011), though it has not, to our knowledge, been reported in aging. We further evaluated a number of SR-bound protein markers: glycogen phosphorylase, elevated levels of which have been linked to impaired SR Ca2 +-release (Hirata et al., 2003), as well as Grp78, a classic indicator of ER stress. Because ER stress has been associated with alterations in membrane lipid composition, particularly increases in ceramides (Nikolova-Karakashian and Rozenova, 2010), we also examined the SR content of several proteins associated with membrane metabolism and ceramide production.
Section snippets
Animals & ethical approval
Animal use and all procedures were approved by the Ohio University Institutional Animal Care and Use Committee, and the “Principles of Laboratory Animal Care” (NIH Publication No. 86-23, revised 1985), were followed throughout the study. A total of 10 adult (7–8 months) and 8 aged (24 months), male F344/BN hybrid rats were used in this study. Animals were housed in an environmentally controlled facility (12–12 h light–dark cycle, 22 °C), and had ad libitum access to food and water.
In situ muscle force
Animals were
Animal and muscle mass
There were significant age-related differences in body mass, but not MG muscle mass. As a result the muscle mass:body mass ratio was significantly reduced in the aged rats (Table 1).
In situ muscle force
A significant effect of age and age × frequency interaction was observed for muscle force (Fig. 1A) with all tested frequencies ≥ 50 Hz force being reduced in aged muscles. This was somewhat different than our earlier work on the plantar flexor group, where significant differences occurred only at frequencies ≥ 75 Hz.
Discussion
Our MG force–frequency data were similar to those we have previously reported from the whole plantar flexor muscle group (Horner et al., 2011, Russ et al., 2011). Given the overwhelming proportion of the total plantar flexor mass that is attributable to the gastrocnemii, this is not surprising. However, we found that the age-related decline in muscle quality, though still significant, was not quite as robust as what we found for the entire plantar flexor group. In the present study, we were
Conclusions
Our data indicate that muscle force and SR Ca2 + release decline with age, despite minimal changes in mass or MHC isoform expression. The isolated SR from aged muscle exhibited increases in markers of ER stress and ceramide synthesis, but reduced expression of Parkin—an important protein in targeting organelles for autophagy. These data are consistent with a hypothesis that age-related impairments of the SR, possibly due to altered membrane metabolism and/or impaired autophagy, contribute to
Conflict of interest
The authors have no conflicts of interests.
Acknowledgments
Financial assistance for this project was provided to Dr. Russ by the Ohio University Research Challenge Fund and also a College of Health Sciences and Professions Summer Research Award. Ms. Boyd, Ms. Krause and Ms. Wills were supported by the College of Health Sciences and Professions Graduate Assistantships throughout the project, and Ms. Boyd received a College of Health Sciences and Professions Student Research Grant.
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