A STUDY OF THE EFFECT OF AGING ON SOME SKELETAL MUSCLE PARAMETERS AND THE POSSIBLE ROLE OF A BETA-2-AGONIST
Zainab Abd Elwahab and Soha Ali El-Moursy*
Departments of Physiology and *Clinical Pharmacology, Faculty of Medicine, Cairo University
Background: Aging is a normal physiological process associated with progressive loss of skeletal muscle mass and subsequent decline in muscle strength. Synthetic ?eta-2-adrenoceptor agonists were initially developed to facilitate broncho-dilation to relieve asthma. It was suggested that at doses higher than those used therapeutically, ?eta2 agonists were capable of eliciting significant skeletal muscle hypertrophy. Sarcoplasmic reticulum Ca2+ ATPase (SERCA) is one of the principal regulators of Ca2+ homeostasis in the skeletal muscle cells. However, the effects of aging and ?eta-2-agonists on the kinetic properties of the SERCA are not clear. The purpose of this work was to study the effect of the physiological process associated with aging on skeletal muscle and to clarify the underlying mechanism of ?eta2 agonsit in this regard.
Methods: Forty male albino rats were used in this study, twenty of which were adults (12 months of age) and the rest were old (24 months). Each group was divided into two groups: a control and a ?eta2 agonist (formoterol) treated group (n = 10 in each). Each animal was weighed and formoterol was injected intraperitoneally (IP) in a dose of 1ug/kg/day for 4 weeks. Animals were re-weighed at and the end of the 4-week period, and then were anaesthetized by inhalation of ether and the following parameters were recorded from the soleus muscle: its weight, Twitch Tension (TT) time to peak tension (TPT), and half relaxation time (1/2 RT). Measurement of SERCA1 protein level was done from soleus muscle tissue samples.
Results: It was found that the final body weight, soleus muscle weight, (TT), (TPT), (1/2 RT), and SERCA1 protein levels were significantly lower in old controls as compared to adult controls; formoterol treated groups showed significantly higher values (p < 0.05) in all of the previous parameters when compared with their age matching controls.
Conclusion: Treating old rats with the beta-2-agonist, formoterol at a daily dose of 1 μg/kg could ameliorate the age associated loss of skeletal muscle mass, improve their force of contraction and reverse the prolongation in contraction and relaxation time. These effects were associated with an increase in SERCA1 protein level which is thus a possible mechanism of action. The possible use of formoterol as a therapeutic intervention for muscle wasting is further supported by the fact that it is currently in use for the prevention and treatment of asthma. Formoterol can be used in micromolar doses to avoid any undesirable effects.