G.P.202: Characterization of skeletal muscle and heart during aging in rats, and response to formoterol, a selective β2 adrenoceptor agonist, in aged rats

Abstract

Loss of skeletal muscle function and mass occurs during aging as well as under various disease conditions, such as cancer, COPD, liver disease, and congestive heart failure. Despite the high prevalence of such conditions, no effective treatment for muscle wasting diseases exists. In particular, sarcopenia, under the concept of frailty frequently observed in elderly people, is a geriatric syndrome defined by an excessive reduction in muscle mass and a concurrent decline in physical function, leading to mobility limitations, reduced quality of life, increased risk of falls, fractures and hospitalizations, and ultimately loss of independence. Selective β2 adrenoceptor agonists elicit skeletal muscle hypertrophy associated with increased force producing capacity. Several studies have reported efficacy of β2 adrenoceptor agonists in improving muscle wasting in many animal species and humans. Here, skeletal muscle and heart in aged rats were characterized with regard to mass, function and gene expression changes. Progressive loss of mass and force production capacity in skeletal muscle was observed; in contrast cardiac mass was increased and its function was decreased. In skeletal muscles, these phenotypic changes were associated with dramatic changes in genes known to be involved in atrophy, differentiation and in particular neuromuscular junction. In the heart, gene expression changes indicated pathological remodeling including up-regulation of fetal gene markers. Furthermore, the effect of formoterol on skeletal muscle and heart of aged sarcopenic rats was evaluated. The treatment spared the age-related loss of skeletal muscle mass and force production capacity in rats, while increasing heart weight. Hence, although β2 adrenoceptor agonists might be a potential therapeutic option for treating age-related loss of skeletal muscle, development of skeletal muscle selective agents is awaited since any detrimental cardiac effects may not be tolerated in elderly population.