Emerging molecular mediators and targets for age-related skeletal muscle atrophy

Abstract

The age-associated decline in muscle mass has become synonymous with physical frailty among the elderly due to its major contribution in reduced muscle function. Alterations in protein and redox homeostasis along with chronic inflammation, denervation, and hormonal dysregulation are all hallmarks of muscle wasting and lead to clinical sarcopenia in older adults. Reduction in skeletal muscle mass has been observed and reported in the scientific literature for nearly 2 centuries; however, identification and careful examination of molecular mediators of age-related muscle atrophy have only been possible for roughly 3 decades. Here we review molecular targets of recent interest in age-related muscle atrophy and briefly discuss emerging small molecule therapeutic treatments for muscle wasting in sarcopenic susceptible populations.

Figure 1.

Flow chart of sarcopenia clinical trial studies since October 2019. Data received from clinicaltrials.gov. Roughly three quarters of clinical trials have an interventional approach to investigate treatments for sarcopenia. The interventional approaches to retain lean body mass in older adults have been focused more on lifestyle changes (dietary, exercise) and less on patented technologies (drugs, devices).

Figure 2.

Timeline of interventional clinical trial sarcopenia studies. Sarcopenia studies have gradually increased within the first decade of interventional trials and have abruptly grown within the last decade. Although, production of interventional studies from both the industry and institutions have progressively increased in the past couple decades, drug interventions have remained stable even after the classification of sarcopenia as a disease state in 2016.