Possibility of small-molecule-based pharmacotherapy for sarcopenia

Abstract

Muscle mass and strength decline with age. When severe, the loss is called sarcopenia. Sarcopenia is drawing attention worldwide, especially in highly aged societies, as a disease that should be treated. At present, we have limited tools to combat sarcopenia (e.g. resistance training and nutritional intervention), but accumulating knowledge of the molecular and cellular mechanisms of sarcopenia is accelerating the development of pharmacological therapies for sarcopenia. Because sarcopenia is a complicated pathological condition caused and modified by many aging-related factors, such as inactivity, loss of motor neurons, poor nutrition, decline of anabolic hormones, chronic inflammation, oxidative stress, impaired stem cell function, and comorbidity, the proposed target molecules or pathways for pharmacological intervention are diverse. Here we review recent progress in drug development with emphasis on small-molecule compound-based therapies and review the literature to identify new therapeutic targets to prevent, delay, or reverse sarcopenia.

Targeting Inflammation and Downstream Protein Metabolism in Sarcopenia: A Brief Up-Dated Description of Concurrent Exercise and Leucine-Based Multimodal Intervention

“…Sarcopenia is a multifactorial syndrome, and given its multifaceted pathophysiology, a multimodal approach to sarcopenia management should be advocated. Over the past 30 years, the single intervention specifically aimed at increasing food intake, attenuating inflammation, or ameliorating protein balance disorders has provided limited results in the management of sarcopenia; research on the effectiveness of anti-inflammatory based single-mode treatment appears to be limited (Landi et al, 2013 ); high-dose hormone replacement therapy results are ambiguous and controversial because of the potential side-effects (Giannoulis et al, 2012 ); and no pharmaceutical drugs have been approved as potent treatments for sarcopenia (Watanabe and Miyagoe-Suzuki, 2015 ).…”