Muscle Atrophy Classification: The Need for a Pathway-Driven Approach

It is well known that muscles can waste away (atrophy) due to a lack of physical activity. Muscle wasting commonly presents with reduced muscle strength and an impaired ability to perform daily tasks. Several studies have attempted to categorize muscle atrophy into three main subgroups: physiologic, pathologic, and neurogenic atrophy. Physiologic atrophy is caused by the general underuse of skeletal muscle (e.g., bedridden). Pathologic atrophy is characterized as the loss of stimulus to a specific region (e.g., aging). Neurogenic atrophy results from damage to the nerve innervating a muscle (e.g., SMA, GBS). Mechanisms have been elucidated for many of these pathways (e.g., ubiquitin-proteasome system, NF-ΚB, etc.). However, many causes of muscle atrophy (e.g., burns, arthritis, etc.) operate through unelucidated signaling cascades. Therefore, this review highlights the underlying mechanisms of each subtype of muscle atrophy while emphasizing the need for additional research in properly classifying and identifying muscle atrophy.