Muscle atrophy is not always sarcopenia.

In his closing comments to a scientific congress in 1989, Dr. Irwin Rosenberg suggested that one way to bring greater attention to the issue of the decline in muscle mass with aging was to give it a Greek name (26). Although two terms were suggested (“sarcomalacia” being the other one), “sarcopenia” was the term adopted by the field. A PubMed search for sarcopenia as of this writing yielded more than 1,300 hits, demonstrating its widespread acceptance. Although the term sarcopenia has helped focus attention on this problem of aging, unfortunately in recent years the term has increasingly come to be synonymous with its operational definitions, which use severity of muscle atrophy to define the presence of sarcopenia (e.g., one or two standard deviations less than the muscle mass of a healthy young adult population) (4, 14). As a result, the term sarcopenia is appearing in other clinical literature in which muscle atrophy is present but aging per se is not the cause. Examples of this include the use of the term sarcopenia to describe muscle mass decline due to cirrhosis (20), HIV infection (9), overiectomy (12), and cancer (8). Thus, despite its origins in reference to the muscle atrophy occurring with aging, a growing number of other clinical disciplines now uses the term to define a level of muscle atrophy regardless of the age of the individual. Perhaps the biggest concern for this development is that the consideration of whether aging muscle atrophy may be the result of processes distinct from other forms of muscle atrophy (e.g., that resulting from disuse or cancer) is fading into oblivion in the clinical literature. A clearly unwanted outcome of this is that development of effective treatments for sarcopenia, and other forms of muscle atrophy not associated with aging per se, will be hampered by a false impression that all muscle atrophy is mediated by the same processes. For example, although both denervation atrophy and disuse atrophy are associated with activation of the proteolytic machinery (17), targeted inhibition of proteolysis would have little benefit for a denervated myofiber, whereas this might be very beneficial for a myofiber atrophied only by disuse. Thus, without appropriate biomarkers that are specific to sarcopenia, confusion rather than clarity will result. If we continue down this road, we face the real risk of having the term sarcopenia become permanently separated from its roots in aging, which would undermine the very reason Dr. Rosenberg coined the term in the first place—to raise awareness of this as a problem of aging so that appropriate treatments could be sought. The following Viewpoint article uses the histopathology of aging muscle to make the case that sarcopenia of aging is likely distinct from several other clinical causes of muscle atrophy, including some that are now using the term sarcopenia. As will be shown, many of the morphological features of sarcopenia resemble features seen in muscle that has been impacted by sporadic denervation, such as that seen in neurological disorders like amyotrophic lateral sclerosis (7). Due to space constraints, we will only consider how the histopathology of aging muscle compares with cancer cachexia. However, many of the points made here to distinguish sarcopenia from cancer cachexia should also be considered in other clinical conditions associated with muscle atrophy.