Review Volume 3, Issue 8 pp 702—715

Inducible nitric oxide synthase (iNOS) in muscle wasting syndrome, sarcopenia, and cachexia


Figure 2. Underlying mechanisms involved in muscle wasting diseases. Despite the fact that both diseases result in muscle wasting, the underlying causes of sarcopenia (blue) and cachexia (orange) are distinct. Sarcopenia arises from a multitude of factors, including [1] decreased amino acid intake, [2] diminished physical activity, [3] loss of motor neurons with age, and [4] a decline in anabolic stimulating hormones. Cachexia, in contrast, results from the physiological changes that occur during the progression of other chronic inflammatory illnesses. In cancer, the REE (Resting Energy Expenditure) is known to increase, pushing the overall energy state towards a negative energy balance. This effect is further exacerbated (dashed arrow) by anorexia, which, although not a direct cause of cachectic muscle loss, often accompanies cachexia and contributes towards the overall negative energy balance. Finally, several host humoral factors, such as glucocorticoids and angiotensin II, are known to induce muscle wasting, affecting the overall metabolic state by either by augmenting catabolism, decreasing anabolism, or both. Furthermore, the tumor factor PIF (Proteolysis Inducing Factor) has also been implicated in murine models of cancer cachexia, though its role in human cachexia has yet to be confirmed. In addition to the above factors, inflammatory cytokines are believed to play a key role in the pathology of both sarcopenia and cachexia. As a uniquely common cause of both diseased states, inflammatory cytokines represent an enticing target for the development of drug therapies.