Michelangelo, the Sistine Chapel and the "secret" of cancer cachexia

The clinical journey of chronic diseases, including cancer, renal failure and chronic obstructive pulmonary disease, is frequently characterised by the progressive deterioration of nutritional status, leading to increased morbidity and mortality, and impinges upon quality of life. Diseaseassociated malnutrition is characterised by anorexia and reduced food intake, but nutritional depletion cannot be accounted for by insuffcient energy intake only. Indeed, wasting of muscles and adipose tissue also occurs, which is not suppressed by the provision of nutrients. Diseaseassociated malnutrition is defned as the anorexia-cachexia syndrome, to differentiate this clinical condition from malnutrition resulting from simple starvation, which responds to nutritional support. The pathogenesis of the anorexia-cachexia syndrome is multifactorial, but moderate yet persistent infammation plays a prominent role in mediating the observed changes of eating behavior and of the metabolism of peripheral tissues. Peripheral tissue wasting and disease-associated anorexia have been classically considered as involving different molecular pathways, the former being mediated by increased muscle proteolysis and adipose tissue lipolysis, the latter being induced by neurochemical alterations. However, recent data seem to support the concept that disease-associated anorexia and wasting represent the clinical phenotypes of common pathogenic mechanisms, involving brain areas controlling energy homeostasis. In this regard, the different clinical pictures of disease-associated malnutrition, characterised by a variety of combinations of anorexia and wasting, refect the different interactions occurring between the genotypes of the host and the underlying disease. Therefore, it has been proposed that the anorexia-cachexia syndrome is better defned as cachexia, which now encompasses the countless clinical expressions of the host's response to a chronic insult. Surprisingly, such a unifying concept was already left by Michelangelo as a hidden message on the ceiling of the Sistine Chapel 500 years ago.