Cellular mechanisms promoting cachexia and how they are opposed by sirtuins ¹

Many chronic diseases are associated with unintentional loss of body weight, which is termed "cachexia". Cachexia is a complex multifactorial syndrome associated with the underlying primary disease, and characterized by loss of skeletal muscle with or without loss of fat tissue. Patients with cachexia face dire symptoms like dyspnea, fatigue, edema, exercise intolerance, and low responsiveness to medical therapy, which worsen quality of life. Because cachexia is not a stand-alone disorder, treating primary disease - such as cancer - takes precedence for the physician, and it remains mostly a neglected illness. Existing clinical trials have demonstrated limited success mostly because of their monotherapeutic approach and late detection of the syndrome. To conquer cachexia, it is essential to identify as many molecular targets as possible using the latest technologies we have at our disposal. In this review, we have discussed different aspects of cachexia, which include various disease settings, active molecular pathways, and recent novel advances made in this field to understand consequences of this illness. We also discuss roles of the sirtuins, the NAD⁺-dependent lysine deacetylases, microRNAs, certain dietary options, and epigenetic drugs as potential approaches, which can be used to tackle cachexia as early as possible in its course.