Sarcopenia in aging, obesity, and cancer

Sarcopenia, defined as loss of muscle mass, strength and physical performance, is a hallmark of aging and is invariably associated with perturbation of amino acid metabolism, increased muscle protein catabolism relative to anabolism, and loss of muscle fibers. Sarcopenia may be associated with general loss of body mass, or it may also occur along with obesity [sarcopenic obesity (SO)]. Although sarcopenia is associated with multiple comorbidities in older adults, its effects may even be more severe in patients with malignant disease where it has been shown to contribute to poor surgical outcomes, increased chemotherapy toxicity associated with both cytotoxic and targeted agents, as well as adversely impacting survival. While development of sarcopenia is a common age-related phenomenon, the associated catabolic processes appear to be promoted by physical inactivity, inadequate nutrition, and systemic low-grade inflammation, as well as intrinsic muscle and molecular changes, including mitochondrial dysfunction and impaired muscle stem cell regenerative capacity. Increased physical activity and adequate protein intake can reduce incidence and severity of sarcopenia in cancer patients, but many older cancer patients do not meet physical activity and nutrition recommendations, and cancer treatment can make it more difficult to make favorable lifestyle changes. Sarcopenia is discussed in terms of its adverse clinical consequences in older subjects and particularly, in older patients with cancer. Contributions of lifestyle, molecular, and cellular factors are likewise reviewed with suggestions for interventions to improve sarcopenia and its comorbid sequalae.