Greater Skeletal Muscle Fat Infiltration Is Associated With Higher All-Cause and Cardiovascular Mortality in Older Men

Increased accumulation of fat around and within nonadipose tissue organs that normally contain only small amounts of fat, such as in liver, heart, and skeletal muscle, can impair the normal physiological function of those organs (1). This “ectopic fat” storage is now recognized as a risk factor for several chronic diseases, in particular type 2 diabetes (T2D) and cardiovascular disease (CVD), independent of general obesity (2–9). Some propose that the tendency to accumulate adipose tissue in ectopic depots may be explained by inadequate function and capacity of subcutaneous depot to store excess fat (10,11), increased fatty acid transport, uptake and storage, and reduced fatty acid oxidation (2,12,13), and/or increased macrophage infiltration which inhibits adipocyte differentiation (14). Ectopic fat within and around skeletal muscle (known as myosteatosis) is a unique ectopic fat depot that is associated with poor metabolic and musculoskeletal health, and with accelerated aging (1,5,9,15–22). Specifically, myosteatosis has been identified as a risk factor for insulin resistance and T2D (16,22), increased risk of osteoporotic fractures (18,21), decreased muscle strength and mobility loss (15,19), reduced physical performance (23), and impaired longevity (20). Previous studies showed that skeletal muscle fat infiltration increases with advancing age (24), and that elderly individuals have greater myosteatosis (25,26) compared to younger individuals. Despite the emerging role of myosteatosis as an independent risk factor for metabolic dysfunction and other aging-related disorders, no previous studies have examined its association with mortality among older populations recruited without regard to their health status. Thus, in the current study, we evaluated the relationship between myosteatosis and mortality in a cohort of community-dwelling older men. We tested if this relationship was independent of total body and trunk fat, muscle size, lifestyle factors, comorbidities, frailty, and medications that may influence skeletal muscle metabolism. Given its important role in cardio-metabolic health, we hypothesized that increased myosteatosis would be associated with a greater risk of all-cause and CVD mortality.