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Catabolic Wasting - Cachexia And Sarcopenia

Background

A number of factors often converge to cause catabolic wasting. Malnutrition due to reduced food consumption or impaired nutrient absorption occurs frequently in later stages of chronic disease and can cause marked loss of muscle and fat tissue. Even though cachexia is typically accompanied by loss of appetite, it rarely responds to increased food intake alone (Siddiqui 2006; Solheim 2013). Dehydration is another important contributor, as loss of fluid results in reduced weight (Morley 2006).

Inflammation also plays a major role in deterioration of body mass among individuals with cachexia (Morley 2006). Both acute and chronic illness can cause marked increases in the production of inflammatory cell-signaling molecules called cytokines. These inflammatory mediators alter numerous metabolic processes, resulting in reduced muscle protein synthesis and increased muscle protein breakdown. Several specific cytokines have been linked to cachexia including interleukin-1, interleukin-2, interleukin-6, interferon-γ, and tumor necrosis factor-alpha (TNF-α). Inflammatory cytokines activate a major metabolic regulator called nuclear factor kappa B (NF-κB), which in turn drives several physiological changes that promote tissue deterioration. Inflammatory cytokines also stimulate the release of the adrenal hormone cortisol and neurotransmitter hormones called catecholamines; both cortisol and catecholamines can exacerbate catabolic wasting by disrupting muscle cell metabolism and altering the basal metabolic rate (Siddiqui 2006; Morley 2006).

Reductions in levels of testosterone and insulin-like growth factor-1 (IGF-1) are thought to play an important role in catabolic wasting as well. Both testosterone and IGF-1 exert anabolic actions in muscle tissue, so declining levels of these hormones can lead to reduced muscle mass (Morley 2006).

Sarcopenia involves multiple factors including increased inflammation, insulin resistance, oxidative damage, and protein breakdown; reduced protein synthesis; changes in hormone levels (such as lower levels of growth hormone and testosterone); dysfunction of blood vessels and nerves; and damage to mitochondria (organelles that produce cellular energy) (Semba 2007; Thomas 2007; Zacker 2006; Kim 2011; Moon 2013; Marzetti 2009; Marzetti 2013).