System Dysfunction

Dysfunction of key organ systems might explain the phenomenon of frailty. This would include musculo-skeletal abnormalities (e.g., sarcopenia) (Marcell 2003; Doherty 2003; Vanltallie 2003), endocrine deficiency states (e.g., gonadal hormones, DHEA, growth hormone/ IGF-1) (Morley et al., 2005), or immune dysfunction (e.g., high levels of inflammatory markers like TNF-a and IL-6) (Cohen 2000). It is not felt, though, that frailty arises from a single system problem (i.e., frailty ^ sarcopenia). There is widespread agreement that a core feature of frailty is the dysfunction of multiple physiologic systems. Different investigators have proposed various combinations of the following abnormalities as underlying frailty: diminished aerobic capacity; abnormalities in the neurological system (e.g., cognition, balance, and gait); musculoskeletal problems; precarious or deficient nutritional states; endocrine-metabolic dysfunction; stimulation of the immune system; and cardiovascular concerns (Buchner et al., 1992; Lipsitz et al., 1992); Lipsitz, 2002; Bortz, 2002; Campbell et al., 1997). Endocrine-immune dysregulation is a particularly favored partnering (Walston, 2004; Joseph et al., 2005; Ferrucci et al., 2003). At the present time there are no widely accepted animal models for frailty.

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