Systemic Inflammation in the Genesis of Frailty and Sarcopenia: An Overview of the Preventative and Therapeutic Role of Exercise and the Potential for Drug Treatments.

Abstract

The clinical, pathological and biological characteristics of frailty and sarcopenia are becoming better understood and defined, including the role of systemic inflammation. It is increasingly apparent that in older adults there is a tendency for the innate immune network to shift toward a pro-inflammatory setting, often due to the presence of chronic inflammatory diseases but also associated with age alone in some individuals. Furthermore, acute inflammation tends to resolve more slowly and less completely in many elderly people. Inflammation contributes to the pathogenesis of sarcopenia and other components of the frailty syndrome. Blood levels of inflammatory cytokines and acute phase proteins, are reduced by exercise, and there is a growing body of epidemiological, observational and intervention research that indicates that regular moderate exercise improves strength, function, morbidity and mortality in middle-aged and elderly adults. There is also an increasing awareness of the potential role of drugs to ameliorate inflammation in the context of frail old age, which might be particularly useful for people who are unable to take part in exercise programs, or as adjunctive treatment for those who can. Drugs that shift the innate immune biochemical network toward an anti-inflammatory setting, such as methyl-xanthines and 4-amino quinolones, could be of value. For example, theophylline has been shown to induce a 20 percent fall in pro-inflammatory tumor necrosis factor (TNF) and 180 percent rise in anti-inflammatory interleukin-10 production by peripheral blood monocytes, and a fall of 45 percent in interferon-gamma (IF-gamma) release. Such properties could be of therapeutic benefit, particularly to re-establish a less inflamed baseline after acute episodes such as sepsis and trauma.