As a greater proportion of the population is surviving to very old ages, the public health burden of aging-related disability, and the associated increases in utilization of medical care and need for long-term care, has become a critical concern. As a result, it has become imperative to identify risk factors for disability and establish therapies that are effective for preventing or improving these risk factors. While there is likely a common pathway of sarcopenia (loss of muscle mass and strength/contractility) underlying loss of physical function with age, little is known regarding the biological factors that are fundamental for the progression of this process. However, our work, as well as others, points to an important role for chronic/persistent, sub-clinical inflammation in the development of sarcopenia and physical disability, thus highlighting the need for novel, effective treatments against chronic inflammation in this age group.
The biological cascade of events comprising the body’s natural defenses against injury or infection is a vital part of the immune system. Typically, this process is an acute response, resulting in rapid increases in inflammatory mediators that are released into the circulation. For example, blood concentrations of the acute phase reactant, C reactive protein (CRP), can increase greater than 1000-fold in response to infection or trauma. However, several definitive studies now provide convincing data that persistent, yet very slight, elevations in systemic biomarkers of inflammation, even when within the clinically normal range, are prospective risk factors for several adverse health conditions, particularly cardiovascular disease. Importantly, in the elderly, inflammation is also a strong predictor of both disability and mortality—even in the absence of clinical disease. Most notably, chronic inflammation contributes to the loss of skeletal muscle mass and function, leading to earlier onset of disability (25
). Much higher concentrations of pro-inflammatory cytokines and acute phase reactants are seen in the elderly compared to middle-aged or younger adults, and several cytokines have direct, detrimental effects on skeletal muscle that lead to loss of myofibers and disruption of contractile function per se
). As such, we posit that the inflammatory pathway is a potential biological target for interventions to reduce risk of disability in the frail elderly.
Although chronic inflammation is now thought to be an important contributor to aging-related disability, there are no known definitive treatments for reducing this condition in the elderly. Certainly, use of anti-inflammatory medications may reduce inflammation, but side effects of these medications are likely to reduce their clinical application for the on-going treatment of persistent inflammation. As such, presently none of the pharmaceutical agents with anti-inflammatory effects are approved for the treatment of sarcopenia or aging-related loss of function. On the other hand, regular exercise is the only therapy found to consistently improve physical function in older, frail adults. However, since a single bout of exercise induces an inflammatory response that is similar to that induced by infection or trauma, there is controversy surrounding whether or not increasing physical activity may be effective for reducing chronic inflammation in the long-term, especially in the frail elderly. Yet, recent randomized, controlled trial data from our group provide promising evidence, and advances the hypothesis, that regular exercise may indeed be an effective treatment for chronic inflammation. This article highlights the findings from our studies, and those of others in this area, which provide evidence, and suggest mechanisms, for an effect of increasing physical activity on lowering chronic, sub-clinical inflammation in this vulnerable population at high risk for disability.