Abstract
Although the influenza virus only infects the respiratory system, myalgias are commonly experienced during infection. In addition to a greater risk of hospitalization and death, older adults are more likely to develop disability following influenza infection; however, this relationship is understudied. We hypothesized that upon challenge with influenza, aging would be associated with functional impairments, as well as upregulation of skeletal muscle inflammatory and atrophy genes. Infected young and aged mice demonstrated decreased mobility and altered gait kinetics. These declines were more prominent in hind limbs and in aged mice. Skeletal muscle expression of genes involved in inflammation, as well as muscle atrophy and proteolysis, increased during influenza infection with an elevated and prolonged peak in aged mice. Infection also decreased expression of positive regulators of muscle mass and myogenesis components to a greater degree in aged mice. Gene expression correlated to influenza-induced body mass loss, although evidence did not support direct muscle infection. Overall, influenza leads to mobility impairments with induction of inflammatory and muscle degradation genes and downregulation of positive regulators of muscle. These effects are augmented and prolonged with aging, providing a molecular link between influenza infection, decreased resilience and increased risk of disability in the elderly.
Highlights
It is well established that immune function declines with aging
There are many pathways involved in protein degradation and atrophy, we focused on the ubiquitin proteasome pathway, primarily the muscle-specific E3 ubiquitin ligases atrogin-1 ( known as muscle atrophy F-box (MAFbx)) and muscle RING finger 1 (MuRF1), as the majority of literature to date shows increased atrogin-1 and/or MuRF1 expression at some point during almost all conditions of muscle wasting and atrophy [30]
Studies addressing the pathophysiology of flu infection typically focus on respiratory and immune systems, while those seeking to understand aging-related declines in mobility performance emphasize muscle biology and relevant neural systems
Summary
It is well established that immune function declines with aging Immunosenescence of both the innate and adaptive immune systems results in increased susceptibility to infection, as well as increased severity of infection in the elderly. Influenza (flu) tends to be problematic in the elderly with increased risk for serious complications and hospitalization. Even when death is avoided, elderly have increased risk of morbidity and disability from flu infection. Flu-related hospitalizations are associated with increased loss of independence [3] and long term declines in activities of daily living are observed post flu infection among nursing home residents [4]. Flu is among the leading causes of catastrophic disability and dramatic losses of activities of daily living in the elderly [5]. While it is known that prolonged hospitalization of the elderly is associated with decreased muscle mass and strength; flu infections, independent of hospitalization, have some degree of muscle involvement with myalgia among the common symptoms even in uncomplicated infections [6]
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