Abstract
Influenza (flu) is problematic for the elderly with increased severity of infection and greater risk for hospitalization and death. Primary flu infection is limited to pulmonary epithelial cells; yet myalgias are a common symptom and elderly have increased risk for disability following flu infection. Our laboratory was the first to demonstrate a molecular link for this interaction by characterizing the impact of flu infection on muscle health in mice. Overall, flu leads to mobility impairments with induction of inflammatory and muscle degradation genes and downregulation of positive regulators of muscle growth. These effects are prolonged with aging, suggesting a direct link between flu infection and increased risk of disability in the elderly. We found upregulation of chemokines such as CXCL10, which promotes immune cell infiltration, in young and aged skeletal muscle tissue with dramatically higher and prolonged expression only in the aged muscle. Correspondingly, immunohistochemistry of murine gastrocnemius muscle revealed higher numbers of leukocytes (CD45+) during flu infection in young and aged mice with a prolonged elevation in the aged mice. Interestingly, an influx of T lymphocytes (CD45+CD3+) only occurred in aged muscle later in infection. It is possible that infiltrating T cells are causing undue harm to the aged muscle potentially hindering muscle regeneration and functional recovery. These findings allude to a cellular mechanism of flu-induced disability and provide the groundwork for development of therapeutic advances to help elderly maintain independence following flu infection.