Aging enhances pro-atrogenic gene expression and skeletal muscle loss following respiratory syncytial virus infection

TL;DR

Aging makes mice more vulnerable to muscle loss after RSV infection, with increased inflammation and atrophy-related gene activity.

Contribution

The study reveals how RSV infection causes muscle atrophy in aged mice through increased atrogenic gene expression and inflammation.

Findings

RSV infection caused greater weight loss and inflammation in aged mice compared to young mice.

Aged mice showed reduced muscle weight and fiber size, along with elevated Atrogin-1 and MuRF-1 expression.

Muscle atrophy gene expression in aged mice correlated with IL-6 levels in the lungs.

Abstract

Aging and many age-related health conditions are associated with skeletal muscle loss. Furthermore, older adults are more susceptible to severe respiratory infections, which can in turn lead to muscle wasting. The mechanisms by which respiratory viral infection can impact skeletal muscle in older adults are not well understood. We determined the effects of acute infection with respiratory syncytial virus (RSV) on the lung and skeletal muscle of aged mice. RSV infection caused more severe disease in aged mice with enhanced weight loss, reduced feeding, higher viral load, and greater airway inflammation. Aged but not young mice showed decreased leg muscle weight at the peak of illness and decreased size of leg muscle fibers. Aged mice increased muscle-specific expression of atrophy-promoting enzymes (Atrogin-1 and MuRF-1) and failed to increase the rate of muscle protein synthesis during RSV infection. In aged mice, the changes in Atrogin-1 and MuRF-1 gene expression in skeletal muscle correlated with IL-6 levels in the lungs. These findings indicate that RSV infection of aged mice provides a model for studying the diverse adverse systemic consequences of respiratory viral infections on health and wellbeing in older adults.

The online version contains supplementary material available at 10.1007/s11357-024-01370-2.

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