Impact of aging on diaphragm muscle function in male and female Fischer 344 rats

The diaphragm muscle (DIAm) is the primary inspiratory muscle in mammals and is active during ventilatory behaviors, but it is also involved in higher-force behaviors such as those necessary for clearing the airway. Our laboratory has previously reported DIAm sarcopenia in rats and mice characterized by DIAm atrophy and a reduction in maximum specific force at 24months of age. In Fischer 344 rats, these studies were limited to male animals, although in other studies, we noted a more rapid increase in body mass from 6 to 24 months of age in females (similar to 140%) compared to males (similar to 110%). This difference in body weight gain suggests a possible sex difference in the manifestation of sarcopenia. In mice, we previously measured transdiaphragmatic pressure (Pdi) to evaluate invivo DIAm force generation across a range of motor behaviors, but found no evidence of sex-related differences. The purpose of this study in Fischer 344 rats was to evaluate if there are sex-related differences in DIAm sarcopenia, and if such differences translate to a functional impact on Pdi generation across motor behaviors and maximal Pdi (Pdi(max)) elicited by bilateral phrenic nerve stimulation. In both males and females, DIAm sarcopenia was apparent in 24-month-old rats with a similar to 30% reduction in both maximum specific force and the cross-sectional area of type IIx and/or IIb fibers. Importantly, in both males and females, Pdi generated during ventilatory behaviors was unimpaired by sarcopenia, even during more forceful ventilatory efforts induced via airway occlusion. Although ventilatory behaviors were preserved with aging, there was a similar to 20% reduction in Pdi(max), which likely impairs the ability of the DIAm to generate higher-force expulsive airway clearance behaviors necessary to maintain airway patency.