Functional Impact of Diaphragm Muscle Sarcopenia in Fischer 344 Rats

Abstract

The diaphragm muscle (DIAm) is the primary inspiratory muscle responsible for force generation across a range of ventilatory and higher force airway clearance behaviors throughout life. Our laboratory has previously reported DIAm sarcopenia, the age‐related atrophy and weakening of skeletal muscle, in multiple rodent models. Interestingly, in Fischer 344 rats, there is an increase in body mass from 6 to 24 months of age, which is greater in females (~140%) than in males (~110%), suggesting potential sex‐related differences in the manifestation of sarcopenia. Transdiaphragmatic pressure (Pdi) measurements provide information about force generation in vivo across a range of motor behaviors. The purpose of this study was to evaluate if there are sex‐related differences in DIAm sarcopenia, and if such differences translate to a functional impact on Pdi generation. We hypothesized that because of differences in weight gain, DIAm sarcopenia is more pronounced in male vs. female Fischer 344 rats, and that there is a greater impact of sarcopenia on maximum Pdi generated by bilateral phrenic nerve stimulation (Pdimax). Since Pdi generated across a range of ventilatory motor behaviors only requires <50% Pdimax, we also hypothesize that sarcopenia does not impair Pdi generation during ventilatory behaviors. Compared to 6‐month old rats, DIAm sarcopenia was apparent in ‐24‐month old rats of both sexes with a 30% reduction in maximum specific force. There was also a ~20% decrease in the cross‐sectional area of type IIx and/or IIb fibers with age, and this reduction was more pronounced in male rats. Thus, these mixed results do not entirely support our hypothesis of more pronounced DIAm sarcopenia in male rats. However, DIAm sarcopenia was associated with a ~30% decrease in Pdimax that was comparable between male and female rats. Importantly, the Pdi generated during ventilatory behaviors was unaffected by DIAm sarcopenia, even during more forceful ventilatory efforts induced by complete oropharyngeal airway occlusion. Although ventilatory behaviors are preserved with aging, a reduction in Pdimax indicates an impaired ability of the DIAm to generate higher force expulsive airway clearance behaviors necessary for maintaining airway patency.Support or Funding InformationNIH R01‐AG044615 and T32‐HL105355This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.