Sarcopenia is the age-related reduction of muscle mass and specific force. In previous studies, we found that sarcopenia of the diaphragm muscle (DIAm) is evident by 24 mo of age in both rats and mice and is associated with selective atrophy of type IIx and IIb muscle fibers and a decrease in maximum specific force. These fiber type-specific effects of sarcopenia resemble those induced by DIAm denervation, leading us to hypothesize that sarcopenia is due to an age-related loss of phrenic motor neurons (PhMNs). To address this hypothesis, we determined the number of PhMNs in young (6 mo old) and old (24 mo old) Fischer 344 rats. Moreover, we determined age-related changes in the size of PhMNs, since larger PhMNs innervate type IIx and IIb DIAm fibers. The PhMN pool was retrogradely labeled and imaged with confocal microscopy to assess the number of PhMNs and the morphometry of PhMN soma and proximal dendrites. In older animals, there were 22% fewer PhMNs, a 19% decrease in somal surface area, and a 21% decrease in dendritic surface area compared with young Fischer 344 rats. The age-associated loss of PhMNs involved predominantly larger PhMNs. These results are consistent with an age-related denervation of larger, more fatigable DIAm motor units, which are required primarily for high-force airway clearance behaviors. NEW & NOTEWORTHY Diaphragm muscle sarcopenia in rodent models is well described in the literature; however, the relationship between sarcopenia and frank phrenic motor neuron (MN) loss is unexplored in these models. We quantify a 22% loss of phrenic MNs in old (24 mo) compared with young (6 mo) Fischer 344 rats. We also report reductions in phrenic MN somal and proximal dendritic morphology that relate to decreased MN heterogeneity in old compared with young Fischer 344 rats.

The risk for respiratory diseases increases in adults >65 years of age, which may be partially due to ageing-related weakening and atrophy (i.e., sarcopenia) of the diaphragm muscle (DIAm). However, mechanisms underlying DIAm sarcopenia remain unknown. Based on existing evidence, we hypothesized that sarcopenia is most evident in type IIx and/or IIb DIAm fibres comprising more fatigable motor units. Currently, the USA National Institute on Aging supports Fischer 344 (F344) and Brown Norway (BN) rat strains for ageing related research, yet DIAm sarcopenia has not been comprehensively evaluated in either strain. Thus, the current study examined DIAm sarcopenia in older adult (24 month, 50% survival) F344 and (32 month, 50% survival) BN rats, compared to young adult (6 month) F344 and BN rats. Measurements of contractility, contractile protein concentration, fibre type distribution and fibre cross-sectional area were obtained from midcostal DIAm strips. Maximal specific force was reduced by ∼24% and ∼13% in older F344 and BN rats, respectively. Additionally, although cross-sectional area of type I and IIa DIAm fibres was unchanged in both F344 and BN rats, cross-sectional area of type IIx and/or IIb DIAm fibres was reduced by ∼20% and ∼15% in F344 and BN rats, respectively. Thus, although there was ageing-related DIAm weakness and atrophy, selective to type IIx and/or IIb DIAm fibres in both F344 and BN rats, the sarcopenic phenotype was more pronounced in F344 rats.