Diaphragm muscle sarcopenia in Fischer 344 and Brown Norway rats

Abstract

New Findings: What is the central question of this study? Several rat models are commonly used to study the physiology of ageing (e.g. Fischer 344 and Brown Norway rats are recommended by the USA National Institute of Ageing). Diaphragm muscle sarcopenia (ageing-related muscle weakness and atrophy) remains incompletely described in these rat models. What is the main finding and its importance? Diaphragm muscle sarcopenia is present in both the Fischer 344 and Brown Norway rat strains, but appears more pronounced in Fischer 344 rats. The risk for respiratory diseases increases in adults >65 years of age, which may be attributable in part to ageing-related weakening and atrophy (i.e. sarcopenia) of the diaphragm muscle (DIAm). The 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, i.e. 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 evaluated comprehensively in either strain. Thus, the present study examined DIAm sarcopenia in older adult F344 (24 months old, 50% survival) and BN rats (32 months old, 50% survival), compared with young adult (6-month-old) 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 the cross-sectional area of type I and IIa DIAm fibres was unchanged in both F344 and BN rats, the 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.