Impact of sarcopenia on diaphragm muscle fatigue

Abstract

New Findings What is the central question of this study?Is the residual force generated by the diaphragm muscle after repeated activation reduced with sarcopenia, and is the residual force generated after fatiguing activation sufficient to sustain ventilatory behaviours of diaphragm muscle in young and old rats? What is the main finding and its importance?After diaphragm muscle fatigue, the residual specific force after 120 s of repeated stimulation was unaffected by ageing and was sufficient to accomplish ventilatory behaviours, but not expulsive manoeuvres (e.g. coughing). The inability to perform expulsive behaviours might underlie the increased susceptibility of older individuals to respiratory tract infections. Abstract Type IIx and/or IIb diaphragm muscle (DIAm) fibres make up more fatigable motor units that are more vulnerable to sarcopenia, i.e. age‐associated reductions of specific force and cross‐sectional area. In contrast, type I and IIa DIAm fibres form fatigue‐resistant motor units that are relatively unchanged with age. The fatigue resistance of the DIAm is assessed by normalizing the residual force generated after a period of repeated supramaximal stimulation (e.g. 120 s) to the initial maximal force. Given that sarcopenia primarily affects more fatigable DIAm motor units, apparent fatigue resistance improves with ageing. However, the central question is whether there is an ageing‐related difference in the residual force generated by the DIAm after repeated stimulation and whether this force is sufficient to sustain ventilatory behaviours of DIAm. In 6‐ and 24‐month‐old Fischer 344 rats, we assessed the loss of ex vivo DIAm force throughout 120 s of repeated supramaximal stimulation at 10, 40 and 75 Hz. We found that relative fatigue resistance improved in older rats at 40 and 75 Hz stimulation. Across all stimulation frequencies, DIAm residual force was unchanged with age (∼5 N cm−2). We conclude that ageing increases the relative contribution of type I and IIa fibres to DIAm force, with decreased contributions of type IIx and/or IIb fibres. The residual force generated by the DIAm after repeated stimulation is sufficient to accomplish ventilatory behaviours, regardless of age.

Diaphragm muscle sarcopenia into very old age in mice

“…The American Thoracic Society and the European Respiratory Society Statement on Respiratory Muscle Testing (European & Society, ) supports the clinical use of Pdi to study force generation across the full range of motor behaviors accomplished by respiratory muscles such as the DIAm. Ventilatory behaviors can be accomplished across a number of species by generating forces that represent only ~10%–30% of the maximal force generating capacity of the DIAm (Fogarty, Mantilla, & Sieck, ; Mantilla et al, ; Sieck, ). However, higher forces are necessary to accomplish expulsive, airway clearing behaviors such as coughing or sneezing as well as defecation, micturition, and parturition, where co‐activation of the DIAm and abdominal muscles is required (Milano, Grelot, Bianchi, & Iscoe, ; Rybak et al, ; Shannon, Baekey, Morris, & Lindsey, ).…”

Strong links in a weak chain: skeletal muscle fibres in amyotrophic lateral sclerosis

“…), there is a selective atrophy of type IIx and/or IIb muscle fibres and a sparing of type I and IIa fibres (Fogarty et al . ). In the present study, homogenate preparation showing the expression of MyHC SLOW (referred as MHC I in the study) is negligible compared to MyHC 2A and MyHC 2B (referred as MHC IIa and IIb, respectively, in the study) precluded this assessment.…”

“…Indeed, a major component of fibre‐typing of skeletal muscles is their fatigability, with type I and IIa fibres exhibiting minimal fatigue (due to high metabolic capacity) and type IIx and IIb fibres exhibiting higher levels of fatigue (due to lower metabolic capacity) (Fogarty et al . ). In their experiments, Cheng and colleagues made the fascinating observation that, far from impaired force production, FDB single skeletal muscle fibres from symptomatic SOD G93A mice display improved force generation during fatiguing stimulation protocols.…”

“…, Fogarty et al . , ). In this respect, preservation of the type IIa fibre cross‐sectional area (and the preservation of their contribution to FDB mass) would help to disambiguate the issue of whether or not force reduction due to atrophy of muscle mass was generalized (i.e.…”

Diaphragm muscle performance in ageing: A new perspective on an old story

“…In this issue of Experimental Physiology, Fogarty, Mantilla & Sieck (2019) extend a long-standing interest by this group in diaphragm muscle physiology, seeking to address two important questions.…”