Journal of Cachexia, Sarcopenia and Muscle最新文献

Grip strength is a robust biomarker showing good reliability^{1, 2} and prediction of negative health outcomes.^{3, 4} Low grip strength is associated with disability and premature death^5-9 and is more strongly associated with frailty than chronological age.¹⁰ Accordingly, recent updates to consensus definitions of sarcopenia focus on low grip strength as the primary characteristic as opposed to low muscle mass.^{11, 12} Because rodent models are indispensable tools in aging research, scientists have reverse-translated grip testing as a key outcome in the context of sarcopenia.^13-16 Serendipitous development of preclinical grip testing has resulted in a variety of protocols that have not been extensively examined and compared.^{13-15, 17} Variability, due to motivation, temperament, and other factors such as pain, is inherent in preclinical behavioural assessments.¹⁸ Limited research has focused on standardizing preclinical grip testing, validation of methods against other functional measures, and investigating how preclinical grip data compare to data from humans and whether these tests even measure the same construct. Additionally, prior work has not examined between-day reliability of grip testing in rodents. This work was undertaken to inform rigorous preclinical grip testing.

Differences between clinical and preclinical grip must be considered when reverse translating methods to mice. Clinical grip testing is volitional whereas preclinical testing depends on reflexive responses. Prior clinical studies have consistently shown ICC ≥ 0.80 for repeated grip strength testing.¹ No data is available regarding the reliability of grip strength methods in mouse models. One study tested grip strength across three successive trials at a single study timepoint (ICC ranging 0.363–0.803) but did not assess reliability across days.²⁴ Our study showed that preclinical grip testing methods are less reliable compared to prior clinical studies. Based on CV, all limb grip testing was the most reliable method; based on ICC, bilateral hindlimb and forelimb grip testing were the most reliable methods. Thus, when choosing a method for grip assessment in aged mice where hindlimb assessment is critical, both all limb and bilateral hindlimb methods appear to be the best options for repeatability. Of note, how mice are grasped, tail or scruffing, was not assessed herein, but might impact results. Thus, further work is needed to better refine preclinical grip testing protocols.

The relationships between grip strength and indices of muscle mass were explored in a clinical cohort to compare these same relationships in mice. The age-related differences in grip strength noted in both our clinical and preclinical age comparisons were mor

There is increasing evidence that neurodegenerative disorders including the Parkinsonian syndromes are associated with impaired skeletal muscle health, manifesting as wasting and weakness. Many of the movement problems, lack of muscle strength and reduction in quality of life that are characteristic of these syndromes can be attributed to impairments in skeletal muscle health, but this concept has been grossly understudied and represents an important area of unmet clinical need. This review describes the changes in skeletal muscle health in idiopathic Parkinson's disease and in two atypical Parkinsonian syndromes, the most aggressive synucleinopathy multiple system atrophy, and the tauopathy progressive supranuclear palsy. The pathogenesis of the skeletal muscle changes is described, including the contribution of impairments to the central and peripheral nervous system and intrinsic alterations. Pharmacological interventions targeting the underlying molecular mechanisms with therapeutic potential to improve skeletal muscle health in affected patients are also discussed. Although little is known about the mechanisms underlying these conditions, current evidence implicates multiple pathways and processes, highlighting the likely need for combination therapies to protect muscle health and emphasizing the merit of personalized interventions for patients with different physical capacities at different stages of their disease. As muscle fatigue is often experienced by patients prior to diagnosis, the identification and measurement of this symptom and related biomarkers to identify early signs of disease require careful interrogation, especially for multiple system atrophy and progressive supranuclear palsy where diagnosis is often made several years after onset of symptoms and only confirmed post-mortem. We propose a multidisciplinary approach for early diagnosis and implementation of personalized interventions to preserve muscle health and improve quality of life for patients with typical and atypical Parkinsonian syndromes.