Age-related alterations in human motor units properties and in muscle innervation profile

Abstract

Introduction: Mounting evidence suggests that motoneuron and neuromuscular junction (NMJ) degeneration, muscle fiber denervation and loss of motor units contribute to muscle wasting and weakness in old age. However, these aspects are still poorly investigated in humans. This study aimed at comparing the neuromuscular system integrity and function of young and older adults, with particular focus on NMJ and motor unit potential (MUP) characteristics. We hypothesized that older individuals would present altered electrophysiological properties and innervation profile. Methods: We recruited 55 healthy young individuals (YI) (aged 26.1±4.5 yr; 50% females) and 88 older individuals (OI) (aged 75.9±4.7 yr; 55% females). Muscle force was evaluated by isometric dynamometry, muscle morphology by ultrasound and neuromuscular excitability by compound motor unit action potential (CMAP). MUP properties and motor unit number estimate (iMUNE) were obtained by intramuscular electromyography (iEMG). In a sub-cohort of individuals (n=16 YI and n=34 OI), vastus lateralis (VL) muscle biopsies were obtained. We assessed denervation status by scoring neural cell adhesion molecule (NCAM) positive fibers. Generalized linear mixed models were carried out for iEMG data, while unpaired t-tests were carried out for all the other parameters. Results: OI showed alterations in muscle morphology when compared to YI, evident as smaller whole quadriceps cross-sectional area (p<0.001) and VL fiber diameter (p<0.01), together with smaller VL pennation angles (p<0.001) and fascicle lengths (p<0.05), resulting in an increased ultrasound sarcopenia index (p=0.001). Muscle force (p<0.001) and CMAP (p<0.001) were also largely impaired in OI, suggesting that muscle function and neuromuscular excitability are considerably affected by aging. iEMG analysis revealed changes in MUP turns (p<0.001), near fiber (NF) MUP duration (p<0.001) and NF count (p<0.001) in OI, pointing towards an increased MUP complexity, in absence of sex differences. The iMUNE was reduced (p<0.001) and the NMJ transmission stability was significantly altered in OI, as suggested by elevated NF jiggle (p<0.001) and segmented jitter (p<0.05). These electrophysiological alterations seem likely due to altered muscle innervation profile, as highlighted by an increased percentage of NCAM-positive fiber (p<0.001). Conclusions: This study showed that changes in muscle morphology and function, MUP properties, motor units loss and denervation status occur in older humans; these may be serve as useful markers of human neuromuscular aging. The present work was funded by PRIN project NeuAge (2017CBF8NJ_001) to MVN and the Milky Way Foundation, the Baxter Foundation, and the Li Ka Shing Foundation to HMB. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.