Ugo Carraro

Physical exercise in aging human skeletal muscle increases mitochondrial calcium uniporter expression levels and affects mitochondria dynamics.

Age‐related sarcopenia is characterized by a progressive loss of muscle mass with decline in specific force, having dramatic consequences on mobility and quality of life in seniors. The etiology of sarcopenia is multifactorial and underlying mechanisms are currently not fully elucidated. Physical exercise is known to have beneficial effects on muscle trophism and force production. Alterations of mitochondrial Ca2+ homeostasis regulated by mitochondrial calcium uniporter (MCU) have been recently shown to affect muscle trophism in vivo in mice. To understand the relevance of MCU‐dependent mitochondrial Ca2+ uptake in aging and to investigate the effect of physical exercise on MCU expression and mitochondria dynamics, we analyzed skeletal muscle biopsies from 70‐year‐old subjects 9 weeks trained with either neuromuscular electrical stimulation (ES) or leg press. Here, we demonstrate that improved muscle function and structure induced by both trainings are linked to increased protein levels of MCU. Ultrastructural analyses by electron microscopy showed remodeling of mitochondrial apparatus in ES‐trained muscles that is consistent with an adaptation to physical exercise, a response likely mediated by an increased expression of mitochondrial fusion protein OPA1. Altogether these results indicate that the ES‐dependent physiological effects on skeletal muscle size and force are associated with changes in mitochondrial‐related proteins involved in Ca2+ homeostasis and mitochondrial shape. These original findings in aging human skeletal muscle confirm the data obtained in mice and propose MCU and mitochondria‐related proteins as potential pharmacological targets to counteract age‐related muscle loss.

Anthropometry of Human Muscle Using Segmentation Techniques and 3D Modelling: Applications to Lower Motor Neuron Denervated Muscle in Spinal Cord Injury

This chapter describes a novel approach to determining muscle anthropometry using medical imaging and processing techniques to evaluate and quantify: (1) progression of atrophy in permanent muscle lower motor neuron (LMN) denervation in humans and (2) muscle recovery as induced by functional electrical stimulation (FES). Briefly, we used three-dimensional reconstruction of muscle belly and bone images to study the structural changes occurring in these tissues in paralyzed subjects after complete lumbar-ischiatic spinal cord injury (SCI). These subjects were recruited through the European project RISE, an endeavour designed to establish a novel clinical rehabilitation method for patients who have permanent and non-recoverable muscle LMN denervation in the lower extremities. This chapter describes the use of anthropometric techniques to study muscles in several states: healthy, LMN denervated-degenerated not stimulated, and LMN denervated-stimulated. Here, we have used medical images to develop three-dimensional models, including computational models of activation patterns induced by FES. Shape, volume and density changes were measured on each part of the muscles studied. Changes in tissue composition within both normal and atrophic muscle were visualized by associating the Hounsfield unit values of fat and connective tissue with different colours. The minimal volumetric element (voxel) is approximately ten times smaller than the volume analyzed by needle muscle biopsy. The results of this microstructural analysis are presented as the percentage of different tissues (muscle, loose and fibrous connective tissue, fat) in the total volume of the rectus femoris muscle; the results display the first cortical layer of voxels that describe the muscle epimisium directly on the three-dimensional reconstruction of the muscle. These analyses show restoration of the muscular structure after FES. The three-dimensional approach used in this work also allows measurement of geometric changes in LMN denervated muscle. The computational methods developed allow us to calculate curvature indices along the muscle’s central line in order to quantify changes in muscle shape during the treatment. The results show a correlation between degeneration status and changes in shape; the differences in curvature between control and LMN denervated muscle diminish with the growth of the latter. Bone mineral density of the femur is also measured in order to study the structural changes induced by muscle contraction and current flow. Importantly, we show how segmented data can be used to build numerical models of the stimulated LMN denervated muscle. These models are used to study the distribution of the electrical field during stimulation and the activation patterns.

Elektrostimulation komplett denervierter Muskulatur

Bei der klinischen Beurteilung peripherer Lahmungen wird zwischen kompletten und inkompletten Lasionen unterschieden.

Nonlinear Trimodal Regression Analysis of Radiodensitometric Distributions to Quantify Sarcopenic and Sequelae Muscle Degeneration.

Muscle degeneration has been consistently identified as an independent risk factor for high mortality in both aging populations and individuals suffering from neuromuscular pathology or injury. While there is much extant literature on its quantification and correlation to comorbidities, a quantitative gold standard for analyses in this regard remains undefined. Herein, we hypothesize that rigorously quantifying entire radiodensitometric distributions elicits more muscle quality information than average values reported in extant methods. This study reports the development and utility of a nonlinear trimodal regression analysis method utilized on radiodensitometric distributions of upper leg muscles from CT scans of a healthy young adult, a healthy elderly subject, and a spinal cord injury patient. The method was then employed with a THA cohort to assess pre- and postsurgical differences in their healthy and operative legs. Results from the initial representative models elicited high degrees of correlation to HU distributions, and regression parameters highlighted physiologically evident differences between subjects. Furthermore, results from the THA cohort echoed physiological justification and indicated significant improvements in muscle quality in both legs following surgery. Altogether, these results highlight the utility of novel parameters from entire HU distributions that could provide insight into the optimal quantification of muscle degeneration.

Muscle Assessment Using 3D Modeling and Soft Tissue CT Profiling

This chapter outlines the methods and applications of X-ray computed tomography (CT) imaging to analyze soft tissue and skeletal muscle density and volume in the context of modern challenges in the field of translational myology. The approaches described here use medical imaging processing techniques and computational methods to quantify muscle morphology, illustrate changes with 3D models, develop numerical profiles specific for each individual, and assess muscle changes due to targeted medical treatment.

Functional Electrical Stimulation of Skeletal Muscles in Aging and Premature Aging

All progressive muscle contractile impairments (including age-related muscle weakness) need permanent management. We discuss evidence that subclinical denervation contributes to atrophy and slowness of aged muscle, and we provide stimulation protocols for aged and denervated skeletal muscles. We describe in Sect. 11.1 the effects of home-based neuromuscular FES in elderly persons and then in Sect. 11.2 the diagnostics, training protocols, and clinical results of home-based functional electrical stimulation (h-b FES) for denervated–degenerated skeletal muscle tissue. Using molecular analyses, histological morphometry, and Muscle Color Computed Tomography, we evaluated muscles of elderly persons, showing that increased levels of muscle contractions induced by h-b FES reverse muscle weakness and atrophy both in sedentary seniors and in conus and cauda equina complete syndrome.

CT-Based Bone and Muscle Assessment in Normal and Pathological Conditions

This article outlines the methods and applications of threshold-based techniques to assess in vivo muscle and bone tissue distribution in normal and pathological conditions using computed tomography imaging. The approaches described here use medical imaging processing techniques and computational methods to study bone mechanical proprieties, analyze and quantify muscle morphology, visualize changes with 3-D models, develop subject-specific numerical profiles, and assess muscle and bone changes during clinical treatments.