Scientific Programme
Sports and Exercise Medicine and Health
IS-MH01 - Exercise, Aging, and Metabolic Health: Decoding Intracellular and Extracellular Redox Signals
Date: 03.07.2024, Time: 09:30 - 10:45, Lecture room: M1
Description
In the 30+ years since the first descriptions of increased generation of a reactive oxygen species (superoxide) and nitric oxide by contracting skeletal muscle, a great deal of information has been published on the specific mechanisms of generation and the potential functions of these species and the secondary products derived from them. Despite this extensive scientific progress, practical applications that utilize the increasing knowledge of muscle redox pathways have been slow to emerge, although this is changing rapidly with the identification of the specific pathways involved in redox control and functional changes in muscle that can be attributed to redox regulation. Roles in the maintenance of muscle function during exercise are well established. Still, manipulations of skeletal muscle nitric oxide and NADPH oxidases are now recognized to have the potential to preserve respiratory function in heart and kidney diseases, and muscle-derived hydrogen peroxide functions as a signaling molecule regulating muscle stress responses to exercise mediates beneficial changes in glucose homeostasis post-exercise and muscle responses to focal denervation during aging. This session will highlight the latest developments in these areas and provide information on the potential for further redox translational developments in the health-enhancing physical activity area.
Chair(s)
Daniela Caporossi
University of Rome Foro Italico, Human Movement, Human and Health Sciences
Italy
Richard Davison
University of the West of Scotland, School of Health and Life Sciences
United Kingdom
Speaker A
Malcom Jackson
University of Liverpool, Institute of Ageing and Chronic Disease
United Kingdom
Read CVECSS Glasgow 2024: IS-MH01
Ageing induces attenuated responses of skeletal muscle to contractile activity: mechanisms and effects
Minor episodes of denervation of skeletal muscle fibres occur throughout life and are rapidly repaired. Substantial denervation of muscles occurs as a result of trauma and disease and can lead to severe atrophy and eventual loss of the muscle fibres. Age-related loss of skeletal muscle mass and function (sarcopenia) is associated with loss of innervation of groups of muscle fibres and loss of motor neurons. Ageing related changes in muscle are also associated with dysregulation in the generation and/or handling of reactive oxygen species (ROS) in muscle. In normal physiology generation of ROS and redox signalling pathways play an important role in mediating specific responses of skeletal muscle to contractile activity. This process involves generation of ROS at specific sub-cellular sites in the muscle fibres. We have investigated the role of denervation in controlling ROS activities within muscle. Data from experimental models in which ROS regulation is modified, such as mice lacking SOD1 and those in which muscles undergo experimental denervation indicate that loss of motor neuron integrity leads to large increases in mitochondrial peroxide generation in the denervated muscle fibres. Furthermore, this increase occurs in mitochondria of neighbouring innervated fibres indicating a propagation of the process within the muscle. This local increased generation of peroxides by mitochondria appears to affect overall muscle redox homeostasis leading to oxidative damage and to dysregulation of adaptive responses to contractile activity. Implications for prevention and treatment of sarcopenia will be discussed.
Speaker B
Carlos Henriquez-Olguin
University of Copenhagen, Department of Nutrition, Exercise and Sports
Denmark
Read CVECSS Glasgow 2024: IS-MH01
Subcellular Redox Signaling Controlling Skeletal Muscle Metabolism in Health and Disease
Regular physical activity is a cornerstone of health, staving off aging and diseases such as type II diabetes and cardiovascular disease. Acute exercise introduces a multifaceted intracellular stress, with numerous post-translational modifications believed to underpin the health benefits of sustained exercise training. Reactive oxygen species (ROS) are posited to serve as second messengers, triggering cytoprotective adaptations such as the upregulation of enzymatic scavenger systems. However, a significant knowledge gap exists between the generation of oxidants in muscle and the exact mechanisms driving muscle adaptations. Over the past decade, our research has shed light on the compartmentalized sources of ROS—specifically mitochondria and the membrane-bound NADPH oxidase complexes (NOX)—and their contributions to immediate and long-term exercise responses. We discovered that NOX2, in particular, plays a pivotal role in the acute response to exercise, driving the expression of genes that underpin adaptation. Our innovative use of NOX2 inhibitors, mitochondria-targeted antioxidants, and advanced imaging techniques has revealed that NOX2 is a primary source of cytosolic H2O2 during exercise in vivo, essential for the translocation of the glucose transporter GLUT4 and subsequent glucose uptake in muscle. This presentation will describe the cellular mechanism of how exercise improves redox fitness in skeletal muscle to improve muscle function and insulin sensitivity.
Speaker C
Daniela Caporossi
University of Rome Foro Italico, Human Movement, Human and Health Sciences
Italy
Read CVECSS Glasgow 2024: IS-MH01
Exercise-induced systemic response: the role of circulating extracellular vesicles
Regular physical exercise (PE) leads to a systemic adaptation to redox homeostasis perturbation, one of the hallmarks of exercise adaptation. Extracellular vesicles (EVs) circulating in the body and secreted from various cell types, including skeletal muscle cells, contain various regulatory molecules and mediate intercellular communications and tissue cross-talk. Studies have shown that PE can alter the molecular composition of EVs, impacting their ability to communicate with other cells and modulate physiological processes. Considering that the health-related benefits of a physically active lifestyle are partially driven by various bioactive molecules released into the circulation during exercise, collectively termed “exerkines”, there has been a rapidly growing interest in the role of EVs cargo as “carriers” in the multi-systemic, adaptive response to exercise. Indeed, a potential mechanism by which plasma EVs released during exercise impact ageing and diseases related to redox impairment is increased delivery of redox components, such as redox transcription factors and antioxidants. Thexerciseis presentation will offer a general overview on the biology of exercise-induced EVs and their putative role on health maintainance and disease prevention, with a focus on redox homeostasis control.