Label-free quantitative protein profiling of the Human muscle during ultra-endurance exercise

National audienc

Protein profiling of the Human muscle during ultra-endurance exercise

National audienc

Vieillissement biologique du muscle squelettique chez l'Homme

Le thème des conférences portera sur : "La mobilité internationale pendant le doctorat"Vieillissement biologique du muscle squelettique chez l'Homme. Journée de la Recherche 2018, Ecole Doctorale Sciences, Ingénierie, Sant

Biological aging of skeletal muscle in humans

Grâce au rassemblement de la communauté de Lyon et de St Etienne, associant chercheurs, cliniciens, étudiants et entreprises, cette première conférence internationale visera à explorer comment et dans quelle mesure l’exercice peut être bénéfique pour les principales cellules de l’appareil locomoteur (muscle, tendon, os, cartilage, vaisseau). Cette journée offrira la possibilité de mettre en avant à la fois des travaux de recherche fondamentale réalisés à un niveau préclinique et des investigations conduites chez le volontaire sain ou sur des cohortes de patients. Des approches cellulaires, moléculaires et fonctionnelles seront mises en avant au cours de cette conférence.Présentation orale et posterAging is characterized by changes in body composition and particularly by a gradual loss of skeletal muscle mass, a phenomenon known as Sarcopenia. This age-related decline in muscle mass is accompanied by a loss of strength and a decline of physical performance, named Dynapenia. Both events decrease the autonomy and the quality of life of the individuals affecting about 40-50% of people over the age of 80. Nonetheless, inter-individual differences in prevalence of sarcopenia/dynapenia exist, as some remain fit and strong, whereas other become frail and weak when they get old. Until now, no study has examined the inter-individual variations of muscle tissue and its biomarkers. At the fiber level, age-related variations in skeletal muscle mass induce typological and capillarization modifications. Furthermore, the loss of muscle mass with aging could be associated with serious metabolic consequences or accumulation of intramyocellular lipid droplets. Immunohistochemical studies were performed with muscle biopsies from 30 healthy elderly men, aged 80 ±0.5 years selected from the PROgnostic indicator of cardiovascular and cerebrovascular events (PROOF) cohort, classified into three groups. On the basis of appendicular mass variation between two DEXA at mean interval of seven years, some people lose more muscle mass, named ”Lost”, others remain ”Stable”, and others ”Gain” muscle mass. The loss of skeletal muscle mass was associated with a reduction in Type-I fibers surface area (-24.6%), accompanied by a proportional loss of capillaries number around each fiber-type (CAF) and capillary-to-fiber perimeter exchange index (CFPE) (-15%, -10% respectively), compared to ”Stable” and ”Gain” groups. Also subjects from the ”Lost” group exhibited significant accumulation of intramyocellular lipid droplets in Type-I fibers compared to the ”Gain” (+23%). Lastly, this decline in muscle mass induced a remodeling of the extracellular matrix with an increase in the endomysium area (+12.2% vs Gain).If usually, it is recognized that chronological aging mainly affects Type-II motor units, our results suggest that biological aging is characterized by impairment of Type-I muscle fibers, their microvascular environment and oxidative metabolism for elderly men on their eighties

Biological aging of skeletal muscle in humans

Grâce au rassemblement de la communauté de Lyon et de St Etienne, associant chercheurs, cliniciens, étudiants et entreprises, cette première conférence internationale visera à explorer comment et dans quelle mesure l’exercice peut être bénéfique pour les principales cellules de l’appareil locomoteur (muscle, tendon, os, cartilage, vaisseau). Cette journée offrira la possibilité de mettre en avant à la fois des travaux de recherche fondamentale réalisés à un niveau préclinique et des investigations conduites chez le volontaire sain ou sur des cohortes de patients. Des approches cellulaires, moléculaires et fonctionnelles seront mises en avant au cours de cette conférence. Présentation orale et poster Grâce au rassemblement de la communauté de Lyon et de St Etienne, associant chercheurs, cliniciens, étudiants et entreprises, cette première conférence internationale visera à explorer comment et dans quelle mesure l’exercice peut être bénéfique pour les principales cellules de l’appareil locomoteur (muscle, tendon, os, cartilage, vaisseau). Cette journée offrira la possibilité de mettre en avant à la fois des travaux de recherche fondamentale réalisés à un niveau préclinique et des investigations conduites chez le volontaire sain ou sur des cohortes de patients. Des approches cellulaires, moléculaires et fonctionnelles seront mises en avant au cours de cette conférence. Présentation orale et posterGrâce au rassemblement de la communauté de Lyon et de St Etienne, associant chercheurs, cliniciens, étudiants et entreprises, cette première conférence internationale visera à explorer comment et dans quelle mesure l’exercice peut être bénéfique pour les principales cellules de l’appareil locomoteur (muscle, tendon, os, cartilage, vaisseau). Cette journée offrira la possibilité de mettre en avant à la fois des travaux de recherche fondamentale réalisés à un niveau préclinique et des investigations conduites chez le volontaire sain ou sur des cohortes de patients. Des approches cellulaires, moléculaires et fonctionnelles seront mises en avant au cours de cette conférence.Présentation orale et posterAging is characterized by changes in body composition and particularly by a gradual loss of skeletal muscle mass, a phenomenon known as Sarcopenia. This age-related decline in muscle mass is accompanied by a loss of strength and a decline of physical performance, named Dynapenia. Both events decrease the autonomy and the quality of life of the individuals affecting about 40-50% of people over the age of 80. Nonetheless, inter-individual differences in prevalence of sarcopenia/dynapenia exist, as some remain fit and strong, whereas other become frail and weak when they get old. Until now, no study has examined the inter-individual variations of muscle tissue and its biomarkers. At the fiber level, age-related variations in skeletal muscle mass induce typological and capillarization modifications. Furthermore, the loss of muscle mass with aging could be associated with serious metabolic consequences or accumulation of intramyocellular lipid droplets. Immunohistochemical studies were performed with muscle biopsies from 30 healthy elderly men, aged 80 ±0.5 years selected from the PROgnostic indicator of cardiovascular and cerebrovascular events (PROOF) cohort, classified into three groups. On the basis of appendicular mass variation between two DEXA at mean interval of seven years, some people lose more muscle mass, named ”Lost”, others remain ”Stable”, and others ”Gain” muscle mass. The loss of skeletal muscle mass was associated with a reduction in Type-I fibers surface area (-24.6%), accompanied by a proportional loss of capillaries number around each fiber-type (CAF) and capillary-to-fiber perimeter exchange index (CFPE) (-15%, -10% respectively), compared to ”Stable” and ”Gain” groups. Also subjects from the ”Lost” group exhibited significant accumulation of intramyocellular lipid droplets in Type-I fibers compared to the ”Gain” (+23%). Lastly, this decline in muscle mass induced a remodeling of the extracellular matrix with an increase in the endomysium area (+12.2% vs Gain).If usually, it is recognized that chronological aging mainly affects Type-II motor units, our results suggest that biological aging is characterized by impairment of Type-I muscle fibers, their microvascular environment and oxidative metabolism for elderly men on their eighties

Biological aging of skeletal muscle in humans

Grâce au rassemblement de la communauté de Lyon et de St Etienne, associant chercheurs, cliniciens, étudiants et entreprises, cette première conférence internationale visera à explorer comment et dans quelle mesure l’exercice peut être bénéfique pour les principales cellules de l’appareil locomoteur (muscle, tendon, os, cartilage, vaisseau). Cette journée offrira la possibilité de mettre en avant à la fois des travaux de recherche fondamentale réalisés à un niveau préclinique et des investigations conduites chez le volontaire sain ou sur des cohortes de patients. Des approches cellulaires, moléculaires et fonctionnelles seront mises en avant au cours de cette conférence.Présentation orale et posterAging is characterized by changes in body composition and particularly by a gradual loss of skeletal muscle mass, a phenomenon known as Sarcopenia. This age-related decline in muscle mass is accompanied by a loss of strength and a decline of physical performance, named Dynapenia. Both events decrease the autonomy and the quality of life of the individuals affecting about 40-50% of people over the age of 80. Nonetheless, inter-individual differences in prevalence of sarcopenia/dynapenia exist, as some remain fit and strong, whereas other become frail and weak when they get old. Until now, no study has examined the inter-individual variations of muscle tissue and its biomarkers. At the fiber level, age-related variations in skeletal muscle mass induce typological and capillarization modifications. Furthermore, the loss of muscle mass with aging could be associated with serious metabolic consequences or accumulation of intramyocellular lipid droplets. Immunohistochemical studies were performed with muscle biopsies from 30 healthy elderly men, aged 80 ±0.5 years selected from the PROgnostic indicator of cardiovascular and cerebrovascular events (PROOF) cohort, classified into three groups. On the basis of appendicular mass variation between two DEXA at mean interval of seven years, some people lose more muscle mass, named ”Lost”, others remain ”Stable”, and others ”Gain” muscle mass. The loss of skeletal muscle mass was associated with a reduction in Type-I fibers surface area (-24.6%), accompanied by a proportional loss of capillaries number around each fiber-type (CAF) and capillary-to-fiber perimeter exchange index (CFPE) (-15%, -10% respectively), compared to ”Stable” and ”Gain” groups. Also subjects from the ”Lost” group exhibited significant accumulation of intramyocellular lipid droplets in Type-I fibers compared to the ”Gain” (+23%). Lastly, this decline in muscle mass induced a remodeling of the extracellular matrix with an increase in the endomysium area (+12.2% vs Gain).If usually, it is recognized that chronological aging mainly affects Type-II motor units, our results suggest that biological aging is characterized by impairment of Type-I muscle fibers, their microvascular environment and oxidative metabolism for elderly men on their eighties

The coordinated up-regulation of the ubiquitin-proteasome and autophagy-lysosomal pathways strongly alters the Human muscle proteome during ultra-endurance exercise

ORGANIZING COMMITTEEChairs: Didier Attaix - Lydie Combaret - Daniel TaillandierDaniel Béchet - Agnès Claustre - Cécile Coudy-Gandilhon - Christiane Deval - Gérard Donadille - Cécile PolgeSCIENTIFIC COMMITTEEDidier Attaix - Lydie Combaret - Alfred L. Goldberg - Ron Hay - Germana Meroni - Marco Sandri - Daniel Taillandier - Keiji Tanaka - Simon S. WingSession 3 - AutophagyUltra-endurance exercise is associated with stresses that mechanically damage muscle cells and lead to injured proteins and organelles. Previous investigations provided evidence that ultra-endurance exercise is associated with a coordinated up-regulation of the ubiquitin-proteasome and autophagy-lysosomal proteolytic pathways (Jamart et al., 2012). The purpose of the present investigation was to assess the resulting modifications in the muscle proteome. Ten men, experienced ultra-endurance athletes ran for 24h on a treadmill. Muscle biopsy samples were taken from the vastus lateralis muscle 2h before starting and immediately after finishing exercise. Athletes ran 150+16 km with an effective running time of 18h:42min (±41min). Label-free quantitative protein profiling (‘Shot-Gun’) was performed (Théron et al., 2014) to quantify and compare proteomes before and after ultra-endurance running. Shot-Gun proteomics of the Human muscle homogenate identified 633 proteins, and among them 96 were differentially expressed after ultra-endurance running. Most of the proteins were under-represented after exercise. Functional interaction networks indicated that ultra-endurance strongly altered the mitochondrial proteome suggesting enhanced mitophagy. Our results also revealed important modifications related to the cytoskeleton, cytodetoxification, proteostasis and membrane repair. This study describes the most extensive proteomic analysis of Human muscle adaptation to ultra-endurance exercise. Many potential biomarkers may represent novel starting points to elucidate the mechanisms of muscle adaptation to extreme exercis

Association Between Physical Activity, Quadriceps Muscle Performance, and Biological Characteristics of Very Old Men and Women

International audienceAbstract The aim of the study was to evaluate the association between physical activity, knee extensors (KE) performance (ie, isometric strength and fatigability), and biological parameters (ie, muscle structural, microvascular, and metabolic properties) in healthy very old men and women. Thirty very old adults (82 ± 1 years, 15 women) performed an isometric Quadriceps Intermittent Fatigue (QIF) test for the assessment of KE maximal force, total work (index of absolute performance), and fatigability. Muscle biopsies from the vastus lateralis muscle were collected to assess muscle fibers type and morphology, microvasculature, and enzymes activity. Correlation analyses were used to investigate the relationships between physical activity (steps/day, actimetry), KE performance, and biological data for each sex separately. Men, compared to women, showed greater total work at the QIF test (44 497 ± 8 629 Ns vs 26 946 ± 4 707 Ns; p < .001). Steps per day were correlated with total work only for women (r = 0.73, p = .011). In men, steps per day were correlated with the percentage (r = 0.57, p = .033), shape factor (r = 0.75, p = .002), and capillary tortuosity of type IIX fibers (r = 0.59, p = .035). No other relevant correlations were observed for men or women between steps per day and biological parameters. Physical activity level was positively associated with the capacity of very old women to perform a fatiguing test, but not maximal force production capacity of the KE. Physical activity of very old men was not correlated with muscle performance. We suggest that very old women could be at higher risk of autonomy loss and increasing the steps per day count could provide a sufficient stimulus for adaptations in less active women

Muscle loss associated changes of oxylipin signatures during biological aging: an exploratory study from the PROOF cohort

Epub ahead of printCharacterizations of the multiple mechanisms determining biological aging are required to betterunderstand the etiology and identify early biomarkers of sarcopenia. Oxylipins are a large family ofsignaling lipids involved in the regulation of various biological processes that become dysregulatedduring aging.To investigate whether comprehensive oxylipin profiling could provide an integrated and finecharacterisation of the early phases of sarcopenia, we performed a quantitative targetedmetabolomics of oxylipins in plasma of 81-year old subjects from the PROOF cohort with decreased(n=12), stable (n=16) or increased appendicular muscle mass (n=14).Multivariate and univariate analyses identified significant and concordant changes of oxylipin profilesaccording to the muscle status. Of note, 90% of the most discriminant oxylipins were derived fromEPA and DHA and were increased in the sarcopenic subjects. The oxylipins signatures of sarcopenicsubjects revealed subtle activation of inflammatory resolution pathways, coagulation processes andoxidative stress and the inhibition of angiogenesis. Heat maps highlighted relationships betweenoxylipins and the cardiometabolic health parameters which were mainly lost in sarcopenic subjects.This exploratory study supports that targeted metabolomics of oxylipins could provide relevant andsubtle characterization of early disturbances associated with muscle-loss during aging

Muscle loss associated changes of oxylipin signatures during biological aging: an exploratory study from the PROOF cohort

Characterizations of the multiple mechanisms determining biological aging are required to betterunderstand the etiology and identify early biomarkers of sarcopenia. Oxylipins are a large family ofsignaling lipids involved in the regulation of various biological processes that become dysregulatedduring aging.To investigate whether comprehensive oxylipin profiling could provide an integrated and finecharacterisation of the early phases of sarcopenia, we performed a quantitative targetedmetabolomics of oxylipins in plasma of 81-year old subjects from the PROOF cohort with decreased(n=12), stable (n=16) or increased appendicular muscle mass (n=14).Multivariate and univariate analyses identified significant and concordant changes of oxylipin profilesaccording to the muscle status. Of note, 90% of the most discriminant oxylipins were derived fromEPA and DHA and were increased in the sarcopenic subjects. The oxylipins signatures of sarcopenicsubjects revealed subtle activation of inflammatory resolution pathways, coagulation processes andoxidative stress and the inhibition of angiogenesis. Heat maps highlighted relationships betweenoxylipins and the cardiometabolic health parameters which were mainly lost in sarcopenic subjects.This exploratory study supports that targeted metabolomics of oxylipins could provide relevant andsubtle characterization of early disturbances associated with muscle-loss during aging