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The technical difficulty of separating extracellular vesicles (EVs) from plasma proteins in human blood presents a significant hurdle in EV research, particularly during nano ultra-high-performance liquid chromatography-tandem mass spectrometric (UHPLC-MS/MS) analysis, where detecting "vesicular" proteins among abundant plasma proteins is challenging. Standardisation is a pressing issue in EV research, prompting collaborative global efforts to address it. While the MISEV guidelines offer valuable recommendations, unanswered questions remain, particularly regarding sample storage. We compared size exclusion chromatography (SEC) columns with pore sizes of 35 nm and 70 nm to identify fractions with minimal contaminating proteins and the highest concentration of small EVs (sEVs). Following column selection, we explored potential differences in the quality and quantity of sEVs isolated from platelet-free plasma (PFP) after long-term storage at -80 °C (>2.5 years) compared to freshly drawn blood. Our methodologically rigorous study indicates that prolonged storage, under correct storage and processing conditions, does not compromise sEV quality. Both columns effectively isolated vesicles, with the 70 nm column exhibiting a higher abundance of "vesicular" proteins. We propose a relatively rapid and moderately efficient protocol for obtaining a comparatively pure sEV fraction from plasma, facilitating sEV processing in clinical trials.
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Epigenetic clocks can measure aging and predict the incidence of diseases and mortality. Higher levels of physical fitness are associated with a slower aging process and a healthier lifespan. Microbiome alterations occur in various diseases and during the aging process, yet their relation to epigenetic clocks is not explored. To fill this gap, we collected metagenomic (from stool), epigenetic (from blood), and exercise-related data from physically active individuals and, by applying epigenetic clocks, we examined the relationship between gut flora, blood-based epigenetic age acceleration, and physical fitness. We revealed that an increased entropy in the gut microbiome of physically active middle-aged/old individuals is associated with accelerated epigenetic aging, decreased fitness, or impaired health status. We also observed that a slower epigenetic aging and higher fitness level can be linked to altered abundance of some bacterial species often linked to anti-inflammatory effects. Overall our data suggest that alterations in the microbiome can be associated with epigenetic age acceleration and physical fitness.
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Microbioma Gastrointestinal , Microbiota , Humanos , Persona de Mediana Edad , Microbioma Gastrointestinal/genética , Aptitud Física , Microbiota/genética , Aceleración , Envejecimiento/genética , Epigénesis Genética , Metilación de ADNRESUMEN
The role of Peroxisome proliferator-activated receptor-gamma coactivator alpha (PGC-1α) in fat metabolism is not well known. In this study, we compared the mechanisms of muscle-specific PGC-1α overexpression and exercise-related adaptation-dependent fat metabolism. PGC-1α trained (PGC-1α Ex) and wild-trained (wt-ex) mice were trained for 10 weeks, five times a week at 30 min per day with 60 percent of their maximal running capacity. The PGC-1α overexpressed animals exhibited higher levels of Fibronectin type III domain-containing protein 5 (FNDC5), 5' adenosine monophosphate-activated protein kinase alpha (AMPK-α), the mammalian target of rapamycin (mTOR), Sirtuin 1 (SIRT1), Lon protease homolog 1 (LONP1), citrate synthase (CS), succinate dehydrogenase complex flavoprotein subunit A (SDHA), Mitofusin-1 (Mfn1), endothelial nitric oxide synthase (eNOS), Hormone-sensitive lipase (HSL), adipose triglyceride lipase (ATGL), G protein-coupled receptor 41 (GPR41), and Phosphatidylcholine Cytidylyltransferase 2 (PCYT2), and lower levels of Sirtuin 3 (SIRT3) compared to wild-type animals. Exercise training increased the protein content levels of SIRT1, HSL, and ATGL in both the wt-ex and PGC-1α trained groups. PGC-1α has a complex role in cellular signaling, including the upregulation of lipid metabolism-associated proteins. Our data reveals that although exercise training mimics the effects of PGC-1α overexpression, it incorporates some PGC-1α-independent adaptive mechanisms in fat uptake and cell signaling.
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Músculo Esquelético , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma , Condicionamiento Físico Animal , Animales , Masculino , Ratones , Adaptación Fisiológica , Proteínas Quinasas Activadas por AMP/metabolismo , Fibronectinas , Metabolismo de los Lípidos , Ratones Endogámicos C57BL , Ratones Transgénicos , Músculo Esquelético/metabolismo , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma/metabolismo , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma/genética , Transducción de Señal , Sirtuina 1/metabolismo , Sirtuina 1/genéticaRESUMEN
DNAmPhenoAge, DNAmGrimAge, and the newly developed DNAmFitAge are DNA methylation (DNAm)-based biomarkers that reflect the individual aging process. Here, we examine the relationship between physical fitness and DNAm-based biomarkers in adults aged 33-88 with a wide range of physical fitness (including athletes with long-term training history). Higher levels of VO2max (ρ = 0.2, p = 6.4E - 4, r = 0.19, p = 1.2E - 3), Jumpmax (p = 0.11, p = 5.5E - 2, r = 0.13, p = 2.8E - 2), Gripmax (ρ = 0.17, p = 3.5E - 3, r = 0.16, p = 5.6E - 3), and HDL levels (ρ = 0.18, p = 1.95E - 3, r = 0.19, p = 1.1E - 3) are associated with better verbal short-term memory. In addition, verbal short-term memory is associated with decelerated aging assessed with the new DNAm biomarker FitAgeAcceleration (ρ: - 0.18, p = 0.0017). DNAmFitAge can distinguish high-fitness individuals from low/medium-fitness individuals better than existing DNAm biomarkers and estimates a younger biological age in the high-fit males and females (1.5 and 2.0 years younger, respectively). Our research shows that regular physical exercise contributes to observable physiological and methylation differences which are beneficial to the aging process. DNAmFitAge has now emerged as a new biological marker of quality of life.
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Metilación de ADN , Calidad de Vida , Masculino , Femenino , Humanos , Envejecimiento/genética , Ejercicio Físico , BiomarcadoresRESUMEN
The age-related decline in muscle function, particularly muscle power, is associated with increased risk of important clinical outcomes. Physical activity is an important determinant of muscle function, and different types of physical activity e.g. power-based versus endurance-based exercise appear to have differential effects on muscle power. Cross-sectional studies suggest that participation in power-based exercise is associated with greater muscle power across adulthood but this has not been investigated longitudinally. We recruited eighty-nine male and female power and endurance master athletes (sprint and distance runners respectively, baseline age 35-90y). Using jumping mechanography, we measured lower limb muscle function during a vertical jump including at least two testing sessions longitudinally over 4.5 ± 2.4y. We examined effects of time, discipline (power/endurance) and sex in addition to two- and three-way interactions using linear mixed-effects models. Peak relative power, relative force and jump height, but not Esslingen Fitness Index (indicating peak power relative to sex and age-matched reference data) declined with time. Peak power, force, height and EFI were greater in power than endurance athletes. There were no sex, discipline or sex*discipline interactions with time for any variable, suggesting that changes were similar over time for athletes of both sexes and disciplines. Advantages in lower limb muscle function in power athletes were maintained with time, in line with previous cross-sectional studies. These results suggest that improvements in lower limb function in less active older individuals following power-based training persist with continued adherence, although this requires further investigation in interventional studies.
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Envejecimiento , Radioisótopos de Itrio , Adulto , Anciano , Anciano de 80 o más Años , Atletas , Estudios Transversales , Femenino , Humanos , Estudios Longitudinales , Extremidad Inferior , Masculino , Persona de Mediana Edad , Músculos , Resistencia FísicaRESUMEN
Despite the intensive investigation of the molecular mechanism of skeletal muscle hypertrophy, the underlying signaling processes are not completely understood. Therefore, we used an overload model, in which the main synergist muscles (gastrocnemius, soleus) of the plantaris muscle were surgically removed, to cause a significant overload in the remaining plantaris muscle of 8-month-old Wistar male rats. SIRT1-associated pro-anabolic, pro-catabolic molecular signaling pathways, NAD and H2S levels of this overload-induced hypertrophy were studied. Fourteen days of overload resulted in a significant 43% (p < 0.01) increase in the mass of plantaris muscle compared to sham operated animals. Cystathionine-ß-synthase (CBS) activities and bioavailable H2S levels were not modified by overload. On the other hand, overload-induced hypertrophy of skeletal muscle was associated with increased SIRT1 (p < 0.01), Akt (p < 0.01), mTOR, S6 (p < 0.01) and suppressed sestrin 2 levels (p < 0.01), which are mostly responsible for anabolic signaling. Decreased FOXO1 and SIRT3 signaling (p < 0.01) suggest downregulation of protein breakdown and mitophagy. Decreased levels of NAD+, sestrin2, OGG1 (p < 0.01) indicate that the redox milieu of skeletal muscle after 14 days of overloading is reduced. The present investigation revealed novel cellular interactions that regulate anabolic and catabolic processes in the hypertrophy of skeletal muscle.
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Cistationina betasintasa/metabolismo , Proteínas Musculares/metabolismo , Músculo Esquelético/patología , Animales , Hipertrofia/genética , Hipertrofia/metabolismo , Hipertrofia/patología , Masculino , Proteínas Musculares/genética , Músculo Esquelético/metabolismo , Proteínas del Tejido Nervioso/antagonistas & inhibidores , Proteínas del Tejido Nervioso/genética , Proteínas del Tejido Nervioso/metabolismo , Proteínas Nucleares/antagonistas & inhibidores , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Proteínas Proto-Oncogénicas c-akt/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , Ratas , Ratas Wistar , Proteínas Quinasas S6 Ribosómicas/genética , Proteínas Quinasas S6 Ribosómicas/metabolismo , Sirtuina 1/genética , Sirtuina 1/metabolismo , Sirtuinas/antagonistas & inhibidores , Sirtuinas/genética , Sirtuinas/metabolismo , Serina-Treonina Quinasas TOR/genética , Serina-Treonina Quinasas TOR/metabolismoRESUMEN
The aging-related loss of muscle mass is thought to be partly attributable to motor neuron loss and motor unit remodeling that result in fiber type grouping. We examined fiber type grouping in 19- to 85-year-old athletes and non-athletes and evaluated to which extent any observed grouping is explained by the fiber type composition of the muscle. Since regular physical activity may stimulate reinnervation, we hypothesized that fiber groups are larger in master athletes than in age-matched non-athletes. Fiber type grouping was assessed in m. vastus lateralis biopsies from 22 young (19-27 years) and 35 healthy older (66-82 years) non-athletes, and 14 young (20-29 years), 51 middle-aged (38-65 years), and 31 older (66-85 years) athletes. An "enclosed fiber" was any muscle fiber of a particular type surrounded by fibers of the same type only. A fiber type group was defined as a group of fibers with at least one enclosed fiber. Only type II fiber cross-sectional area (FCSA) showed an age-related decline that was greater in athletes (P < .001) than in non-athletes (P = .012). There was no significant age-related effect on fiber group size or fiber group number in athletes or non-athletes, and the observed grouping was similar to that expected from the fiber type composition. At face value, these observations do 1) neither show evidence for an age-related loss and remodeling of motor units nor 2) improved reinnervation with regular physical activity, but 3) histological examination may not reveal the full extent of aging-related motor unit remodeling.
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Envejecimiento/fisiología , Fibras Musculares de Contracción Rápida/fisiología , Fibras Musculares de Contracción Lenta/fisiología , Deportes/fisiología , Adulto , Anciano , Anciano de 80 o más Años , Biopsia , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neuronas Motoras/fisiología , Fibras Musculares de Contracción Rápida/citología , Fibras Musculares de Contracción Lenta/citología , Músculo Cuádriceps/anatomía & histología , Músculo Cuádriceps/inervación , Músculo Cuádriceps/fisiología , Adulto JovenRESUMEN
We investigated longitudinal changes in tibia bone strength in master power (jumping and sprinting) and endurance (distance) athletes of both sexes. Bone mass but not cross-sectional moment of inertia was better maintained in power than endurance athletes over time, particularly in men and independent of changes in performance. OBJECTIVE: Assessment of effects of sex and athletic discipline (lower limb power events, e.g. sprint running and jumping versus endurance running events) on longitudinal changes in bone strength in masters athletes. METHODS: We examined tibia and fibula bone properties at distal (4% distal-proximal tibia length) and proximal (66% length) sites using peripheral quantitative computed tomography (pQCT) in seventy-one track and field masters athletes (30 male, 41 female, age at baseline 57.0 ± 12.2 years) in a longitudinal cohort study that included at least two testing sessions over a mean period of 4.2 ± 3.1 years. Effects of time, as well as time × sex and time × discipline interactions on bone parameters and calf muscle cross-sectional area (CSA), were examined. RESULTS: Effects of time were sex and discipline-dependent, even following adjustment for enrolment age, sex and changes in muscle CSA and athletic performance. Male sex and participation in power events was associated with better maintenance of tibia bone mineral content (BMC, an indicator of bone compressive strength) at 4% and 66% sites. In contrast, there was no strong evidence of sex or discipline effects on cross-sectional moment of inertia (CSMI, an indicator of bone bending and torsional strength-P > 0.3 for interactions). Similar sex and discipline-specific changes were also observed in the fibula. CONCLUSIONS: Results suggest that male athletes and those participating in lower limb power-based rather than endurance-based disciplines have better maintenance of bone compressive but not bending and torsional strength.
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Envejecimiento , Atletas , Densidad Ósea/fisiología , Huesos/fisiología , Carrera/fisiología , Adulto , Anciano , Anciano de 80 o más Años , Ejercicio Físico , Femenino , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , DeportesRESUMEN
According to our hypothesis, delayed onset muscle soreness (DOMS) is an acute compression axonopathy of the nerve endings in the muscle spindle. It is caused by the superposition of compression when repetitive eccentric contractions are executed under cognitive demand. The acute compression axonopathy could coincide with microinjury of the surrounding tissues and is enhanced by immune-mediated inflammation. DOMS is masked by sympathetic nervous system activity at initiation, but once it subsides, a safety mode comes into play to prevent further injury. DOMS becomes manifest when the microinjured non-nociceptive sensory fibers of the muscle spindle stop inhibiting the effects of the microinjured, hyperexcited nociceptive sensory fibers, therefore providing the 'open gate' in the dorsal horn to hyperalgesia. Reactive oxygen species and nitric oxide play a cross-talking role in the parallel, interlinked degeneration-regeneration mechanisms of these injured tissues. We propose that the mitochondrial electron transport chain generated free radical involvement in the acute compression axonopathy. 'Closed gate exercises' could be of nonpharmacological therapeutic importance, because they reduce neuropathic pain in addition to having an anti-inflammatory effect. Finally, DOMS could have an important ontogenetical role by not just enhancing ability to escape danger to survive in the wild, but also triggering muscle growth.
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Regular exercise induces a wide range of redox system-associated molecular adaptive responses to the nervous system. The intermittent induction of reactive oxygen species (ROS) during acute exercise sessions and the related upregulation of antioxidant/repair and housekeeping systems are associated with improved physiological function. Exercise-induced proliferation and differentiation of neuronal stem cells are ROS dependent processes. The increased production of brain derived neurotrophic factor (BDNF) and the regulation by regular exercise are dependent upon redox sensitive pathways. ROS are causative and associative factors of neurodegenerative diseases and regular exercise provides significant neuroprotective effects against Alzheimer's disease, Parkinson's disease, and hypoxia/reperfusion related disorders. Regular exercise regulates redox homeostasis in the brain with complex multi-level molecular pathways.
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Ejercicio Físico/fisiología , Enfermedades Neurodegenerativas/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Enfermedad de Alzheimer/metabolismo , Animales , Antioxidantes/metabolismo , Encéfalo/metabolismo , Lesiones Traumáticas del Encéfalo/metabolismo , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Homeostasis , Humanos , Hipoxia/metabolismo , Hipoxia-Isquemia Encefálica , Isquemia/metabolismo , Neuroprotección/fisiología , Oxidación-Reducción , Enfermedad de Parkinson/metabolismo , Accidente Cerebrovascular/metabolismoRESUMEN
Cellular energy demands are readily changed during physical exercise resulting in adaptive responses by signaling proteins of metabolic processes, including the NAD+ dependent lysine deacetylase SIRT1. Regular exercise results in systemic adaptation that restores the level of SIRT1 in the kidney, liver, and brain in patients with neurodegenerative diseases, and thereby normalizes cellular metabolic processes to attenuate the severity of these diseases. In skeletal muscle, over-expression of SIRT1 results in enhanced numbers of myonuclei improves the repair process after injury and is actively involved in muscle hypertrophy by up-regulating anabolic and downregulating catabolic processes. The present review discusses the different views of SIRT1 dependent deacetylation of PGC-α.
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Ejercicio Físico , Sirtuina 1 , Humanos , Músculo Esquelético , Sirtuina 1/genéticaRESUMEN
OBJECTIVE: The assessment of motor coordination is a very complex process and demonstrates a high degree of sport specificity. There are a limited number of tests, if any, where results correlate with the success rate of athletes in different sports. METHODS: Free style gymnastic exercise (FSGE) and coordination ball dribbling exercise (CBDE) were used to see whether the execution quality of these tests is related to the quality of athletes from team handball, water polo, kayak, rhythmical gymnastics (RG) and aerobics (222 athletes - 75 male, 147 female; 23 non-athletes - 9 male, 14 female). RESULTS: FSGE results related to the quality of performance in all sports (r = -0.232, p < 0.01 in handball, water polo, kayak and r = -0.26, p < 0.05 in aerobics and RG), while CBDE did not. Older players had higher ranking as they had more time to be successful at their sport (r = -0.498, p < 0.01 in handball, water polo, kayak; r = -0.298, p < 0.05 in aerobics and RG). The scores of FSGE were independent from the age and gender of the subjects. CONCLUSIONS: The main findings were: (i) that athletes did significantly better than the controls in both tests; (ii) RG and aerobics athletes did better on the FSGE than handball, water polo players and kayakers; (iii) handball players did better than kayakers, RG and aerobics athletes on the CBDE test; and (iv) better ranked athletes performed better on the FGSE test. Therefore, FSGE test appears to be a reliable test to assess coordination in variety of sport and different levels of sport performance.
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The decrease in cognitive/motor functions and physical abilities severely affects the aging population in carrying out daily activities. These disabilities become a burden on individuals, families and society in general. It is known that aging conditions are ameliorated with regular exercise, which attenuates the age-associated decline in maximal oxygen uptake (VO2max), production of reactive oxygen species (ROS), decreases in oxidative damage to molecules, and functional impairment in various organs. While benefits of physical exercise are well-documented, the molecular mechanisms responsible for functional improvement and increases in health span are not well understood. Recent findings imply that exercise training attenuates the age-related deterioration in the cellular housekeeping system, which includes the proteasome, Lon protease, autophagy, mitophagy, and DNA repair systems, which beneficially impacts multiple organ functions. Accumulating evidence suggests that exercise lessens the deleterious effects of aging. However, it seems unlikely that systemic effects are mediated through a specific biomarker. Rather, complex multifactorial mechanisms are involved to maintain homeostatic functions that tend to decline with age.
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Envejecimiento/fisiología , Ejercicio Físico/fisiología , Oxidación-Reducción , Anciano , Animales , Reparación del ADN , Genes Esenciales/genética , Homeostasis , Humanos , Especies Reactivas de Oxígeno/metabolismoRESUMEN
Regular physical exercise has health benefits and can prevent some of the ageing-associated muscle deteriorations. However, the biochemical mechanisms underlying this exercise benefit, especially in human tissues, are not well known. To investigate, we assessed this using miRNA profiling, mRNA and protein levels of anti-oxidant and metabolic proteins in the vastus lateralis muscle of master athletes aged over 65 years and age-matched controls. Master athletes had lower levels of miR-7, while mRNA or protein levels of SIRT3, SIRT1, SOD2, and FOXO1 levels were significantly higher in the vastus lateralis muscle of master athletes compared to muscles of age-matched controls. These results suggest that regular exercise results in better cellular metabolism and antioxidant capacity via maintaining physiological state of mitochondria and efficient ATP production and decreasing ageing-related inflammation as indicated by the lower level of miR-7 in master athletes.
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Ejercicio Físico , MicroARNs/genética , Músculo Esquelético/fisiología , Sirtuina 3/genética , Superóxido Dismutasa/genética , Regulación hacia Arriba , Anciano , Envejecimiento , Atletas , Regulación hacia Abajo , Femenino , Expresión Génica , Humanos , Masculino , Persona de Mediana Edad , ARN Mensajero/genética , Conducta Sedentaria , TranscriptomaRESUMEN
Reactive oxygen and nitrogen species (RONS) are important cellular regulators of key physiological processes in skeletal muscle. In this review, we explain how RONS regulate muscle contraction and signaling, and why they are important for membrane remodeling, protein turnover, gene expression, and epigenetic adaptation. We discuss how RONS regulate carbohydrate uptake and metabolism of skeletal muscle, and how they indirectly regulate fat metabolism through silent mating type information regulation 2 homolog 3 (SIRT3). RONS are causative/associative signaling molecules, which cause sarcopenia or muscle hypertrophy. Regular exercise influences redox biology, metabolism, and anabolic/catabolic pathways in skeletal muscle in an intensity dependent manner.
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KEY POINTS: Silent mating type information regulation 2 homologue 1 (SIRT1) activity and content increased significantly in overload-induced hypertrophy. SIRT1-mediated signalling through Akt, the endothelial nitric oxide synthase mediated pathway, regulates anabolic process in the hypertrophy of skeletal muscle. The regulation of catabolic signalling via forkhead box O 1 and protein ubiquitination is SIRT1 dependent. Overload-induced changes in microRNA levels regulate SIRT1 and insulin-like growth factor 1 signalling. ABSTRACT: Significant skeletal muscle mass guarantees functional wellbeing and is important for high level performance in many sports. Although the molecular mechanism for skeletal muscle hypertrophy has been well studied, it still is not completely understood. In the present study, we used a functional overload model to induce plantaris muscle hypertrophy by surgically removing the soleus and gastrocnemius muscles in rats. Two weeks of muscle ablation resulted in a 40% increase in muscle mass, which was associated with a significant increase in silent mating type information regulation 2 homologue 1 (SIRT1) content and activity (P < 0.001). SIRT1-regulated Akt, endothelial nitric oxide synthase and GLUT4 levels were also induced in hypertrophied muscles, and SIRT1 levels correlated with muscle mass, paired box protein 7 (Pax7), proliferating cell nuclear antigen (PCNA) and nicotinamide phosphoribosyltransferase (Nampt) levels. Alternatively, decreased forkhead box O 1 (FOXO1) and increased K48 polyubiquitination also suggest that SIRT1 could be involved in the catabolic process of hypertrophy. Furthermore, increased levels of K63 and muscle RING finger 2 (MuRF2) protein could also be important enhancers of muscle mass. We report here that the levels of miR1 and miR133a decrease in hypertrophy and negatively correlate with muscle mass, SIRT1 and Nampt levels. Our results reveal a strong correlation between SIRT1 levels and activity, SIRT1-regulated pathways and overload-induced hypertrophy. These findings, along with the well-known regulatory roles that SIRT1 plays in modulating both anabolic and catabolic pathways, allow us to propose the hypothesis that SIRT1 may actually play a crucial causal role in overload-induced hypertrophy of skeletal muscle. This hypothesis will now require rigorous direct and functional testing.
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Contracción Muscular , Músculo Esquelético/patología , Sirtuina 1/metabolismo , Animales , Citocinas/genética , Citocinas/metabolismo , Transportador de Glucosa de Tipo 4/genética , Transportador de Glucosa de Tipo 4/metabolismo , Hipertrofia , Masculino , MicroARNs/genética , Proteínas Musculares/genética , Proteínas Musculares/metabolismo , Músculo Esquelético/metabolismo , Músculo Esquelético/fisiología , Proteínas del Tejido Nervioso/genética , Proteínas del Tejido Nervioso/metabolismo , Nicotinamida Fosforribosiltransferasa/genética , Nicotinamida Fosforribosiltransferasa/metabolismo , Óxido Nítrico Sintasa de Tipo III/genética , Óxido Nítrico Sintasa de Tipo III/metabolismo , Factores de Transcripción Paired Box/genética , Factores de Transcripción Paired Box/metabolismo , Antígeno Nuclear de Célula en Proliferación/genética , Antígeno Nuclear de Célula en Proliferación/metabolismo , Proteínas Proto-Oncogénicas c-akt/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , Ratas , Ratas Wistar , Transducción de Señal , Sirtuina 1/genética , Proteínas de Motivos Tripartitos/genética , Proteínas de Motivos Tripartitos/metabolismo , Ubiquitina-Proteína Ligasas/genética , Ubiquitina-Proteína Ligasas/metabolismo , UbiquitinaciónRESUMEN
It is debated whether exercise-induced ROS production is obligatory to cause adaptive response. It is also claimed that antioxidant treatment could eliminate the adaptive response, which appears to be systemic and reportedly reduces the incidence of a wide range of diseases. Here we suggest that if the antioxidant treatment occurs before the physiological function-ROS dose-response curve reaches peak level, the antioxidants can attenuate function. On the other hand, if the antioxidant treatment takes place after the summit of the bell-shaped dose response curve, antioxidant treatment would have beneficial effects on function. We suggest that the effects of antioxidant treatment are dependent on the intensity of exercise, since the adaptive response, which is multi pathway dependent, is strongly influenced by exercise intensity. It is further suggested that levels of ROS concentration are associated with peak physiological function and can be extended by physical fitness level and this could be the basis for exercise pre-conditioning. Physical inactivity, aging or pathological disorders increase the sensitivity to oxidative stress by altering the bell-shaped dose response curve.
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Antioxidantes/farmacología , Ejercicio Físico/fisiología , Oxidantes/metabolismo , Hormesis , Humanos , Estrés Oxidativo/efectos de los fármacos , Aptitud Física , Especies Reactivas de Oxígeno/metabolismoRESUMEN
There is an increasing volume of data connecting capacity to respond to exercise training with quality of life and aging. In this study, we used a rat model in which animals were selectively bred for low and high gain in running distance to test t whether genetic segregation for trainability is associated with brain function and signaling processes in the hippocampus. Rats selected for low response (LRT) and high response training (HRT) were randomly divided into control or exercise group that trained five times a week for 30 min per day for three months at 70% VO2max. All four groups had similar running distance before training. With training, HRT rats showed significantly greater increases in VO2max and running distance than LRT rats (p < 0.05). On the reverse Morris Maze test HRT-trained rats outperformed HRT control ones. Significant difference was noted between LRT and HRT groups in redox milieu as assessed by levels of reactive oxygen species (ROS), carbonylation of proteins, nNOS and S-nitroso-cysteine. Moreover the silent information regulator 1 (SIRT1), brain-derived neurotrophic factor (BDNF), ratio of phospho and total cAMP-response element binding protein (CREB), and apoptotic index, also showed significant differences between LRT and HRT groups. These findings suggest that aerobic training responses are not localized to skeletal muscle, but differently involve signaling processes in the brain of LRT and HRT rats.
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Encéfalo/fisiología , Prueba de Esfuerzo/métodos , Condicionamiento Físico Animal/métodos , Condicionamiento Físico Animal/fisiología , Animales , Reacción de Prevención/fisiología , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Hipocampo/fisiología , Masculino , Aprendizaje por Laberinto/fisiología , Consumo de Oxígeno/fisiología , Ratas , Especies Reactivas de Oxígeno/metabolismoRESUMEN
Regular exercise has systemic beneficial effects, including the promotion of brain function. The adaptive response to regular exercise involves the up-regulation of the enzymatic antioxidant system and modulation of oxidative damage. Reactive oxygen species (ROS) are important regulators of cell signaling. Exercise, via intensity-dependent modulation of metabolism and/or directly activated ROS generating enzymes, regulates the cellular redox state of the brain. ROS are also involved in the self-renewal and differentiation of neuronal stem cells and the exercise-mediated neurogenesis could be partly associated with ROS production. Exercise has strong effects on the immune system and readily alters the production of cytokines. Certain cytokines, especially IL-6, IL-1, TNF-α, IL-18 and IFN gamma, are actively involved in the modulation of synaptic plasticity and neurogenesis. Cytokines can also contribute to ROS production. ROS-mediated alteration of lipids, protein, and DNA could directly affect brain function, while exercise modulates the accumulation of oxidative damage. Oxidative alteration of macromolecules can activate signaling processes, membrane remodeling, and gene transcription. The well known neuroprotective effects of exercise are partly due to redox-associated adaptation.
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Encéfalo/metabolismo , Ejercicio Físico/fisiología , Neuroprotección , Especies Reactivas de Oxígeno/metabolismo , Adaptación Fisiológica , Encéfalo/citología , Citocinas/metabolismo , Humanos , Neurogénesis , Transducción de SeñalRESUMEN
Aging results in significant loss of mass and function of the skeletal muscle, which negatively impacts the quality of life. In this study we investigated whether aerobic exercise training has the potential to alter anabolic and catabolic pathways in the skeletal muscle. Five and twenty eight month old rats were used in the study. Aging resulted in decreased levels of follistatin/mTOR/Akt/Erk activation and increased myostatin/Murf1/2, proteasome subunits, and protein ubiquitination levels. In addition, TNF-α, reactive oxygen species (ROS), p53, and Bax levels were increased while Bcl-2 levels were decreased in the skeletal muscle of aged rats. Six weeks of exercise training at 60% of VO2max reversed the age-associated activation of catabolic and apoptotic pathways and increased anabolic signaling. The results suggest that the age-associated loss of muscle mass and cachexia could be due to the orchestrated down-regulation of anabolic and up-regulation of catabolic and pro-apoptotic processes. These metabolic changes can be attenuated by exercise training.