Effects of submaximal and supramaximal accentuated eccentric loading on mass and function.

Introduction: Eccentric-overload (EO) resistance training emerges as an alternative to more optimally prescribe intensity relative to the force generation capabilities of the eccentric muscle contraction. Given the difficulties to individually prescribe absolute eccentric loads relative to each person's eccentric ability, setting the load relative to the concentric one-repetition maximum (1-RM) is the most used EO training approach. Therefore, we investigated the effects of submaximal and supramaximal (i.e., eccentric loads above 100% of 1-RM) accentuated eccentric training on changes in lean mass, anabolic hormonal responses and muscle function. Methods: Physically active university students (n = 27) were randomly assigned to two training groups. Participants in the training groups performed dominant leg isotonic training twice a week for 10 weeks (four sets of eight repetitions). Isotonic resistance was generated by an electric-motor device at two different percentages of 1-RM for the eccentric phase; 90% submaximal load, SUB group) and 120% (supramaximal load, SUPRA group). Concentric load was the same for both groups (30% of 1-RM). Changes in total thigh lean mass (TTLM), anabolic hormonal responses (growth hormone, IGF-1, IL-6, and total testosterone), unilateral leg-press 1-RM, maximal voluntary isometric contractions (MVIC), local muscle endurance (XRM), muscle power at 40 (PP40), 60 (PP60) and 80% (PP80) of the 1-RM, and unilateral vertical jump height before and after training were compared between groups. Results: After training, both SUB and SUPRA groups showed similar increases (p < 0.05) in MVIC (19.2% and 19.6%), XRM (53.8% and 23.8%), PP40 (16.2% and 15.7%), TTLM (2.5% and 4.2%), IGF-1 (10.0% and 14.1%) and IL-6 (58.6% and 28.6%). However, increases in 1-RM strength (16.3%) and unilateral vertical jump height (10.0%-13.4%) were observed for SUPRA only. Indeed, SUPRA was shown to be more favorable than SUB training for increasing 1-RM [ES = 0.77 (1.49-0.05)]. Unilateral muscle power at medium and high intensity (10.2% and 10.5%) also increased in SUB but without significant differences between groups. Discussion: Similar functional and structural effects were demonstrated after 10 weeks EO training with submaximal and supramaximal eccentric loads. Although supramaximal loading might be superior for increasing 1-RM, the use of this approach does not appear to be necessary in healthy, active individuals.

Resistance Training Modulates Reticulum Endoplasmic Stress, Independent of Oxidative and Inflammatory Responses, in Elderly People.

Aging is related to changes in the redox status, low-grade inflammation, and decreased endoplasmic reticulum unfolded protein response (UPR). Exercise has been shown to regulate the inflammatory response, balance redox homeostasis, and ameliorate the UPR. This work aimed to investigate the effects of resistance training on changes in the UPR, oxidative status, and inflammatory responses in peripheral blood mononuclear cells of elderly subjects. Thirty elderly subjects volunteered to participate in an 8-week resistance training program, and 11 youth subjects were included for basal assessments. Klotho, heat shock protein 60 (HSP60), oxidative marker expression (catalase, glutathione, lipid peroxidation, nuclear factor erythroid 2-related factor 2, protein carbonyls, reactive oxygen species, and superoxide dismutase 1 and 2), the IRE1 arm of UPR, and TLR4/TRAF6/pIRAK1 pathway activation were evaluated before and following training. No changes in the HSP60 and Klotho protein content, oxidative status markers, and TLR4/TRAF6/pIRAK1 pathway activation were found with exercise. However, an attenuation of the reduced pIRE1/IRE1 ratio was observed following training. Systems biology analysis showed that a low number of proteins (RPS27A, SYVN1, HSPA5, and XBP1) are associated with IRE1, where XBP1 and RPS27A are essential nodes according to the centrality analysis. Additionally, a gene ontology analysis confirms that endoplasmic reticulum stress is a key mechanism modulated by IRE1. These findings might partially support the modulatory effect of resistance training on the endoplasmic reticulum in the elderly.

Cross-education effects of unilateral accentuated eccentric isoinertial resistance training on lean mass and function.

PURPOSE: We investigated the effects of three different unilateral isoinertial resistance training protocols with eccentric overload on changes in lean mass and muscle function of trained (TL) and contralateral non-trained (NTL) legs. METHODS: Physically active university students were randomly assigned to one of three training groups or a control group (n = 10/group). Participants in the training groups performed dominant leg isoinertial squat training twice a week for 6 weeks (4 sets of 7 repetitions) using either an electric-motor device with an eccentric phase velocity of 100% (EM100) or 150% (EM150) of concentric phase velocity or a conventional flywheel device (FW) with the same relative inertial load. Changes in thigh lean mass, unilateral leg-press one-repetition maximum (1-RM), muscle power at 40-80% 1-RM, and unilateral vertical jump height before and after training were compared between the groups and between TL and NTL. RESULTS: No changes in any variable were found for the control group. In TL, all training groups showed similar increases (p < 0.05) in 1-RM strength (22.4-30.2%), lean tissue mass (2.5-5.8%), muscle power (8.8-21.7%), and vertical jump height (9.1-32.9%). In NTL, 1-RM strength increased 22.0-27.8% without significant differences between groups; however, increases in lean mass (p < 0.001) were observed for EM150 (3.5%) and FW (3.8%) only. Unilateral vertical jump height (6.0-32.9%) and muscle power (6.8-17.5%) also increased in NTL without significant differences between training groups. CONCLUSION: The three eccentric-overload resistance training modalities produced similar neuromuscular changes in both the trained and non-trained legs, suggesting that strong cross-education effects were induced by the eccentric-overload training.

Resistance Training Diminishes the Expression of Exosome CD63 Protein without Modification of Plasma miR-146a-5p and cfDNA in the Elderly.

Aging-associated inflammation is characterized by senescent cell-mediated secretion of high levels of inflammatory mediators, such as microRNA (miR)-146a. Moreover, a rise of circulating cell-free DNA (cfDNA) is also related to systemic inflammation and frailty in the elderly. Exosome-mediated cell-to-cell communication is fundamental in cellular senescence and aging. The plasma changes in exercise-promoted miR-146a-5p, cfDNA, and exosome release could be the key to facilitate intercellular communication and systemic adaptations to exercise in aging. Thirty-eight elderly subjects (28 trained and 10 controls) volunteered in an 8-week resistance training protocol. The levels of plasma miR-146a-5p, cfDNA, and exosome markers (CD9, CD14, CD63, CD81, Flotillin [Flot]-1, and VDAC1) were measured prior to and following training. Results showed no changes in plasma miR-146a-5p and cfDNA levels with training. The levels of exosome markers (Flot-1, CD9, and CD81) as well as exosome-carried proteins (CD14 and VDAC1) remained unchanged, whereas an attenuated CD63 response was found in the trained group compared to the controls. These findings might partially support the anti-inflammatory effect of resistance training in the elderly as evidenced by the diminishment of exosome CD63 protein expression, without modification of plasma miR-146a-5p and cfDNA.

The comparative measurement of body segment parameters using dual energy X-ray absorptiometry between sexes.

BACKGROUND: The study aimed to determine the proportion of the body segments in relation to the total body mass in healthy people, as well as analyze the composition of each segment and compare these results between sexes. METHODS: A total of 60 young adults (30 men and 30 women) were subjected to a full-body scan by dual energy X-rays absorptiometry (DXA) under standardized conditions. The regions of interest (ROI) were determined by a single trained evaluator. The body was divided into 16 segments to obtain values of total mass, lean mass (LM), fat mass, bone mineral content (BMC), lean mass percentage (%LM) and fat mass percentage (%FM) of each body segment represented by the 16 ROI. RESULTS: Men presented higher absolute mass in the upper limbs (Δ=32.87%; P<0.05). The proportion of the lower limbs (Δ=6.83%; P<0.05) and trunk (Δ=5.07%; P<0.05) of men is higher than women. In addition, males have more LM in the upper limbs (Δ=42.19%; P<0.05) and trunk (Δ=26.46%; P<0.001), and more BMC in the trunk (Δ=18.78%; P<0.05) and forearms (Δ=32.21%; P<0.05). They also present higher %LM (Δ=6.48%; P<0.001) and lower %FM (Δ=54.43%; P<0.001) than women in the forearms. CONCLUSIONS: The different body segments represent a different percentage of the total body mass in men than in women, as well as men present more LM and BMC in the trunk and upper limbs.

Exercise training modulates the gut microbiota profile and impairs inflammatory signaling pathways in obese children.

Childhood obesity has reached epidemic levels and is a serious health concern associated with metabolic syndrome, nonalcoholic fatty liver disease, and gut microbiota alterations. Physical exercise is known to counteract obesity progression and modulate the gut microbiota composition. This study aims to determine the effect of a 12-week strength and endurance combined training program on gut microbiota and inflammation in obese pediatric patients. Thirty-nine obese children were assigned randomly to the control or training group. Anthropometric and biochemical parameters, muscular strength, and inflammatory signaling pathways in mononuclear cells were evaluated. Bacterial composition and functionality were determined by massive sequencing and metabolomic analysis. Exercise reduced plasma glucose levels and increased dynamic strength in the upper and lower extremities compared with the obese control group. Metagenomic analysis revealed a bacterial composition associated with obesity, showing changes at the phylum, class, and genus levels. Exercise counteracted this profile, significantly reducing the Proteobacteria phylum and Gammaproteobacteria class. Moreover, physical activity tended to increase some genera, such as Blautia, Dialister, and Roseburia, leading to a microbiota profile similar to that of healthy children. Metabolomic analysis revealed changes in short-chain fatty acids, branched-chain amino acids, and several sugars in response to exercise, in correlation with a specific microbiota profile. Finally, the training protocol significantly inhibited the activation of the obesity-associated NLRP3 signaling pathway. Our data suggest the existence of an obesity-related deleterious microbiota profile that is positively modified by physical activity intervention. Exercise training could be considered an efficient nonpharmacological therapy, reducing inflammatory signaling pathways induced by obesity in children via microbiota modulation.

Comparison of the musculoskeletal effects of different iso-inertial resistance training modalities: Flywheel vs. electric-motor.

This study aimed to analyse whether increasing the eccentric overload (EO) during resistance training, in terms of range of motion and/or velocity using an electric-motor device, would induce different muscle adaptations than conventional flywheel-EO resistance training. Forty physically active university students (21.7 ± 3.4 years) were randomly placed into one of the three training groups (EX1, EX2, FW) and a control group without training (n = 10 per group). Participants in the training groups completed 12 sessions (4 sets of 7 repetitions) of iso-inertial single-leg squat training over 6 weeks for the dominant leg. Resistance was generated either by an electric-motor device at two different velocities for the eccentric phase; 100% (EX1) or 150% (EX2) of concentric speed, or by a conventional flywheel device (FW). Thigh lean tissue mass, unilateral leg press one-repetition maximum (1-RM), unilateral muscle power at different percentages of the 1-RM and bilateral/unilateral vertical jump were assessed before and after the 6-week training. There were significant (p < 0.05-0.001) main effects of time in the 3 training groups, indicating increased thigh lean tissue mass (2.5-5.8%), 1-RM load (22.4-30.2%), vertical jump performance (9.1-32.9%) and muscle power (8.8-21.7%), without differences across experimental groups. Participants in the control group did not improve any of the variables measured. In addition, EX2 showed greater gains in eccentric average peak power during training than EX1 and FW (p < 0.001). Despite the different EO offered, 6 weeks of resistance training using flywheel or electric-motor devices induced similar significant gains in muscle mass, strength, muscle power and vertical jump.

Effects of a resistance-training programme on endoplasmic reticulum unfolded protein response and mitochondrial functions in PBMCs from elderly subjects.

Aging has been related with a decline in the ability to handle protein folding, which leads to endoplasmic reticulum stress and alterations in unfolded protein response (UPR). Importantly, physical activity could activate the UPR and attenuate or prevent age-induced endoplasmic reticulum (ER) dysfunction. The current study evaluated the effects of a resistance exercise on UPR and mitochondrial functions in peripheral blood mononuclear cells (PBMCs) from elderly subjects. Thirty healthy women and men (age, 72.8, sx- = 2.2 years) were randomized to a training group, which performed an 8-week resistance training programme, or a control group, which followed their daily routines. The phosphorylation of PERK and IRE1, as well as ATF4, and XBP1 protein expression, significantly increased following the training, while expression of BiP, AFT6 and CHOP remain without changes. Additionally, the intervention also induced an increase in PGC-1α and Mfn1 protein levels, while no changes were found in Drp1 expression. Finally, the resistance protocol was not able to activate PINK1/Parkin and Bnip3/Nix pathways. The results obtained seem to indicate that 8-week resistance exercise activates the UPR, stimulates mitochondrial biogenesis, maintains mitochondrial dynamics and prevents mitophagy activation by unfolded proteins in PBMCs from elderly subjects.

Endoplasmic Reticulum Unfolded Protein Response, Aging and Exercise: An Update.

The endoplasmic reticulum (ER) is a dynamic and multifunctional organelle responsible for protein biosynthesis, folding, assembly and modifications. Loss of protein folding regulation, which leads to unfolded or misfolded proteins accumulation inside the ER lumen, drives ER stress (ERS) and unfolded protein response (UPR) activation. During aging, there is a decline in the ability of the cell to handle protein folding, accumulation and aggregation, and the function of UPR is compromised. There is a progressive failure of the chaperoning systems and a decline in many of its components, so that the UPR activation cannot rescue the ERS. Physical activity has been proposed as a powerful tool against aged-related diseases, which are linked to ERS. Interventional studies have demonstrated that regular exercise is able to decrease oxidative stress and inflammation and reverse mitochondrial and ER dysfunctions. Exercise-induced metabolic stress could activate the UPR since muscle contraction is directly involved in its activation, mediating exercise-induced adaptation responses. In fact, regular moderate-intensity exercise-induced ERS acts as a protective mechanism against current and future stressors. However, biological responses vary according to exercise intensity and therefore induce different degrees of ERS and UPR activation. This article reviews the effects of aging and exercise on ERS and UPR, also analyzing possible changes induced by different types of exercise in elderly subjects.

Mitochondrial Function and Mitophagy in the Elderly: Effects of Exercise.

Aging is a natural, multifactorial and multiorganic phenomenon wherein there are gradual physiological and pathological changes over time. Aging has been associated with a decrease of autophagy capacity and mitochondrial functions, such as biogenesis, dynamics, and mitophagy. These processes are essential for the maintenance of mitochondrial structural integrity and, therefore, for cell life, since mitochondrial dysfunction leads to an impairment of energy metabolism and increased production of reactive oxygen species, which consequently trigger mechanisms of cellular senescence and apoptotic cell death. Moreover, reduced mitochondrial function can contribute to age-associated disease phenotypes in model organisms and humans. Literature data show beneficial effects of exercise on the impairment of mitochondrial biogenesis and dynamics and on the decrease in the mitophagic capacity associated to aging. Thus, exercise could have effects on the major cell signaling pathways that are involved in the mitochondria quality and quantity control in the elderly. Although it is known that several exercise protocols are able to modify the activity and turnover of mitochondria, further studies are necessary in order to better identify the mechanisms of interaction between mitochondrial functions, aging, and physical activity, as well as to analyze possible factors influencing these processes.

Skeletal muscle functional and structural adaptations after eccentric overload flywheel resistance training: a systematic review and meta-analysis.

OBJECTIVES: The purpose of this meta-analysis was to examine the effect of flywheel (FW) resistance training with Eccentric Overload (FW-EOT) on muscle size and functional capacities (i.e. strength and power) in athletes and healthy subjects, and to compare FW-induced adaptations with those triggered by traditional resistance exercise interventions. DESIGN: A systematic review and meta-analysis of randomised controlled trials. METHODS: A search of electronic databases [PubMed, MEDLINE (SportDiscus), Web of Science, Scopus and PEDro] was conducted to identify all publications employing FW-EOT up to April 30, 2016. Outcomes were analyzed as continuous outcomes using a random effects model to calculate a standardized mean difference (SMD) and 95% CI. A total of 9 studies with 276 subjects and 92 effect sizes met the inclusion criteria and were included in the statistical analyses. RESULTS: The overall pooled estimate from the main effects analysis was 0.63 (95% CI 0.49-0.76) with a significant (p<0.001) Z overall effect of 9.17. No significant heterogeneity (p value=0.78) was found. The meta-analysis showed significant differences between FW-EOT vs. conventional resistance training in concentric and eccentric strength, muscle power, muscle hypertrophy, vertical jump height and running speed, favoring FW-EOT. CONCLUSIONS: This meta-analysis provides evidence supporting the superiority of FW-EOT, compared with traditional weight-stack exercise, to promote skeletal muscle adaptations in terms of strength, power and size in healthy subjects and athletes.

Impact of resistance training on the autophagy-inflammation-apoptosis crosstalk in elderly subjects.

Aging is associated with a decline in autophagy and a state of low-grade inflammation which further affects apoptosis and autophagy. Importantly, these alterations could reverse with regular physical activity. This study assessed the effects of a resistance exercise training program on autophagy, NLRP3 inflammasome, and apoptosis in peripheral blood mononuclear cells (PBMCs) from old subjects. Twenty-six healthy women and men (age, 69.6±1.5 yr) were randomized to a training (TG) or a control (CG) group. TG performed an 8-week resistance training program, while CG followed their daily routines. Protein expression of beclin-1, Atg12, Atg16 and LAMP-2 increased following the training program, while expression of p62/SQSTM1 and phosphorylation of ULK-1 at Ser757 were significantly lower. Resistance exercise also induced a decrease in NLRP3 expression and in the caspase-1/procaspase-1 ratio. Expression of Bcl-2 and Bcl-xL, as well as the Bad/BcL-2 ratio were reduced, and there was a significant decrease in the protein content of caspase-3. The results obtained seem to indicate that 8-week resistance training stimulates autophagy, prevents NLRP3 inflammasome activation, and reduces apoptosis in PBMCs from elderly subjects. These data could have a significant impact in prevention and rehabilitation programs currently employed in elderly population.

Functional and Muscle-Size Effects of Flywheel Resistance Training with Eccentric-Overload in Professional Handball Players.

The aim of the study was to analyse the effects of 6 week (15 sessions) flywheel resistance training with eccentric-overload (FRTEO) on different functional and anatomical variables in professional handball players. Twenty-nine athletes were recruited and randomly divided into two groups. The experimental group (EXP, n = 15) carried out 15 sessions of FRTEO in the leg-press exercise, with 4 sets of 7 repetitions at a maximum-concentric effort. The control group (CON, n = 14) performed the same number of training sessions including 4 sets of 7 maximum repetitions (7RM) using a weight-stack leg-press machine. The results which were measured included maximal dynamic strength (1RM), muscle power at different submaximal loads (PO), vertical jump height (CMJ and SJ), 20 m sprint time (20 m), T-test time (T-test), and Vastus-Lateralis muscle (VL) thickness. The results of the EXP group showed a substantially better improvement (p < 0.05-0.001) in PO, CMJ, 20 m, T-test and VL, compared to the CON group. Moreover, athletes from the EXP group showed significant improvements concerning all the variables measured: 1RM (ES = 0.72), PO (ES = 0.42 - 0.83), CMJ (ES = 0.61), SJ (ES = 0.54), 20 m (ES = 1.45), T-test (ES = 1.44), and VL (ES = 0.63 - 1.64). Since handball requires repeated short, explosive effort such as accelerations and decelerations during sprints with changes of direction, these results suggest that FRTEO affects functional and anatomical changes in a way which improves performance in well-trained professional handball players.

Impact of functional determinants on 5.5-year mortality in Amazon riparian elderly.

Objective To ascertain whether modifiable physical performance-based measurements predicted 5.5-year mortality in a riparian elderly cohort in the Amazon rainforest region. Methods A longitudinal study evaluating the impact of functional determinants on 5.5-year mortality in a riparian elderly cohort from Maués City in the state of Amazonas, Brazil, was performed. The study was a follow-up of a previous observational investigation that evaluated various fitness tests in 630 Amazonian riparian elderly (291 males and 339 females) aged 72.3 ± 8.0 (60-99) years old. The cohort was selected for its adverse environmental conditions, which increased the risk of falls yet required maintenance of good physical condition for carrying out relatively rigorous daily activities, and restricted access to specialized health services. Official death records were obtained from the Maués Municipal Health Department. Results A total of 80 study participants (12.7%) died over the 5.5-year study period. Kaplan-Meier regression analysis showed significant association between Timed Up and Go (TUG) test scores ≥ 14 seconds and mortality risk, independent of sex, age, and other health variables. Conclusions The study results suggest that the TUG test can be used as an indicator for initiating therapeutic and preventive actions, including conducting exercises or physical activities adapted to the health and functional conditions of the elderly, by identifying elderly people with a higher relative risk of mortality.

Impact of functional determinants on 5/5-year mortality in Amazon riparian elderly / Influencia de los determinantes de la capacidad funcional sobre la mortalidad a 5/5 años de los ancianos de las zonas ribereñas del Amazonas

ABSTRACT Objective To ascertain whether modifiable physical performance–based measurements predicted 5.5-year mortality in a riparian elderly cohort in the Amazon rainforest region. Methods A longitudinal study evaluating the impact of functional determinants on 5.5-year mortality in a riparian elderly cohort from Maués City in the state of Amazonas, Brazil, was performed. The study was a follow-up of a previous observational investigation that evaluated various fitness tests in 630 Amazonian riparian elderly (291 males and 339 females) aged 72.3 ± 8.0 (60–99) years old. The cohort was selected for its adverse environmental conditions, which increased the risk of falls yet required maintenance of good physical condition for carrying out relatively rigorous daily activities, and restricted access to specialized health services. Official death records were obtained from the Maués Municipal Health Department. Results A total of 80 study participants (12.7%) died over the 5.5-year study period. Kaplan-Meier regression analysis showed significant association between Timed Up and Go (TUG) test scores ≥ 14 seconds and mortality risk, independent of sex, age, and other health variables. Conclusions The study results suggest that the TUG test can be used as an indicator for initiating therapeutic and preventive actions, including conducting exercises or physical activities adapted to the health and functional conditions of the elderly, by identifying elderly people with a higher relative risk of mortality.

RESUMEN Objetivo Evaluar si los parámetros modificables del rendimiento físico permiten predecir la mortalidad a 5,5 años en una cohorte de ancianos de las zonas ribereñas de la selva tropical del Amazonas. Métodos En este estudio longitudinal se evaluó la influencia de los determinantes de la capacidad funcional sobre la mortalidad a 5,5 años en una cohorte de ancianos de la ciudad ribereña de Maués del estado de Amazonas (Brasil). El estudio consistió en un seguimiento de una investigación observacional anterior en la que se efectuaron diversas pruebas para determinar el estado físico de 630 ancianos de las zonas ribereñas del Amazonas (291 hombres y 339 mujeres) de 72,3 años de edad ± 8,0 (60-99) años. La cohorte fue seleccionada en función de las condiciones ambientales adversas, que aumentan el riesgo de caídas pero exigen un buen estado físico para llevar adelante las actividades relativamente rigurosas de la vida cotidiana, así como del acceso limitado a servicios de salud especializados. Los certificados de defunción oficiales se obtuvieron del Ministerio de Salud del Municipio de Maués. Resultados En el transcurso del estudio, que tuvo una duración de 5,5 años, fallecieron 80 participantes (12,7 %). El análisis de regresión de Kaplan-Meier reveló una relación significativa entre los valores de la prueba cronometrada de levantarse y caminar (TUG) ≥ 14 segundos y el riesgo de mortalidad, que fue independiente del sexo, la edad y demás variables de salud. Conclusiones Los resultados de este estudio indican que la prueba TUG puede emplearse como indicador de la necesidad de instituir medidas terapéuticas y preventivas, como ejercicios o actividades físicas adaptadas a la salud y el estado funcional de los ancianos, dado que permite detectar a aquellos que están expuestos a un riesgo relativo de muerte más alto.

Effects of aerobic training on markers of autophagy in the elderly.

Autophagy is a molecular process essential for the maintenance of cellular homeostasis, which appears to (i) decline with age and (ii) respond to physical exercise. In addition, recent evidence suggests a crosstalk between autophagy and toll-like receptor (TLR)-associated inflammatory responses. This study assessed the effects of aerobic exercise training on autophagy and TLR signaling in older subjects. Twenty-nine healthy women and men (age, 69.7 ± 1.0 year) were randomized to a training (TG) or a control (CG) group. TG performed an 8-week aerobic training program, while CG followed their daily routines. Peripheral blood mononuclear cells were isolated from blood samples obtained before and after the intervention, and protein levels of protein 1 light chain 3 (LC3), sequestosome 1 (p62/SQSTM1), beclin-1, phosphorylated unc-51-like kinase (ULK-1), ubiquitin-like autophagy-related (Atg)12, Atg16, and lysosome-associated membrane protein (LAMP)-2 were measured. TLR2 and TLR4 signaling pathways were also analyzed. Peak oxygen uptake increased in TG after the intervention. Protein expression of beclin-1, Atg12, Atg16, and the LC3II/I ratio increased following the training program (p < 0.05), while expression of p62/SQSTM1 and phosphorylation of ULK-1 at Ser(757) were lower (p < 0.05). Protein content of TLR2, TLR4, myeloid differentiation primary response gen 88 (MyD88), and TIR domain-containing adaptor-inducing interferon (TRIF) were not significantly modified by exercise. The current data indicate that aerobic exercise training induces alterations in multiple markers of autophagy, which seem to be unrelated to changes in TLR2 and TLR4 signaling pathways. These results expand knowledge on exercise-induced autophagy adaptations in humans and suggest that the exercise type employed may be a key factor explaining the potential relationship between autophagy and TLR pathways.

Whole-body vibration improves the anti-inflammatory status in elderly subjects through toll-like receptor 2 and 4 signaling pathways.

Regular physical exercise has anti-inflammatory effects in elderly subjects. Yet, the inflammatory responses after whole body vibration (WBV) training, a popular exercise paradigm for the elderly, remain to be elucidated. This study assessed the effects of WBV training on the inflammatory response associated with toll-like receptors (TLRs) signaling pathways. Twenty-eight subjects were randomized to a training group (TG) or a control group (CG). TG followed an 8-week WBV training program. Blood samples were obtained before and after the training period in both groups. Peripheral blood mononuclear cells were isolated, and mRNA and protein levels of makers involved in the TLR2/TLR4 myeloid differentiation primary response gen 88 (MyD88) and TIR domain-containing adaptor inducing interferon (TRIF)-dependent pathways were analyzed. Plasma TNFα and C-reactive protein levels were also assessed. The WBV program reduced protein expression of TLR2, TLR4, MyD88, p65, TRIF and heat shock protein (HSP) 60, while HSP70 content increased. IL-10 mRNA level and protein concentration were upregulated, and TNFα protein content decreased, after WBV training. Plasma concentration of C-reactive protein and TNFα decreased in the TG. The current data suggest WBV may improve the anti-inflammatory status of elderly subjects through an attenuation of MyD88- and TRIF-dependent TLRs signaling pathways.

Role of Toll-like receptor 2 and 4 signaling pathways on the inflammatory response to resistance training in elderly subjects.

This study assessed the effects of a resistance exercise training program on the inflammatory response associated with Toll-like receptor (TLR) 2 and TLR4 signaling pathways in senior participants. Twenty-six healthy subjects (age, 69.5 ± 1.3) were randomized to a training (TG; n = 16) or a control (CG; n = 10) group. TG performed an 8-week resistance training program, while CG followed their daily routines. Peripheral blood mononuclear cells were isolated from blood samples obtained before and after the intervention, and levels of proteins involved in the TLR2, TLR4, and myeloid differentiation primary response gene 88 (MyD88)-dependent and MyD88-independent pathways were analyzed. The inflammatory status was evaluated through messenger RNA (mRNA) and protein content of interleukin (IL)-10 and tumor necrosis factor alpha (TNF-α) and plasma levels of C-reactive protein (CRP). After the 8-week resistance training, TLR2 and TLR4 protein expression was reduced in TG. MyD88, p65, phospho-p38, TIR domain-containing adaptor inducing interferon (TRIF), IKKi/IKKε, phospho-interferon regulatory factor (IRF) 3, and phosho-IRF7 were also downregulated in TG after the intervention. The training program induced an increase of phospho-extracellular signal-regulated kinases 1 and 2 (ERK1/2) and Hsp70 and a reduction of Hsp60. While TNF-α mRNA and protein values remained unchanged in both TG and CG, IL-10 mRNA and protein content were upregulated in TG after the intervention. CRP values decreased in TG only. The increase in Hsp70 negatively correlated with TLR2 and TLR4 downregulation. These data suggest that resistance exercise may represent an effective tool to ameliorate the pro-inflammatory status of old participants through an attenuation of MyD88-dependent and MyD88-independent TLR2 and TLR4 signaling pathways.