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Although unfolded protein response (UPR) is essential for cellular protection, its prolonged activation may induce apoptosis, compromising cellular longevity. The aging process increases the endoplasmic reticulum (ER) stress in skeletal muscle. However, whether combined exercise can prevent age-induced ER stress in skeletal muscle remains unknown. Evidence suggests that ER stress may increase inflammation by counteracting the positive effects of interleukin-10 (IL-10), whereas its administration in cells inhibits ER stress and apoptosis. This study verified the effects of aging and combined exercise on physical performance, ER stress markers, and inflammation in the quadriceps of mice. Moreover, we verified the effects of IL-10 on ER stress markers. C57BL/6 mice were distributed into young (Y, 6 mo old), old sedentary (OS, sedentary, 24 mo old), and old trained group (OT, submitted to short-term combined exercise, 24 mo old). To clarify the role of IL-10 in UPR pathways, knockout mice lacking IL-10 were used. The OS mice presented worse physical performance and higher ER stress-related proteins, such as C/EBP homologous protein (CHOP) and phospho-eukaryotic translation initiation factor 2 alpha (p-eIF2α/eIF2α). The exercise protocol increased muscle strength and IL-10 protein levels in OT while inducing the downregulation of CHOP protein levels compared with OS. Furthermore, mice lacking IL-10 increased BiP, CHOP, and p-eIF2α/eIF2α protein levels, indicating this cytokine can regulate the ER stress response in skeletal muscle. Bioinformatics analysis showed that endurance and resistance training downregulated DNA damage inducible transcript 3 (DDIT3) and XBP1 gene expression in the vastus lateralis of older people, reinforcing our findings. Thus, combined exercise is a potential therapeutic intervention for promoting adjustments in ER stress markers in aged skeletal muscle.NEW & NOTEWORTHY Aging elevates endoplasmic reticulum (ER) stress in skeletal muscle, potentially heightening inflammation by opposing interleukin-10 (IL-10) effects. This study found that short-term combined exercise boosted strength and IL-10 protein levels while reducing CHOP protein levels in older mice. In addition, IL-10-deficient mice exhibited increased ER stress markers, highlighting IL-10's role in regulating ER stress in skeletal muscle. Consequently, combined exercise emerges as a therapeutic intervention to elevate IL-10 and adjust ER stress markers in aging.

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Evidence indicates that master athletes have higher concentration of Sirtuin 1 (Sirt1), lower body fat (BF), and greater activity of the hypothalamic-pituitary-gonadal axis in comparison to untrained peers. However, no published data have demonstrated possible mediation effect of Sirt1 in the interaction of BF and testosterone in this population. Therefore, this study compared and verified possible associations between Sirt1, BF, fat mass index (FMI), testosterone, luteinizing hormone (LH), and testosterone/luteinizing hormone (T/LH) ratio in middle-aged master athletes (n = 54; 51.22 ± 7.76 years) and control middle-aged peers (n = 21; 47.76 ± 8.47 years). Venous blood was collected for testosterone, LH, and Sirt1. BF was assessed through skinfold protocol. Although LH concentration did not differ between groups, master athletes presented higher concentration of Sirt1, testosterone, and T/LH ratio, and lower BF and FMI in relation to age-matched nonathletes. Moreover, Sirt1 correlated positively with testosterone and T/LH ratio, negatively with BF, and was not significantly correlated with LH (mediation analysis revealed the effect of BF on testosterone is mediated by Sirt1 and vice versa; R2 = .1776; p = .032). In conclusion, master athletes have higher testosterone, T/LH ratio, and Sirt1, and lower BF and FMI in relation to untrained peers. Furthermore, Sirt1 was negatively associated with BF and positively associated with testosterone and T/LH ratio. These findings suggest that increased circulating Sirt1, possibly due to the master athlete's training regimens and lifestyle, exhibits a potential mediation effect on the interaction between endocrine function and body composition.

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Different lifestyle changes have been employed to improve clinical hypertension. However, there is scarce evidence on the blood pressure responsiveness to resistance training (RT) in hypertensive older adults. Consequently, little is known about some participants clinically reducing blood pressure and others not. Thus, we investigate the effects and responsiveness of RT on blood pressure in hypertensive older adults. We secondarily evaluated the biochemical risk factors for cardiovascular disease and functional performance. Older participants with hypertension were randomly assigned into RT (n = 27) and control group (n = 25). Blood pressure, functional performance (timed up and go, handgrip strength, biceps curl and sit-to-stand), fasting glucose, and lipid profiles were evaluated preintervention and postintervention. The statistic was performed in a single-blind manner, the statistician did not know who was the control and RT. RT was effective in reducing systolic blood pressure (SBP) (pre 135.7 ±â€…14.7; post 124.7 ±â€…11.0; P  < 0.001) and the responses to RT stimuli varied noticeably between hypertensive older adults after 12 weeks. For example, 13 and 1 responders displayed a minimal clinical important difference for SBP attenuation (10.9 mmHg) in the RT and control groups, respectively. RT improved the functional performance of older people with hypertension, while no differences were found in biochemical parameters (triglycerides, HDL, LDL, fasting glucose) after 12 weeks. In conclusion, responses to RT stimuli varied noticeably between hypertensive individuals and RT was effective in reducing SBP.

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Purpose: To propose predictive models for absolute muscle strength (AMS) of elderly people with type 2 Diabetes Mellitus (DM2) in primary health care. Patients and Methods: The cross-sectional study was conducted with 138 elderly diabetics. The AMS was measured by a JAMAR® hydraulic handgrip dynamometer, determined by the sum of both hands. The following indices were evaluated: waist-to-height ratio (WHtR), body mass index (BMI), Lipid Accumulation Product (LAP), Triglyceride/High Density Lipoprotein (TG/HDL) ratio and platelet/lymphocyte ratio (PLR). Multiple linear regression was used in the statistical analysis. Results: The final regression model indicated 66.4% (R²=0.66) of the variation in AMS. WHtR decreased AMS by 41.1% (ß = -0.19; t = -3.70; p < 0.001), while PLR by 11.3% (ß = -0.12; t = -2.36; p = 0.020). Male sex increased AMS by 10.6% (ß = 0.32; t = 4.16; p < 0.001), and lean mass (LM) by 0.89% (ß = 0.46; t = 6.03; p < 0.001). Conclusion: WHtR and PLR predicted a decrease, while male sex and LM predicted an increase in AMS. It is suggested that these markers be used as screening measures for variation in AMS in older adults with DM2. These results have relevant practical application in primary health care since the markers are easy to use.

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MMPs are enzymes involved in SARS-CoV-2 pathogenesis. Notably, the proteolytic activation of MMPs can occur through angiotensin II, immune cells, cytokines, and pro-oxidant agents. However, comprehensive information regarding the impact of MMPs in the different physiological systems with disease progression is not fully understood. In the current study, we review the recent biological advances in understanding the function of MMPs and examine time-course changes in MMPs during COVID-19. In addition, we explore the interplay between pre-existing comorbidities, disease severity, and MMPs. The reviewed studies showed increases in different MMP classes in the cerebrospinal fluid, lung, myocardium, peripheral blood cells, serum, and plasma in patients with COVID-19 compared to non-infected individuals. Individuals with arthritis, obesity, diabetes, hypertension, autoimmune diseases, and cancer had higher MMP levels when infected. Furthermore, this up-regulation may be associated with disease severity and the hospitalization period. Clarifying the molecular pathways and specific mechanisms that mediate MMP activity is important in developing optimized interventions to improve health and clinical outcomes during COVID-19. Furthermore, better knowledge of MMPs will likely provide possible pharmacological and non-pharmacological interventions. This relevant topic might add new concepts and implications for public health in the near future.

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BACKGROUND: The muscle performance is associated with several health outcomes in adults, however modifiable and non-modifiable risk factors in octogenarians have not yet been fully investigated. The aim of this study was to analyze the potential risk factors that negatively affect muscle strength in octogenarians. METHODS: This observational, descriptive, cross-sectional study included 87 older adult participants (56 women and 31 men) attending a geriatric clinic. General anthropometrics, health history, and body composition data were collected. Muscle strength was assessed by handgrip strength (HGS), appendicular skeletal muscle mass (ASMM) and the percentage of body fat were identified by Dual Energy X-ray Absorptiometry, and muscle quality index (MQI) was defined as the ratio of HGS by upper limbs ASMM. Multiple linear regression was conducted to determine predictive factors of the muscle strength. RESULTS: Females had lower HGS (1.39 kg) than male participants (p = 0.034). An increase of one unit MQI was associated with an increase of 3.38 kg in the HGS (p = 0.001). Each additional year of age was associated with a decrease of 0.12 kg in the HGS (p = 0.047). Regarding ASMM, an increase of one unit was associated with an increase of 0.98 kg in the HGS (p = 0.001). There was no association between dynapenia, body fat percentage, diseases and polypharmacy (p > 0.05). CONCLUSION: The gender, age, MQI, and ASMM influenced muscle strength of octogenarians. These intrinsic and extrinsic factors are relevant to improve our understanding of age-related complications and outline treatment guidance by healthcare professionals.

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BACKGROUND: the study determined the validity and reliability of measurements obtained using the portable traction dynamometer (PTD) (E-Lastic, E-Sports Solutions, Brazil) and the reproducibility between evaluators (precision) in the evaluation of the isometric muscle strength of the knee extensors of healthy male adults, compared to measurements obtained with the "gold standard" computerized dynamometer (CD) (Biodex System 3, Nova York, NY, USA). METHODS: we evaluated sixteen recreationally active men (29.50 ± 7.26 years). The test-retest reliability of both equipment to determine quadriceps strength, agreement analysis, and the minimal important difference were verified. RESULTS: excellent test-retest interrater reliability was observed for absolute and relative measurements, with a low absolute error for both sets of equipment and excellent validity of the PTD against the CD, as verified by linear regression and Pearson's correlation coefficient. CONCLUSIONS: PTD is a valid and reliable instrument for assessing the isometric strength of knee extensors, with results similar to the isometric CD "gold standard".

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The mechanisms of autophagy have been related to Alzheimer's disease (AD) pathogenesis by the endosomal-lysosomal system, having a critical function in forming amyloid-ß (Aß) plaques. Nevertheless, the exact mechanisms mediating disease pathogenesis remain unclear. The transcription factor EB (TFEB), a primary transcriptional autophagy regulator, improves gene expression, mediating lysosome function, autophagic flux, and autophagosome biogenesis. In this review, we present for the first time the hypothesis of how TFEB, autophagy, and mitochondrial function are interconnected in AD, providing a logical foundation for unraveling the critical role of chronic physical exercise in this process. Aerobic exercise training promotes Adiponectin Receptor 1 (AdipoR1)/AMP-activated protein kinase (AMPK)/TFEB axis activation in the brain of the AD animal model, which contributes to alleviated Aß deposition and neuronal apoptosis while improving cognitive function. Moreover, TFEB upregulates Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) and nuclear factor erythroid 2-related factor 2 (NRF-2), improving mitochondrial biogenesis and redox status. In addition, tissue contraction activates calcineurin in skeletal muscle, which induces TFEB nuclear translocation, raising the hypothesis that the same would occur in the brain. Thus, a deep and comprehensive exploration of the TFEB could provide new directions and strategies for preventing AD. We conclude that chronic exercise can be an effective TFEB activator, inducing autophagy and mitochondrial biogenesis, representing a potential nonpharmacological strategy contributing to brain health.

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Background: Low-frequency electrical stimulation (LFES) is an adjuvant method for heart failure (HF) patients with restrictions to start an exercise. However, the impact on molecular changes in circulating is unknown. We investigated the effects of 10 weeks of home-based LFES on plasma cytokines profile, redox biomarkers, metalloproteinases (MMPs) activity, and exercise performance in HF patients. Methods: Twenty-four HF patients (52.45 ± 9.15 years) with reduced ejection fraction (HFrEF) (EF < 40%), were randomly assigned to a home-based LFES or sham protocol. Plasma cytokines profile was assessed through interleukins, interferon-gamma, and tumor necrosis factor levels. Oxidative stress was evaluated through ferric reducing antioxidant power, thiobarbituric acid-reactive substances, and inducible nitric oxide synthase. The MMPs activity were analyzed by zymography. Cardiorespiratory capacity and muscle strength were evaluated by cardiopulmonary test and isokinetic. Results: LFES was able to increase the active-MMP2 activity post compared to pre-training (0.057 to 0.163, p = 0.0001), while it decreased the active-MMP9 (0.135 to 0.093, p = 0.02). However, it did not elicit changes in cytokines, redox biomarkers, or exercise performance (p > 0.05). Conclusion: LFES protocol is a promising intervention to modulate MMPs activity in HFrEF patients, although with limited functional effects. These preliminary responses may help the muscle to adapt to future mechanical demands dynamically.

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The establishment of fatigue following the acute exercise stimulus is a complex and multi-factorial process, that might arise due to a range of distinct physiological mechanisms. However, a practical method of assessing CrossFit® athletes' recovery status has been neglected entirely in real-world sporting practice. The study describes the acute and delayed time course of recovery following the CrossFit® Benchmark Workout Karen. Eight trained men (28.4 ± 6.4 years; 1RM back squat 139.1 ± 26.0 kg) undertook the Karen protocol. The protocol consists of 150 Wall Balls (9 kg), aiming to hit a target 3 m high. Countermovement jump height (CMJ), creatine kinase (CK), and perceived recovery status scale (PRS) (general, lower and upper limbs) were assessed pre, post-0h, 24, 48 and 72 h after the session. The creatine kinase concentration 24 h after was higher than pre-exercise (338.4 U/L vs. 143.3 U/L; p = 0.040). At 48h and 72 h following exercise, CK concentration had returned to baseline levels (p > 0.05). The general, lower and upper limbs PRS scores were lower in the 24-h post-exercise compared to pre-exercise (general PRS: 4.7 ± 1.5 and 7.7 ± 1.7; p = 0.013; upper limbs PRS: 6.6 ± 1.3 and 7.5 ± 1.3; p = 0.037; lower limbs PRS: 3.9 ± 2.5 and 7.3 ± 0.1; p = 0.046). Our findings provide insights into the fatigue profile and recovery in acute CrossFit® and can be useful to coaches and practitioners when planning training programs. Moreover, recovery status can be useful to optimize training monitoring and to minimize the potential detrimental effects associated with the performance of repeated high-intensity sessions of CrossFit®.

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Neuromuscular electrical stimulation (NMES) has been used to increase muscle strength and physical function. However, NMES induces rapid fatigue, limiting its application. To date, the effect of quadriceps femoris (QF) muscle length by knee and hip joint manipulation on NMES-induced contraction fatigability is not clear. We aimed to quantify the effects of different muscle lengths on NMES-induced contraction fatigability, fatigue index, and electromyographic (EMG) activity for QF muscle. QF maximum evoked contraction (QMEC) was applied in a 26 min protocol (10 s on; 120 s off; 12 contractions) in 20 healthy participants (24.0 ± 4.6 years old), over 4 sessions on different days to test different conditions. The tested conditions were as follows: supine with knee flexion of 60° (SUP60), seated with knee flexion of 60° (SIT60), supine with knee flexion of 20° (SUP20), and seated with knee flexion of 20° (SIT20). Contraction fatigability (torque decline assessed by maximal voluntary contraction [MVC] and during NMES), fatigue index (percentage reduction in MVC), and EMG activity (root mean square [RMS] and median frequency) of the superficial QF' constituents were assessed. After NMES, all positions except SUP20 had an absolute reduction in MVC (p < .001). Fatigue index was greater in SIT20 than in SIT60 (p < .001) and SUP20 (p = .01). There was significant torque reduction across the 12 QMEC in SUP60 and SIT60, up to 10.5% (p < .001-.005) and 9.49% (p < .001-.033), respectively. There was no torque reduction during NMES in SUP20 and SIT20. Fatigue was accompanied by an increase in RMS (p = .032) and a decrease in median frequency for SUP60 (p < .001). Median frequency increased only in the SUP20 condition (p = .021). We concluded that QF NMES-induced contraction fatigability is greater when the knee is flexed at 60° compared to 20°. In addition, a supine position promotes earlier fatigue for a 60° knee flexion, but it delays fatigue onset for a 20° knee flexion compared to the seated position. These results provide a rationale for lower limb positioning during NMES, which depends on training objectives, e.g., strengthening or task-specific functionality training.

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BACKGROUND: There are extensive studies focusing on non-invasive modalities to recover physiological systems after exercise-induced muscle damage (EIMD). Whole-body cryotherapy (WBC) and Partial-body cryotherapy (PBC) have been recommended for recovery after EIMD. However, to date, no systematic reviews have been performed to compare their effects on muscle performance and muscle recovery markers. METHODS: This systematic review with metanalysis compared the effects of WBC and PBC on muscle performance, muscle soreness (DOMS), and markers of muscular damage following EIMD. We used Pubmed, Embase, PEDro, and Cochrane Central Register of Controlled Trials as data sources. Two independent reviewers verified the methodological quality of the studies. The studies were selected if they used WBC and PBC modalities as treatment and included muscle performance and muscle soreness (DOMS) as the primary outcomes. Secondary outcomes were creatine kinase and heart rate variability. RESULTS: Six studies with a pooled sample of 120 patients were included. The methodological quality of the studies was moderate, with an average of 4.3 on a 0-10 scale (PEDro). RESULTS: Both cryotherapy modalities induce similar effects without difference between them. CONCLUSION: WBC and PBC modalities have similar global responses on muscle performance, soreness, and markers of muscle damage.

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Peripheral nerve injuries are cause of sensory disturbances and in functional abilities, and are associated personal and social costs. Strategies that maximize nerve regeneration and functional recovery are necessary, the exercise is an option. This study evaluated the effects of forced swimming exercise on neuromuscular histomorphometry and on functional recovery in a median nerve crush model. Sixteen Wistar rats underwent median nerve crush and were divided into control group (CG) and swimming group (SG). The forced swimming protocol started one week after the injury and was performed for 1 hr a day, 5 days per week, for 2 weeks. The rats swam with an overload of 5% and 10% of body weight in the first and second week, respectively. The functional recovery was assessed in three moments using the grasping test. On day 21, fragments of the median nerve and of the forearm flexors muscles were removed for histomorphometric analysis. The SG had functional recovery impaired (P<0.001) and presented lower myelinated fibers number, fiber and axon minimal diameter, myelin thickness and g-ratio in the proximal e distal segments of the median nerve (P<0.005) and area muscle fiber (P<0.005) than CG. Also, the SG presented a number of capillaries in the proximal segments of the median nerve greater than CG (P<0.005). The exercise protocol used in this study impaired the regeneration of the median nerve and negatively influenced the functional recovery.

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Aging is a natural process of organism deterioration, which possibly impairs multiple physiological functions. These harmful effects are linked to an accumulation of somatic mutations, oxidative stress, low-grade inflammation, protein damage, and mitochondrial dysfunction. It is known that these factors are capable of inducing telomere shortening, as well as intestinal dysbiosis. Otherwise, among the biological mechanisms triggered by physical exercise, the attenuation of pro-inflammatory mediators accompanied by redox state improvement can be the main mediators for microbiota homeostasis and telomere wear prevention. Thus, this review highlights how oxidative stress, inflammation, telomere attrition, and gut microbiota (GM) dysbiosis are interconnected. Above all, we provide a logical foundation for unraveling the role of physical exercise in this process. Based on the studies summarized in this article, exercise training can increase the biodiversity of beneficial microbial species, decrease low-grade inflammation and improve oxidative metabolism, these factors together possibly reduce telomeric shortening.

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Combining blood flow restriction (BFR) with exercise is considered a relevant, helpful method in load-compromised individuals and a viable replacement for traditional heavy-load strength training. BFR exercise may be particularly useful for those unable to withstand high mechanical stresses on joints resulting in skeletal muscle dysfunction, such as patients with chronic kidney disease (CKD). Current literature suggests that BFR training displays similar positive health benefits to exercise training alone for CKD patients, including maintenance of muscle strength, glomerular filtration rate maintenance, uremic parameters, inflammatory profile, redox status, glucose homeostasis, blood pressure adjustments, and low adverse reports. In this review of nine studies in CKD patients, we clarify the potential safety and health effects of exercise training with BFR compared to exercise training alone and recommend insights for future research and practical use. Furthermore, we introduce relevant gaps in this emerging field, providing substantial guidance, critical discussion, and valuable preliminary conclusions in this demographic of patients. However, based on the limited studies in this area, more research is necessary to determine the optimal BFR exercise programming.

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The extracellular matrix (ECM) is a 3-dimensional network of molecules that play a central role in differentiation, migration, and survival for maintaining normal homeostasis. It seems that ECM remodeling is required for adipose tissue expansion. Despite evidence indicating that ECM is an essential component of tissue physiology, adipose tissue ECM has received limited attention. Hence, there is great interest in approaches to neutralize the harmful effects of ECM enlargement. This review compiles and discusses the current literature on adipose tissue ECM remodeling in response to different dietary patterns and exercise training. High-calorie diets result in substantial adipose tissue ECM remodeling, which in turn could lead to fibrosis (excess deposition of collagens, elastin, and fibronectin), inflammation, and the onset of metabolic dysfunction. However, combining a nutritionally balanced diet with exercise is a remarkable potential strategy for lipolytic activity, preventing rapid ECM expansion in different adipose tissue depots. Despite the distinct exercise modalities (aerobic or resistance exercise) reversing adipose tissue fibrosis in animal models, the beneficial effect on humans remains controversial. Defining molecular pathways and specific mechanisms that mediate the positive effects on adipose tissue, ECM is essential in developing optimized interventions to improve health and clinical outcomes.

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This study aimed to evaluate the time course and responsiveness of plasma interleukin-6 (IL-6) and creatine kinase (CK) levels following acute eccentric resistance exercise in sedentary obese older women with a different muscle quality index (MQI). Eighty-eight participants (69.4 ± 6.06 years) completed an acute eccentric resistance exercise (7 sets of 10 repetitions at 110% of 10-repetition maximum with 3 min rest interval). Participants were divided into two groups: high or low MQI according to 50th percentile cut-off. The responsiveness was based on minimal clinical important difference. There were no differences between groups and time on IL-6 and CK levels (p > 0.05). However, the high MQI group displayed a lower proportion of low responders (1 for laboratory and 2 for field-based vs. 5 and 4) and a higher proportion of high responders for IL-6 (7 for laboratory and 6 for field-based vs. 4 and 5) compared to low MQI group. In addition, the high MQI group showed a higher proportion of high responders for CK (11 for laboratory and 9 for field-based vs. 6 and 6) compared to low MQI. A prior MQI screening can provide feedback to understand the magnitude response. Individual responsiveness should be taken into consideration for maximizing eccentric exercise prescription.

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BACKGROUND: To investigate the time-course effects of a self-regulated training session (performed at an rating perceived exertion of 6/10), all-out session, and a control session on the metabolic, hormonal, and brain derived neurotrophic factor (BDNF) responses in Functional-Fitness (FFT) participants. METHODS: In a randomized, crossover fashion, eight healthy males (age 28.1 ± 5.4 years old; body mass 77.2 ± 4.4 kg; VO2max: 52.6 ± 4.6 mL.(kg.min)-1; 2000 m rowing test 7.35 ± 0.18 min; 1RM back squat 135.6 ± 21.9 kg) performed a FFT session under two different conditions: all-out, or with the intensity controlled to elicit an rating perceived exertion (RPE) of 6 in the Borg 10-point scale (RPE6). A control session (no exercise) was also completed. Metabolic (lactate and creatine kinase), hormonal (testosterone and cortisol), and BDNF responses were assessed pre, post-0 h, 1 h, 2 h and 24 h after the sessions. RESULTS: Creatine kinase concentrations were significantly higher (p ≤ 0.05) after 24 h for both training sessions. Total and free testosterone concentrations were lower post-2 h for all-out when compared to the RPE6 session (p ≤ 0.05). Serum cortisol concentration increased post-0 h (p = 0.011) for RPE6 and post-0 h (p = 0.003) and post-1 h (p = 0.030) for all-out session when comparing to baseline concentrations. BDNF was significantly higher (p = 0.002) post-0 h only for the all-out session when compared to baseline. A positive correlation between blood lactate concentrations and BDNF (r = 0.51; p = 0.01) was found for both effort interventions. CONCLUSIONS: A single FFT session when performed in all-out format acutely increases the concentrations of serum BDNF. However, physiological stress markers show that the all-out session requires a longer recovery period when compared to the RPE6 protocol. These findings can be helpful to coaches and practitioners design FFT session.