Transdermal oestradiol and exercise in androgen deprivation therapy (ESTRACISE): protocol.

OBJECTIVE: To report the protocol of a study evaluating the efficacy of transdermal oestradiol (E2) gel in reducing the adverse effects of androgen deprivation therapy (ADT), specifically on sexual function, and to assess the utility of E2 in combination with supervised exercise. STUDY DESIGN AND METHODS: The primary endpoint of this open-label Phase IIA randomized controlled trial is the efficacy of transdermal E2 gel. Secondary endpoints include: (i) the occurrence of ADT-induced adverse effects; (ii) the safety and tolerability of E2; (iii) the impact of E2 with or without exercise on physical, physiological, muscle, and systemic biomarkers; and (iv) quality of life. The trial will recruit high-risk PCa patients (n = 310) undergoing external beam radiation therapy with adjuvant subcutaneous ADT. Participants will be stratified and randomized in a 1:1 ratio to either the E2 + ADT arm or the ADT-only control arm. Additionally, a subset of patients (n = 120) will be randomized into a supervised exercise programme. RESULTS: The primary outcome is assessed according to the efficacy of E2 in mitigating the deterioration of Expanded Prostate Cancer Index Composite sexual function domain scores. Secondary outcomes are assessed according to the occurrence of ADT-induced adverse effects, safety and tolerability of E2, impact of E2 with or without exercise on physical performance, body composition, bone mineral density, muscle size, systematic biomarkers, and quality of life. CONCLUSION: The ESTRACISE study's innovative design can offer novel insights about the benefits of E2 gel, and the substudy can reinforce the benefits resistance training and deliver valuable new novel insights into the synergistic benefits of E2 gel and exercise, which are currently unknown. TRIAL REGISTRATION: The protocol has been registered in euclinicaltrials.eu (2023-504704-28-00) and in clinicaltrials.gov (NCT06271551).

Cortical and spinal responses to short-term strength training and detraining in young and older adults in rectus femoris muscle.

INTRODUCTION: Strength training mitigates the age-related decline in strength and muscle activation but limited evidence exists on specific motor pathway adaptations. METHODS: Eleven young (22-34 years) and ten older (66-80 years) adults underwent five testing sessions where lumbar-evoked potentials (LEPs) and motor-evoked potentials (MEPs) were measured during 20 and 60% of maximum voluntary contraction (MVC). Ten stimulations, randomly delivered, targeted 25% of maximum compound action potential for LEPs and 120, 140, and 160% of active motor threshold (aMT) for MEPs. The 7-week whole-body resistance training intervention included five exercises, e.g., knee extension (5 sets) and leg press (3 sets), performed twice weekly and was followed by 4 weeks of detraining. RESULTS: Young had higher MVC (~ 63 N·m, p = 0.006), 1-RM (~ 50 kg, p = 0.002), and lower aMT (~ 9%, p = 0.030) than older adults at baseline. Young increased 1-RM (+ 18 kg, p < 0.001), skeletal muscle mass (SMM) (+ 0.9 kg, p = 0.009), and LEP amplitude (+ 0.174, p < 0.001) during 20% MVC. Older adults increased MVC (+ 13 N·m, p = 0.014), however, they experienced decreased LEP amplitude (- 0.241, p < 0.001) during 20% MVC and MEP amplitude reductions at 120% (- 0.157, p = 0.034), 140% (- 0.196, p = 0.026), and 160% (- 0.210, p = 0.006) aMT during 60% MVC trials. After detraining, young and older adults decreased 1-RM, while young adults decreased SMM. CONCLUSION: Higher aMT and MEP amplitude in older adults were concomitant with lower baseline strength. Training increased strength in both groups, but divergent modifications in cortico-spinal activity occurred. Results suggest that the primary locus of adaptation occurs at the spinal level.

Effects of Acute Loading Induced Fatigability, Acute Serum Hormone Responses and Training Volume to Individual Hypertrophy and Maximal Strength during 10 Weeks of Strength Training.

This study investigated whether a strength training session-induced acute fatigue is related to individuals' strength training adaptations in maximal force and/or muscle hypertrophy, and whether acute responses in serum testosterone (T) and growth hormone (GH) concentrations during the training sessions would be associated with individual neuromuscular adaptations. 26 males completed the 10-week strength-training intervention, which included fatiguing dynamic leg press acute loading bouts (5 x 10 RM) at weeks two, four, six, and ten. Blood samples were collected before and after the loading and after 24h of recovery for serum T, GH, and cortisol (C) concentrations at weeks 2, 6, and 10. The cross-sectional area of the vastus lateralis was measured by ultrasonography. Isometric force measurements were performed before and immediately after loadings, and loading-induced acute decrease in maximal force was reported as the fatigue percentage. The subjects were split into three groups according to the degree of training-induced muscle hypertrophy after the training period. Increases in isometric force were significant for High Responders (HR, n = 10) (by 24.3 % ± 17.2, p = 0.035) and Medium Responders (MR, n = 7) (by 23.8 % ± 5.5, p = 0.002), whereas the increase of 26.2 % (±16.5) in Low Responders (LR, n = 7) was not significant. The amount of work (cm + s) increased significantly at every measurement point in all the groups. A significant correlation was observed between the fatigue percentage and relative changes in isometric force after the training period for the whole group (R = 0.475, p = 0.022) and separately only in HR (R = 0.643, p = 0.049). Only the HR group showed increased acute serum GH concentrations at every measurement point. There was also a significant acute increase in serum T for HR at weeks 6 and 10. HR showed the strongest correlation between acute loading-induced fatigue and isometric force gains. HR was also more sensitive to acute increases in serum concentrations of T and GH after the loading. Acute fatigue and serum GH concentrations may be indicators of responsiveness to muscle strength gain and, to some extent, muscle hypertrophy.

Effects of regular sauna bathing in conjunction with exercise on cardiovascular function: a multi-arm, randomized controlled trial.

Regular exercise and sauna bathing have each been shown to improve cardiovascular function in clinical populations. However, experimental data on the cardiovascular adaptations to regular exercise in conjunction with sauna bathing in the general population are lacking. Therefore, we compared the effects of exercise and sauna bathing to regular exercise using a multi-arm randomized controlled trial. Participants (n = 47) aged 49 ± 9 with low physical activity levels and at least one traditional cardiovascular disease (CVD) risk factor were randomly assigned (1:1:1) to guideline-based regular exercise and 15-min postexercise sauna (EXS), guideline-based regular exercise (EXE), or control (CON) for 8 wk. The primary outcomes were blood pressure (BP) and cardiorespiratory fitness (CRF). Secondary outcomes included fat mass, total cholesterol levels, and arterial stiffness. EXE had a greater change in CRF (+6.2 mL/kg/min; 95% CI, +4.2 to +8.3 mL/kg/min) and fat mass but no differences in BP when compared with CON. EXS displayed greater change in CRF (+2.7 mL/kg/min; 95% CI, +0.2 to +5.3 mL/kg/min), lower systolic BP (-8.0 mmHg; 95% CI, -14.6 to -1.4 mmHg), and lower total cholesterol levels compared with EXE. Regular exercise improved CRF and body composition in sedentary adults with CVD risk factors. However, when combined with exercise, sauna bathing demonstrated a substantially supplementary effect on CRF, systolic BP, and total cholesterol levels. Sauna bathing is a valuable lifestyle tool that complements exercise for improving CRF and decreasing systolic BP. Future research should focus on the duration and frequency of exposure to ascertain the dose-response relationship.

High Responders to Hypertrophic Strength Training Also Tend to Lose More Muscle Mass and Strength During Detraining Than Low Responders.

ABSTRACT: Räntilä, A, Ahtiainen, JP, Avela, J, Restuccia, J, Kidgell, DJ, and Häkkinen, K. High responders to hypertrophic strength training also tend to lose more muscle mass and strength during detraining than low responders. J Strength Cond Res 35(6): 1500-1511, 2021-This study investigated differences in individual responses to muscle hypertrophy during strength training and detraining. Ten weeks of resistance training was followed by 6 weeks of detraining in men (n = 24). Bilateral leg press (LP) one-repetition maximum (1RM) and maximal electromyography (EMGs) of vastus lateralis (VL) and vastus medialis, maximal voluntary activation (VA), transcranial magnetic stimulation for corticospinal excitability (CE), cross-sectional area of VL (VLCSA), selected serum hormone concentrations were measured before and repeatedly during training and detraining. In the total group, VLCSA increased by 10.7% (p = 0.025) and LP 1RM by 16.3% (p < 0.0001) after training. The subjects were split into 3 groups according to increases in VLCSA: high responders (HR) > 15% (n = 10), medium responders (MR) 15-4.5% (n = 7), and low responders (LR) < 4.5% (n = 7). Vastus lateralis CSA in HR and MR increased statistically significantly from pre to posttraining but not in LR. Only HR increased LP 1RM statistically significantly from pre to post. Maximal EMG activity increased 21.3 ± 22.9% from pre- to posttraining for the total group (p = 0.009) and for MR (p < 0.001). No significant changes occurred in VA and CE or serum hormone concentrations. During detraining, HR showed a decrease of -10.5% in VLCSA, whereas MR and LR did not. None of the subgroups decreased maximal strength during the first 3 weeks of detraining, whereas HR showed a slight (by 2.5%) rebound in strength. The present results suggest that strength gains and muscle activation adaptations may take place faster in HR and decrease also faster compared with other subgroups during detraining.

Inter-individual variation in response to resistance training in cardiometabolic health indicators.

Resistance training (RT) may improve metabolic health; however, the extent of its effectiveness is constantly evaluated to assess improvements in the group means, thus obscuring the heterogeneous individual effects. This study investigated inter-individual variation in response to RT as reflected in metabolic health indicators and how age, sex, nutrition, and pre-training phenotypes are associated with such variabilities. METHODS: Previously collected data of men and women (39-73 years, 135 trained, 73 non-trained controls) were pooled for analysis. Measurements were taken twice before training to estimate individual day-to-day variations and measurement errors (n = 208). The individual responsiveness to the 21-week RT in cardiometabolic health indicators (ie, systolic blood pressure, high-density lipoprotein cholesterol (HDL-C), cholesterol and triglycerides) was determined. Body composition was estimated by bioimpedance and dietary intake according to 4-day food diaries. RESULTS: Metabolic responses to RT seemed to be highly individual, and both beneficial and unfavorable changes were observed. Large inter-individual variations in training response were not explained by a subject's age, sex, body composition, or nutritional status, with the exception of improvements in HDL-C, which were associated with simultaneous decreases in body fat in older women. The incidence of metabolic syndrome diminished following RT. CONCLUSION: This study showed that RT could improve some specific metabolic health indicators beyond normal day-to-day variations, especially in blood lipid profile. Further studies are needed to elucidate genetic and other mechanisms underlining the heterogeneity of RT responses. This knowledge may be useful in providing individually tailored exercise prescriptions as part of personalized preventative health care.

Effects of barbell back squat stance width on sagittal and frontal hip and knee kinetics.

Different stance widths are commonly utilized when completing the barbell back squat during athletic general preparedness training. Width manipulation is thought to influence sagittal plane stimuli to the hip and knee extensors, the primary extensor musculature in the squat. However, how width manipulation affects frontal plane stimuli is less understood. Knowledge of hip and knee net joint moments (NJM) could improve exercise selection when aiming to improve sport-specific performance and prevent injuries. Fourteen adult amateur rugby athletes were recruited for this study. After a familiarization period, participants performed wide- (WIDE, 1.5× greater trochanter width) and narrow-stance (NARROW, 1× greater trochanter width) barbell back squats to femur parallel depth, using relative loads of 70% and 85% of one-repetition maximum. Sagittal and frontal plane hip and knee kinetics and kinematics were compared between widths. A Bonferroni-corrected alpha of 0.01 was employed as the threshold for statistical significance. Knee flexion angle was statistically greater in NARROW than WIDE (P < 0.0001, d = 2.56-2.86); no statistical differences were observed for hip flexion angle between conditions (P = 0.049-0.109, d = 0.33-0.38). Hip-to-knee extension NJM ratios and knee adduction NJMs were statistically greater in WIDE than NARROW (P < 0.007, d = 0.51-1.41). At femur parallel, stance width manipulation in the barbell back squat may provide substantial differences in biomechanical stimulus in both the sagittal plane and the frontal plane. In certain contexts, these differences may have clinically relevant longitudinal implications, from both a performance and a injury prevention standpoint, which are discussed.

Priming the Motor Cortex With Anodal Transcranial Direct Current Stimulation Affects the Acute Inhibitory Corticospinal Responses to Strength Training.

Frazer, AK, Howatson, G, Ahtiainen, JP, Avela, J, Rantalainen, T, and Kidgell, DJ. Priming the motor cortex with anodal transcranial direct current stimulation affects the acute inhibitory corticospinal responses to strength training. J Strength Cond Res 33(2): 307-317, 2019-Synaptic plasticity in the motor cortex (M1) is associated with strength training (ST) and can be modified by transcranial direct current stimulation (tDCS). The M1 responses to ST increase when anodal tDCS is applied during training due to gating. An additional approach to improve the M1 responses to ST, which has not been explored, is to use anodal tDCS to prime the M1 before a bout of ST. We examined the priming effects of anodal tDCS of M1 on the acute corticospinal responses to ST. In a randomized double-blinded cross-over design, changes in isometric strength, corticospinal excitability, and inhibition (assessed as area under the recruitment curve [AURC] using transcranial magnetic stimulation) were analyzed in 13 adults exposed to 20 minutes of anodal tDCS and sham tDCS followed by a ST session of the right elbow flexors. We observed a significant decrease in isometric elbow-flexor strength immediately after training (11-12%; p < 0.05), which was not different between anodal tDCS and sham tDCS. Transcranial magnetic stimulation revealed a 24% increase in AURC for corticospinal excitability after anodal tDCS and ST; this increase was not different between conditions. However, there was a 14% reduction in AURC for corticospinal inhibition when anodal tDCS was applied before ST when compared with sham tDCS and ST (all p < 0.05). Priming anodal tDCS had a limited effect in facilitating corticospinal excitability after an acute bout of ST. Interestingly, the interaction of anodal tDCS and ST seems to affect the excitability of intracortical inhibitory circuits of the M1 through nonhomeostatic mechanisms.

Determining the Corticospinal Responses to Single Bouts of Skill and Strength Training.

Mason, J, Frazer, AK, Jaberzadeh, S, Ahtiainen, JP, Avela, J, Rantalainen, T, Leung, M, and Kidgell, DJ. Determining the corticospinal responses to single bouts of skill and strength training. J Strength Cond Res 33(9): 2299-2307, 2019-Neuroplastic changes in the primary motor cortex accompany performance improvements following motor practice. Recent evidence suggests that the corticospinal responses to strength and skill training are similar, following both a single session and repeated bouts of training, promoting discussion that strength training is a form of motor learning. However, these findings are limited by the lack of a light-load strength training group. Therefore, the aim of the current study was to determine whether a single session of heavy-load strength training, light-load strength training or skill training differentially modulates the corticospinal pathway. Transcranial magnetic stimulation was used to assess the excitatory and inhibitory circuitry of the motor cortex following a single session of skill training, and following a single session of light-load and heavy-load strength training. Following a single session of training, participants in all groups experienced comparable increases in corticospinal excitability (ranging from 38 to 46%, all p < 0.05); however, disparity was observed in the inhibitory responses. Corticospinal inhibition was reduced in all 3 single-sessions, although to a greater magnitude in the heavy-load and skill-training sessions (22 and 18% respectively, compared with 11% following light-load training, all p < 0.05). Short-interval intracortical inhibition was reduced immediately following single sessions of heavy-load strength training (40% p < 0.05) and skill training (47% p < 0.05), but remained unchanged the following light-load strength training session. It appears that the corticospinal responses to single sessions of different types of strength and skill training are task-dependent. These findings reinforce the notion that strength training, at least when heavily-loaded, can be considered a form of motor learning, potentially because of the sensory feedback involved.

Physiological adaptations to resistance training in rats selectively bred for low and high response to aerobic exercise training.

NEW FINDINGS: What is the central question of this study? Can phenotypic traits associated with low response to one mode of training be extrapolated to other exercise-inducible phenotypes? The present study investigated whether rats that are low responders to endurance training are also low responders to resistance training. What is the main finding and its importance? After resistance training, rats that are high responders to aerobic exercise training improved more in maximal strength compared with low-responder rats. However, the greater gain in strength in high-responder rats was not accompanied by muscle hypertrophy, suggesting that the responses observed could be mainly neural in origin. ABSTRACT: The purpose of this study was to determine whether rats selectively bred for low and high response to aerobic exercise training co-segregate for differences in muscle adaptations to ladder-climbing resistance training. Five high-responder (HRT) and five low-responder (LRT) rats completed the resistance training, while six HRT and six LRT rats served as sedentary control animals. Before and after the 6 week intervention, body composition was determined by dual energy X-ray absorptiometry. Before tissue harvesting, the right triceps surae muscles were loaded by electrical stimulation. Muscle fibre cross-sectional areas, nuclei per cell, phosphorylation status of selected signalling proteins of mTOR and Smad pathways, and muscle protein, DNA and RNA concentrations were determined for the right gastrocnemius muscle. The daily protein synthesis rate was determined by the deuterium oxide method from the left quadriceps femoris muscle. Tissue weights of fore- and hindlimb muscles were measured. In response to resistance training, maximal carrying capacity was greater in HRT (∼3.3 times body mass) than LRT (∼2.5 times body mass), indicating greater improvements of strength in HRT. However, muscle hypertrophy that could be related to greater strength gains in HRT was not observed. Furthermore, noteworthy changes within the experimental groups or differences between groups were not observed in the present measures. The lack of hypertrophic muscular adaptations despite considerable increases in muscular strength suggest that adaptations to the present ladder-climbing training in HRT and LRT rats were largely induced by neural adaptations.

Human skeletal muscle type 1 fibre distribution and response of stress-sensing proteins along the titin molecule after submaximal exhaustive exercise.

Early responses of stress-sensing proteins, muscle LIM protein (MLP), ankyrin repeat proteins (Ankrd1/CARP and Ankrd2/Arpp) and muscle-specific RING finger proteins (MuRF1 and MuRF2), along the titin molecule were investigated in the present experiment after submaximal exhaustive exercise. Ten healthy men performed continuous drop jumping unilaterally on a sledge apparatus with a submaximal height until complete exhaustion. Five stress-sensing proteins were analysed by mRNA measurements from biopsies obtained immediately and 3 h after the exercise from exercised vastus lateralis muscle while control biopsies were obtained from non-exercised legs before the exercise. Decreased maximal jump height and increased serum creatine kinase activities as indirect markers for muscle damage and HSP27 immunostainings on muscle biopsies as a direct marker for muscle damage indicated that the current exercised protocol caused muscle damage. mRNA levels for four (MLP, Ankrd1/CARP, MuRF1 and MuRF2) out of the five studied stress sensors significantly (p < 0.05) increased 3 h after fatiguing exercise. The magnitude of MLP and Ankrd2 responses was related to the proportion of type 1 myofibres. Our data showed that the submaximal exhaustive exercise with subject's own physical fitness level activates titin-based stretch-sensing proteins. These results suggest that both degenerative and regenerative pathways are activated in very early phase after the exercise or probably already during the exercise. Activation of these proteins represents an initial step forward adaptive remodelling of the exercised muscle and may also be involved in the initiation of myofibre repair.

Physical exercise increases adult hippocampal neurogenesis in male rats provided it is aerobic and sustained.

KEY POINTS: Aerobic exercise, such as running, enhances adult hippocampal neurogenesis (AHN) in rodents. Little is known about the effects of high-intensity interval training (HIT) or of purely anaerobic resistance training on AHN. Here, compared with a sedentary lifestyle, we report a very modest effect of HIT and no effect of resistance training on AHN in adult male rats. We found the most AHN in rats that were selectively bred for an innately high response to aerobic exercise that also run voluntarily and increase maximal running capacity. Our results confirm that sustained aerobic exercise is key in improving AHN. ABSTRACT: Aerobic exercise, such as running, has positive effects on brain structure and function, such as adult hippocampal neurogenesis (AHN) and learning. Whether high-intensity interval training (HIT), referring to alternating short bouts of very intense anaerobic exercise with recovery periods, or anaerobic resistance training (RT) has similar effects on AHN is unclear. In addition, individual genetic variation in the overall response to physical exercise is likely to play a part in the effects of exercise on AHN but is less well studied. Recently, we developed polygenic rat models that gain differentially for running capacity in response to aerobic treadmill training. Here, we subjected these low-response trainer (LRT) and high-response trainer (HRT) adult male rats to various forms of physical exercise for 6-8 weeks and examined the effects on AHN. Compared with sedentary animals, the highest number of doublecortin-positive hippocampal cells was observed in HRT rats that ran voluntarily on a running wheel, whereas HIT on the treadmill had a smaller, statistically non-significant effect on AHN. Adult hippocampal neurogenesis was elevated in both LRT and HRT rats that underwent endurance training on a treadmill compared with those that performed RT by climbing a vertical ladder with weights, despite their significant gain in strength. Furthermore, RT had no effect on proliferation (Ki67), maturation (doublecortin) or survival (bromodeoxyuridine) of new adult-born hippocampal neurons in adult male Sprague-Dawley rats. Our results suggest that physical exercise promotes AHN most effectively if the exercise is aerobic and sustained, especially when accompanied by a heightened genetic predisposition for response to physical exercise.

Exercise type and volume alter signaling pathways regulating skeletal muscle glucose uptake and protein synthesis.

PURPOSE: The aim of this study was to compare activation of cellular signaling pathways regulating protein synthesis and glucose uptake in skeletal muscle between resistance and endurance exercise. Moreover, the effect of resistance exercise volume was examined. METHODS: Three groups of male volunteers (26 ± 3 years) were examined: 5 × 10 repetition maximum (RM) resistance exercise (RE) with leg press device (5 × 10 RE; n = 8), 10 × 10 RE (n = 11), and endurance exercise (strenuous 50-min walking with extra load on a treadmill; EE; n = 8). Muscle biopsies were obtained from m.vastus lateralis 30 min pre- and post-exercise. RESULTS: Downstream markers of mTORC1, p-p70S6K(Thr421/Ser424) and p-rpS6(Ser240/244), increased more after 10 × 10 RE than after 5 × 10 RE (p < 0.05) and EE (p < 0.01-0.001). Exercise-induced changes in p-IRS-I(Ser636/639) that inhibit IRS-I signaling via negative feedback from hyperactivated mTORC1 signaling were greater (p < 0.05) after 10 × 10 RE compared with 5 × 10 RE and EE. The changes in energy sensor p-AMPKα(Thr172) were greater after 10 × 10 RE and EE (p < 0.05-0.01) than after 5 × 10 RE. A major regulator of glucose uptake in muscle, p-AS160(Thr642), increased more after 10 × 10 RE than after 5 × 10 RE (p < 0.01) and EE (p < 0.05). CONCLUSION: 10 × 10 RE induced greater activation of important signaling proteins regulating glucose uptake (p-AS160) and protein synthesis (p-p70S6K, p-rpS6) than 5 × 10 RE and EE. The present findings further suggest that, especially after 10 × 10 RE, IRS-I signaling is downregulated and that AS160 is activated through AMPK signaling pathway.

Changes in corticospinal excitability during an acute bout of resistance exercise in the elbow flexors.

PURPOSE: Hypertrophic resistance exercise (HRE) induces central and peripheral fatigue. However, more detailed information about changes in corticospinal excitability remains to be elucidated. METHODS: Eleven volunteers participated in the upper arm HRE which included one repetition maximum (1 RM) control contractions and three sets of 13 RM (SET1-3). Transcranial magnetic stimulation (TMS) was applied during maximal isometric voluntary contraction (MVC) at the end of each set and during control contractions to study changes in corticospinal excitability. Electrical stimulation was used in order to measure peripheral changes. RESULTS: MVC decreased after each set when compared to control contractions. Motor evoked potential (MEP) were 138.7 ± 52.7 % (p < 0.05), 130.4 ± 44.7 and 113.1 ± 31.4 % after SET1, SET2 and SET3, respectively, when compared to pre-exercise value. A significant reduction in MEP area between SET1 and SET3 (p < 0.05) was observed while silent period (SP) duration increased (~151-165 ms, p < 0.05) simultaneously between these sets. TMS-evoked twitch force during MVC increased significantly following each set when compared to pre-exercise value. Simultaneously, a significant reduction was observed in resting twitch force over the sets. CONCLUSIONS: The results of this study clearly support the existence of both central and peripheral fatigue during HRE of elbow flexors. However, changes in the MEP area and SP suggest that during HRE of the elbow flexors, the corticospinal excitability increases first, until at some point, supraspinal fatigue takes over.

Differential modulation of corticomotor excitability in older compared to young adults following a single bout of strength -exercise.

Evidence shows corticomotor plasticity diminishes with age. Nevertheless, whether strength-training, a proven intervention that induces corticomotor plasticity in younger adults, also takes effect in older adults, remains untested. This study examined the effect of a single-session of strength-exercise on corticomotor plasticity in older and younger adults. Thirteen older adults (72.3 ± 6.5 years) and eleven younger adults (29.9 ± 6.9 years), novice to strength-exercise, participated. Strength-exercise involved four sets of 6-8 repetitions of a dumbbell biceps curl at 70-75% of their one-repetition maximum (1-RM). Muscle strength, cortical, corticomotor and spinal excitability, before and up to 60-minutes after the strength-exercise session were assessed. We observed significant changes over time (p < 0.05) and an interaction between time and age group (p < 0.05) indicating a decrease in corticomotor excitability (18% p < 0.05) for older adults at 30- and 60-minutes post strength-exercise and an increase (26% and 40%, all p < 0.05) in younger adults at the same time points. Voluntary activation (VA) declined in older adults immediately post and 60-minutes post strength-exercise (36% and 25%, all p < 0.05). Exercise had no effect on the cortical silent period (cSP) in older adults however, in young adults cSP durations were shorter at both 30- and 60- minute time points (17% 30-minute post and 9% 60-minute post, p < 0.05). There were no differences in short-interval cortical inhibition (SICI) or intracortical facilitation (ICF) between groups. Although the corticomotor responses to strength-exercise were different within groups, overall, the neural responses seem to be independent of age.

Are skeletal muscle FNDC5 gene expression and irisin release regulated by exercise and related to health?

Recently, contradictory findings have been reported concerning the function of irisin and its precursor gene, skeletal muscle FNDC5, in energy homeostasis, and the associated regulatory role of exercise and PGC-1α. We therefore evaluated whether muscle FNDC5 mRNA and serum irisin are exercise responsive and whether PGC-1α expression is associated with FNDC5 expression. The male subjects in the study performed single exercises: (1) 1 h low-intensity aerobic exercise (AE) (middle-aged, n = 17), (2) a heavy-intensity resistance exercise (RE) bout (young n = 10, older n = 11) (27 vs. 62 years), (3) long-term 21 weeks endurance exercise (EE) training alone (twice a week, middle-aged, n = 9), or (4) combined EE and RE training (both twice a week, middle-aged, n = 9). Skeletal muscle mRNA expression was analysed by quantitative PCR and serum irisin by ELISA. No significant changes were observed in skeletal muscle PGC-1α, FNDC5 and serum irisin after AE, EE training or combined EE + RE training. However, a single RE bout increased PGC-1α by 4-fold in young and by 2-fold in older men, while FNDC5 mRNA only increased in young men post-RE, by 1.4-fold. Changes in PGC-1α or serum irisin were not consistently accompanied by changes in FNDC5. In conclusion, for the most part, neither longer-term nor single exercise markedly increases skeletal muscle FNDC5 expression or serum irisin. Therefore their changes in response to exercise are probably random and not consistent excluding the confirmation of any definitive link between exercise and FNDC5 expression and irisin release in humans. Moreover, irisin and FNDC5 were not associated with glucose tolerance and being overweight, or with metabolic disturbances, respectively. Finally, factor(s) other than PGC-1α and transcription may regulate FNDC5 expression.

Variable resistance training promotes greater fatigue resistance but not hypertrophy versus constant resistance training.

Loading using variable resistance devices, where the external resistance changes in line with the force:angle relationship, has been shown to cause greater acute neuromuscular fatigue and larger serum hormone responses. This may indicate a greater potential for adaptation during long-term training. Twelve (constant resistance group) and 11 (variable resistance group) men completed 20 weeks of resistance training with 10 men as non-training controls. Training-induced adaptations were assessed by bilateral leg press one repetition maximum, a repetition to failure test using 75 % 1RM, lower limb lean mass and vastus lateralis cross-sectional area. Only the variable resistance training group improved the total number of repetitions (41 ± 46 %) and volume load (52 ± 37 %) during the repetition to failure test (P < 0.05). Similar improvements in maximum strength and hypertrophy of the lower limbs were observed in both training groups. Also, constant and variable resistance 5 × 10RM leg press loadings were performed before and after training in a crossover design. Acute loading-induced responses were assessed by concentric and isometric force, serum hormone concentrations and phosphorylation of intramuscular signalling proteins (0-30 min post-loading). Greater acute decreases in force (P < 0.05-0.01), and greater increases in serum testosterone and cortisol concentration (P < 0.05) and ERK 1/2 phosphorylation (P < 0.05) were observed following variable resistance loadings before and after training. Greater training-induced improvements in fatigue resistance occurred in the variable resistance training group, which may be due to greater acute fatigue and physiological responses during variable versus constant resistance loadings.

Periodised Carbohydrate Intake Does Not Affect Substrate Oxidation but May Contribute to Endurance Capacity.

The aim of this study was to investigate whether periodising carbohydrate intake around specific training sessions will enhance endurance training adaptations.Seventeen healthy recreationally endurance-trained males (n = 5) and females (n = 12) (27.5 ± 5.4 years) participated in a four-week training intervention. Participants were divided into two groups: FASTED (stayed fasted between evening high-intensity interval training session and low-intensity training session in the following morning) and FED (no restriction in food intake). Pre- and post-testing included peak oxygen uptake (VO2peak), anaerobic capacity, and 60 min submaximal running tests. Fasted venous blood samples were drawn for the determination of triglyceride and glucose concentrations.VO2peak increased in both FASTED (4.4 ± 3.0%, p = 0.001) and FED (4.6 ± 4.2%, p = 0.017), whereas maximal running velocity increased only in the FASTED (3.5 ± 2.7%, p = 0.002). Lactate concentrations in the anaerobic test after intervention were greater in FASTED than FED (p = 0.025-0.041). Running time in the anaerobic test was improved in FASTED (from 64.1 ± 15.6-86.3 ± 23.2 s, p < 0.001) but not in FED (from 56.4 ± 15.2-66.9 ± 21.3 s, p = 0.099). Substrate oxidation did not change after intervention in either of the groups (p = 0.052-0.597). Heart rate was lower in the submaximal running test in FASTED (p < 0.001) but not in FED (p = 0.097).Training with periodised carbohydrate availability does not have any effect on substrate oxidation. However, it seems to enhance the capacity to perform high-intensity exercise.

Weight loss induces changes in adaptive thermogenesis in female and male physique athletes.

Physique athletes lose substantial weight preparing for competitions, potentially altering systemic metabolism. We investigated sex differences in body composition, resting energy expenditure (REE), and appetite-regulating and thyroid hormone changes during a competition preparation among drug-free physique athletes. The participants were female (10 competing (COMP) and 10 nondieting controls (CTRL)) and male (13 COMP and 10 CTRL) physique athletes. COMP were tested before they started their diet 23 weeks before competing (PRE), during their diet one week before competing (MID), and 23 weeks after competing (POST), whereas CTRL were tested at similar intervals but did not diet. Measurements included body composition by dual-energy X-ray absorptiometry, muscle size, and subcutaneous fat thickness (SFA) by ultrasound, REE by indirect calorimetry, circulating ghrelin, leptin T3, and T4 hormone analysis. Fat mass (FM) and SFA decreased in both sexes (p < 0.001), while males (p < 0.001) lost more lean mass (LM) than females (p < 0.05). Weight loss, decreased energy intake, and increased aerobic exercise (p < 0.05) led to decreased LM- and FM-adjusted REE (p < 0.05), reflecting metabolic adaptation. Absolute leptin levels decreased in both sexes (p < 0.001) but more among females (p < 0.001) due to higher baseline leptin levels. These changes occurred with similar decreases in T3 (p < 0.001) and resting heart rate (p < 0.01) in both sexes. CTRL, who were former or upcoming physique athletes, showed no systematic changes in any measured variables. In conclusion, while dieting, female and male physique athletes experience REE and hormonal changes leading to adaptive thermogenesis. However, responses seemed temporary as they returned toward baseline after the recovery phase. ClinicalTrials.gov (NCT04392752).