Zfp697 is an RNA-binding protein that regulates skeletal muscle inflammation and remodeling.

Skeletal muscle atrophy is a morbidity and mortality risk factor that happens with disuse, chronic disease, and aging. The tissue remodeling that happens during recovery from atrophy or injury involves changes in different cell types such as muscle fibers, and satellite and immune cells. Here, we show that the previously uncharacterized gene and protein Zfp697 is a damage-induced regulator of muscle remodeling. Zfp697/ZNF697 expression is transiently elevated during recovery from muscle atrophy or injury in mice and humans. Sustained Zfp697 expression in mouse muscle leads to a gene expression signature of chemokine secretion, immune cell recruitment, and extracellular matrix remodeling. Notably, although Zfp697 is expressed in several cell types in skeletal muscle, myofiber-specific Zfp697 genetic ablation in mice is sufficient to hinder the inflammatory and regenerative response to muscle injury, compromising functional recovery. We show that Zfp697 is an essential mediator of the interferon gamma response in muscle cells and that it functions primarily as an RNA-interacting protein, with a very high number of miRNA targets. This work identifies Zfp697 as an integrator of cell-cell communication necessary for tissue remodeling and regeneration.

Mood, Cognitive Function, and Plasma Kynurenine Metabolites Responses Following Severe Changes in Physical Activity.

PURPOSE: To monitor changes in mood, cognitive function, brain electrical activity, and circulating kynurenine pathway metabolites in response to a three-week severe physical activity restriction, followed by three weeks of resumed activity adding resistance and high-intensity interval exercise training. METHODS: Twenty healthy participants (14 males, six females; 25.4 ± 5.2 years) underwent three weeks of limited physical activity using forearm crutches with one leg suspended (INACT) and then three weeks of resumed activity plus supervised resistance and high-intensity interval training sessions (ACT, three to six sessions per week). At baseline, after INACT, and then after ACT, venous blood was sampled for analysis of major kynurenine pathway metabolites, a short version of the International Physical Activity Questionnaire (IPAQ-SF), Hospital Anxiety and Depression Scale (HADS) and Profile of Mood States (POMS) questionnaires were completed, and cognitive tests with EEG were performed. RESULTS: During INACT, the depression score on the HADS scale tended to increase (3.5 to 6.8; p = 0.065), while it was reduced with ACT compared with after INACT (2.8; p = 0.022). On the POMS scale, depression, fatigue, and confusion increased within INACT (p < 0.05). Notably, subjects exhibited considerable variability, and those experiencing depression symptoms recorded by the HADS scale (n = 4) displayed distinct mood disturbances on POMS. All HADS and POMS scores were fully restored to baseline with ACT. Neither INACT nor ACT induced significant changes in cognition, brain electrical activity, or kynurenine pathway metabolites (p > 0.05). CONCLUSIONS: While young healthy individuals with three weeks of severely restricted physical activity do not undergo changes in circulating kynurenine pathway metabolites, cognitive performance, and brain electrical activity, their mood response is quite variable, and depression develops in some. Three weeks of resuming mobility plus exercise training reversed the mood profile.

Cell-free DNA kinetics in response to muscle-damaging exercise: A drop jump study.

A significant increase in circulating cell-free DNA (cfDNA) occurs with physical exercise, which depends on the type of exertion and the duration. The aims of this study were as follows: (1) to investigate the time course of cfDNA and conventional markers of muscle damage from immediately after to 96 h after muscle-damaging exercise; and (2) to investigate the relationship between cfDNA and indicators of primary (low-frequency fatigue and maximal voluntary isometric contraction) and secondary (creatine kinase and delayed-onset muscle soreness) muscle damage in young healthy males. Fourteen participants (age, 22 ± 2 years; weight, 84.4 ± 11.2 kg; height, 184.0 ± 7.4 cm) performed 50 intermittent drop jumps at 20 s intervals. We measured cfDNA and creatine kinase concentrations, maximal voluntary isometric contraction torque, low-frequency fatigue and delayed-onset muscle soreness before and at several time points up to 96 h after exercise. Plasma cfDNA levels increased from immediately postexercise until 72 h postexercise (P < 0.01). Elevation of postexercise cfDNA was correlated with both more pronounced low-frequency fatigue (r = -0.52, P = 3.4 × 10-11) and delayed-onset muscle soreness (r = 0.32, P = 0.00019). Levels of cfDNA change in response to severe primary and secondary muscle damage after exercise. Levels of cfDNA exhibit a stronger correlation with variables related to primary muscle damage than to secondary muscle damage, suggesting that cfDNA is a more sensitive marker of acute loss of muscle function than of secondary inflammation or damaged muscle fibres.

Exploring the effect of prolonged fasting on kynurenine pathway metabolites and stress markers in healthy male individuals.

BACKGROUND/OBJECTIVES: Prolonged fasting triggers a stress response within the human body. Our objective was to investigate the impact of prolonged fasting, in conjunction with stress, on kynurenine pathway metabolites. SUBJECTS/METHODS: Healthy males were divided into fasting group (zero-calorie-restriction) for 6 days (FAST, n = 14), and control group (CON, n = 10). Blood and saliva samples were collected at baseline, Day 2, Day 4, Day 6 during fasting period, and 1 week after resuming regular diet. Plasma levels of kynurenine pathway metabolites were measured using ultra-performance liquid chromatography-mass spectrometry (UPLC-MS/MS). Plasma and salivary samples were analyzed for stress markers. RESULTS: A pronounced activation of the kynurenine pathway in individuals on FAST trial was revealed. Concentrations of picolinic acid (PIC), kynurenic acid (KYNA) and 3-hydroxykynurenine (3-HK) were significantly increased, with peak levels observed on Day 6 (P < 0.0001). Conversely, concentrations of tryptophan (TRP) and quinolinic acid (QUIN) decreased (P < 0.0001), while kynurenine (KYN) and nicotinamide (NAM) levels remained stable. Cortisol and noradrenaline concentrations remained unchanged. However, adrenaline levels significantly increased on Day 4 within FAST compared to CON (P = 0.005). Notably, all deviations in kynurenine pathway metabolite levels returned to baseline values upon resuming regular diet following the 6-day fasting regimen, even when weight and BMI parameters were not restored. CONCLUSIONS: Extended fasting over 6 days induces the kynurenine pathway and has minimal effects on stress markers. Restoration of metabolite concentrations upon regular feeding implies rapid adaptation of the kynurenine pathway synthetic enzymes to maintain homeostasis when faced with perturbations.

Near-InfraRed Spectroscopy Provides a Reproducible Estimate of Muscle Aerobic Capacity, but Not Whole-Body Aerobic Power.

Near-infrared spectroscopy (NIRS) during repeated limb occlusions is a noninvasive tool for assessing muscle oxidative capacity. However, the method's reliability and validity remain under investigation. This study aimed to determine the reliability of the NIRS-derived mitochondrial power of the musculus vastus lateralis and its correlation with whole-body (cycling) aerobic power (V̇O2 peak). Eleven healthy active men (28 ± 10 y) twice (2 days apart) underwent repeated arterial occlusions to induce changes in muscle oxygen delivery after 15 s of electrical muscle stimulation. The muscle oxygen consumption (mV̇O2) recovery time and rate (k) constants were calculated from the NIRS O2Hb signal. We assessed the reliability (coefficient of variation and intraclass coefficient of correlation [ICC]) and equivalency (t-test) between visits. The results showed high reproducibility for the mV̇O2 recovery time constant (ICC = 0.859) and moderate reproducibility for the k value (ICC = 0.674), with no significant differences between visits (p > 0.05). NIRS-derived k did not correlate with the V̇O2 peak relative to body mass (r = 0.441, p = 0.17) or the absolute V̇O2 peak (r = 0.366, p = 0.26). In conclusion, NIRS provides a reproducible estimate of muscle mitochondrial power, which, however, was not correlated with whole-body aerobic capacity in the current study, suggesting that even if somewhat overlapping, not the same set of factors underpin these distinct indices of aerobic capacity at the different (peripheral and whole-body systemic) levels.

Passive heating-induced changes in muscle contractile function are not further augmented by prolonged exposure in young males experiencing moderate thermal stress.

Background: We investigated the impact of 1) passive heating (PH) induced by single and intermittent/prolonged hot-water immersion (HWI) and 2) the duration of PH, on muscle contractile function under the unfatigued state, and during the development of muscle fatigue. Methods: Twelve young males volunteered for this study consisting of two phases: single phase (SP) followed by intermittent/prolonged phase (IPP), with both phases including two conditions (i.e., four trials in total) performed randomly: control passive sitting (CON) and HWI (44-45°C; water up to the waist level). SP-HWI included one continuous 45-min bath (from 15 to 60 min). IPP-HWI included an initial 45-min bath (from 15 to 60 min) followed by eight additional 15-min baths interspaced with 15-min breaks at room temperature between 75 and 300 min. Intramuscular (Tmu; measured in the vastus lateralis muscle) and rectal (Trec) temperatures were determined. Neuromuscular testing (performed in the knee extensors and flexors) was performed at baseline and 60 min later during SP, and at baseline, 60, 90, 150 and 300 min after baseline during IPP. A fatiguing protocol (100 electrical stimulations of the knee extensors) was performed after the last neuromuscular testing of each trial. Results: HWI increased Tmu and Trec to 38°C-38.5°C (p < 0.05) during both SP and IPP. Under the unfatigued state, HWI did not affect electrically induced torques at 20 Hz (P20) and 100 Hz (P100). However, it induced a shift towards a faster contractile profile during both SP and IPP, as evidenced by a decreased P20/P100 ratio (p < 0.05) and an improved muscle relaxation (i.e., reduced half-relaxation time and increased rate of torque relaxation; p < 0.05). Despite a reduced voluntary activation (i.e., -2.63% ± 4.19% after SP-HWI and -5.73% ± 4.31% after IPP-HWI; condition effect: p < 0.001), HWI did not impair maximal isokinetic and isometric contraction torques. During the fatiguing protocol, fatigue index and the changes in muscle contractile properties were larger after HWI than CON conditions (p < 0.05). Finally, none of these parameters were significantly affected by the heating duration. Conclusion: PH induces changes in muscle contractile function which are not augmented by prolonged exposure when thermal stress is moderate.

Three-week sprint interval training (SIT) reduces cell-free DNA and low-frequency fatigue but does not induce VO2max improvement in older men.

PURPOSE: This study aimed to investigate the impact of sprint interval training (SIT) on both the acute and 3-week modulations of cell-free DNA (cfDNA), as well as its association with neuromuscular fatigue and physical performance in healthy young and old men. METHODS: Ten young (20-25 year old) and nine elderly (63-72 year old) healthy men performed nine SIT sessions consisting of 4-to-6-all-out cycling repetitions of 30 s interspaced with 4-min rest intervals. We compared the maximal voluntary contractions torque, central activation ratio, low-frequency fatigue (LFF), and cfDNA concentrations between the groups before, immediately after, 1 h after, and 24 h after the first and ninth SIT sessions. RESULTS: The plasma cfDNA levels were increased post-exercise (from 1.4 ± 0.258 to 1.91 ± 0.278 ng/ml (P < 0.01) on a log10 scale), without significant differences between the groups. However, older individuals showed a slight decrease in the baseline cfDNA values, from 1.39 ± 0.176 to 1.29 ± 0.085 ng/ml on a log10 scale, after 3 weeks (P = 0.043). Importantly, the elevation of the post-exercise cfDNA values was correlated with an increase in LFF in both groups. Three weeks of SIT induced an improvement in the recovery of LFF (main session effect, P = 0.0029); however, only the young group showed an increase in aerobic capacity (VO2max) (from 40.8 ± 6.74 to 43.0 ± 5.80 ml/kg/min, P = 0.0039). CONCLUSION: Three weeks of SIT diminished the baseline cfDNA values in the old group, together with an improvement in the recovery of LFF. However, VO2max was increased only in the young group.

Fasting for 48 h induced similar glucose intolerance in both sexes despite greater perceived stress and decreased estradiol levels in females.

PURPOSE: The purpose of this study was to compare the effects of fasting for 48 h on the evoked insulin and glucose responses in males and females, and to explore factors such as stress and estrogen levels that might influence these responses. METHODS: Healthy, nonobese male (n = 14) and female (n = 14) subjects underwent 48-h fasting trial. Changes in glucose tolerance and insulin levels in response to the oral glucose tolerance test, subjectively perceived stress and catecholamine concentrations were measured in all participants. Estrogen levels were also measured in the female participants during the 48-h fast. RESULTS: Glucose area under the curve (AUC) values increased similarly in both sexes after 48-h fasting (P < 0.05), but females displayed a greater rise in insulin AUC values than males (P < 0.05). Fasting increased plasma epinephrine concentrations in both sexes (P < 0.05), whereas plasma norepinephrine concentrations and subjective stress increased only in females (P < 0.05). Plasma 17-ß-estradiol concentrations in females decreased after fasting (P < 0.05). CONCLUSION: Fasting for 48 h induced a similar glucose intolerance in females and males, despite decreased 17-ß-estradiol levels and greater psychological and physiological stress in females. These differences represent a plausible explanation for the gender-based differences observed in insulin responses. TRIAL REGISTRATION: Retrospectively registered on ClinicalTrials.gov (NCT05545943) in September 19, 2022.

Age-Related Difference in Cognitive Performance under Severe Whole-Body Hyperthermia Parallels Cortisol and Physical Strain Responses.

Background and Objectives: To date, understanding age-related changes in cognitive processes during heat exposure still needs to be better-understood. Thus, the main aim of the current study was to evaluate the effects of whole-body hyperthermia (WBH), i.e., a ≈ 2.5 °C increase in rectal temperature (Tre) from overnight-fast baseline value, on cognitive functioning in old and young men and to explore factors, such as stress and thermophysiological strain, that could influence such changes. Materials and Methods: Ten young (19-21 years of age) and nine old (61-80 years of age) healthy men underwent an experimental trial with passive lower-body heating in hot water immersion (HWI) at 43 °C (HWI-43 °C) until Tre reached 39 °C in old adults and 39.5 °C in young adults. Cognitive performance and cortisol concentration were assessed before and after HWI, and the physiological strain index (PSI) was assessed during HWI-43 °C. Results: PSI was lower and cortisol concentration was greater after HWI-43 °C in the old group compared with the young group (p < 0.05). Surprisingly, hyperthermia improved cognitive flexibility only in old adults, whereas short-term and visual recognition memories were maintained in both age groups. Conclusions: A ≈ 2.5 °C increase in rectal temperature can improve executive function in old adults, and this increase parallels the increased cortisol concentration and the lower thermophysiological strain under severe WBH conditions.

Short-duration cold exposure decreases fasting-induced glucose intolerance but has no effect on resting energy expenditure.

The aim of the present study was to investigate whether brief cold exposure can reverse fasting-induced glucose intolerance and insulin resistance, and improve resting energy expenditure (REE). Twelve young non-obese women were randomly assigned to undergo the following conditions: 2 days of fasting with two 10-min whole-body cold-water immersions on separate days (FAST-COLD), 2 days of fasting without cold-water immersions (FAST), 2 days of usual diet with two 10-min whole-body cold-water immersions on separate days (COLD), or 2 days of usual diet without cold-water immersions (CON) in a randomised crossover fashion. Changes in REE and substrate utilisation, and glucose tolerance and insulin sensitivity from the oral glucose tolerance test were examined. The results showed that FAST-COLD and FAST trials increased (P < 0.05) REE and decreased (P < 0.05) respiratory quotient, but these variables did not differ significantly between the FAST-COLD and FAST trials. The glucose and insulin area under the curves (AUCs) were higher (P < 0.05) in the FAST-COLD and FAST trials than in the CON and COLD trials, and these AUCs were lower (P < 0.05) in the FAST-COLD than in the FAST trial. Matsuda index was lower in the FAST trial than in the CON trial (P < 0.05), and tended to be greater after the FAST-COLD trial than after the FAST trial (P = 0.060). In conclusion, cold exposure had no effect on REE but decreased fasting-induced glucose intolerance which was accompanied by a maintained insulin sensitivity.

Zfp697 is an RNA-binding protein that regulates skeletal muscle inflammation and regeneration.

Muscular atrophy is a mortality risk factor that happens with disuse, chronic disease, and aging. Recovery from atrophy requires changes in several cell types including muscle fibers, and satellite and immune cells. Here we show that Zfp697/ZNF697 is a damage-induced regulator of muscle regeneration, during which its expression is transiently elevated. Conversely, sustained Zfp697 expression in mouse muscle leads to a gene expression signature of chemokine secretion, immune cell recruitment, and extracellular matrix remodeling. Myofiber-specific Zfp697 ablation hinders the inflammatory and regenerative response to muscle injury, compromising functional recovery. We uncover Zfp697 as an essential interferon gamma mediator in muscle cells, interacting primarily with ncRNAs such as the pro-regenerative miR-206. In sum, we identify Zfp697 as an integrator of cell-cell communication necessary for tissue regeneration.

Age-related differences in the neuromuscular performance of fatigue-provoking exercise under severe whole-body hyperthermia conditions.

PURPOSE: The purpose of this study was to determine if aging would lead to greater decline in neuromuscular function during a fatiguing task under severe whole-body hyperthermia conditions. METHODS: Twelve young (aged 19-21 years) and 11 older (aged 65-80 years) males were enrolled in the study, which comprised a randomized control trial under a thermoneutral condition at an ambient temperature of 23°C (CON) and an experimental trial with passive lower body heating in 43°C water (HWI-43°C). Changes in neuromuscular function and fatigability, and physical performance-influencing factors such as psychological, thermoregulatory, neuroendocrine, and immune responses to whole-body hyperthermia were measured. RESULTS: A slower increase in rectal temperature, and a lower heart rate, thermal sensation, and sweating rate were observed in older males than young males in response to HWI-43°C trial (p < 0.05). Nevertheless, prolactin increased more in response to hyperthermia in young males, while interleukin-6 and cortisol levels increased more in older males (p < 0.05). Peripheral dopamine levels decreased in older males and increased in young males in response to hyperthermia (p < 0.05). Surprisingly, older males demonstrated greater neuromuscular fatigability resistance and faster maximal voluntary contraction (MVC) torque recovery after a 2-min sustained isometric MVC task under thermoneutral and severe hyperthermic conditions (p < 0.05). CONCLUSION: Neuromuscular performance during fatigue-provoking sustained isometric exercise under severe whole-body hyperthermia conditions appears to decline in both age groups, but a lower relative decline in torque production for older males may relate to lower psychological and thermophysiological strain along with a diminished dopamine response and prolactin release.

Moderate muscle cooling induced by single and intermittent/prolonged cold-water immersions differently affects muscle contractile function in young males.

Background: We investigated the impact of moderate muscle cooling induced by single and intermittent/prolonged cold-water immersions (CWI) on muscle force and contractility in unfatigued state and during the development of fatigue resulting from electrically induced contractions. Methods: Twelve young males participated in this study consisting of two phases [single phase (SP) followed by intermittent/prolonged phase (IPP)], with both phases including two conditions (i.e., four trials in total) performed randomly: control passive sitting (CON) and cold-water immersions (10°C). SP-CWI included one 45 min-bath (from 15 to 60 min). IPP-CWI included three baths (45 min-bath from 15 to 60 min, and 15 min-baths from 165 to 180 min and from 255 to 270 min), with participants sitting at room temperature the rest of the time until 300 min. Blood pressure and intramuscular (Tmu) temperature were assessed, and neuromuscular testing was performed at baseline and 60 min after baseline during SP, and at baseline, 60, 90, 150 and 300 min after baseline during IPP. A fatiguing protocol (100 electrical stimulations) was performed after the last neuromuscular testing of each trial. Results: In unfatigued state, SP-CWI and IPP-CWI reduced electrically induced torque at 100 Hz (P100) but not at 20 Hz (P20), and increased P20/P100 ratio. The changes from baseline for P100 and P20/P100 ratio were lower in IPP-CWI than SP-CWI. Both cold-water immersion conditions slowed down muscle contraction and relaxation, and reduced maximal isokinetic contraction torque, but the changes from baseline were lower after IPP-CWI than SP-CWI. cold-water immersions did not impair maximal voluntary isometric contraction. During the fatiguing protocol, torque fatigue index and the changes in muscle contractile properties were larger after IPP-CWI than SP-CWI, but were in the same range as after CON conditions. The differences of muscle contractile function between SP-CWI and IPP-CWI were accompanied by a lower reduction of superficial Tmu and a smaller increase in systolic blood pressure after IPP-CWI than SP-CWI. Conclusion: IPP-CWI induces a less pronounced fast-to-slow contractile transition compared to SP-CWI, and this may result from the reduced vasoconstriction response and enhanced blood perfusion of the superficial muscle vessels, which could ultimately limit the reduction of superficial Tmu.

Prolonged fasting outperforms short-term fasting in terms of glucose tolerance and insulin release: a randomised controlled trial.

Fasting is related to glucose intolerance and insulin resistance, but it is unknown whether the duration of fasting influences these factors. We explored whether prolonged fasting increases norepinephrine and ketone concentrations and decreases core temperature to a greater extent than short-term fasting; if so, this should lead to improved glucose tolerance. Forty-three healthy young adult males were randomly assigned to undergo a 2-d fast, 6-d fast or the usual diet. Changes in rectal temperature (TR), ketone and catecholamine concentrations, glucose tolerance and insulin release in response to an oral glucose tolerance test were assessed. Both fasting trials increased ketone concentration, and the effect was larger after the 6-d fast (P < 0·05). TR and epinephrine concentration increased only after the 2-d fast (P < 0·05). Both fasting trials increased the glucose area under the curve (AUC) (P < 0·05), but the AUC remained higher than the baseline value after participants returned to their usual diet in the 2-d fast group (P < 0·05). Neither fasting had an immediate effect on the insulin AUC, although it increased after return to their usual diet in the 6-d fast group (P < 0·05). These data suggest that the 2-d fast elicited residual impaired glucose tolerance, which may be linked to greater perceived stress during short-term fasting, as shown by the epinephrine response and change in core temperature. By contrast, prolonged fasting seemed to evoke an adaptive residual mechanism that is related to improved insulin release and maintained glucose tolerance.

Effects of short bout small-sided game training on acid-based balance markers in youth male soccer players.

This study aimed to compare the effects of 1 × 1 small-sided games (SSGs) with different bout durations on external (ETL) and internal training loads (ITL) in youth soccer players. Twenty U18 players were divided into two groups performing six 1 × 1 SSGs with 30 and 45 s bout durations on a playing field of 10 by 15 m. ITL indices, including the percentage of maximum heart rate (HR), blood lactate (BLa) level, pH, bicarbonate (HCO3-) level, and base excess (BE) level, were measured at rest, after each SSG bout, and 15 and 30 min after the entire exercise protocol. ETL (Global Positioning System metrics) was recorded during all six SSG bouts. The analysis showed that the 45 s SSGs had a greater volume (large effect) but a lower training intensity (small to large effect) than the 30 s SSGs. A significant time effect (p < 0.05) was observed in all ITL indices and a significant group effect (F1, 18 = 8.84, p = 0.0082, ƞ2 = 0.33) in the HCO3- level only. Finally, the changes in the HR and HCO3- level were smaller in the 45 s SSGs than in the 30 s SSGs. In conclusion, 30-s games, characterized by a higher intensity of training effort, are more physiologically demanding than 45-s games. Secondly during short-bout SSG training the HR and BLa level have limited diagnostic value for ITL. Extending ITL monitoring using other indicators, such as the HCO3- and BE levels, appears reasonable.

Regular short-duration breaks do not prevent mental fatigue and decline in cognitive efficiency in healthy young men during an office-like simulated mental working day: An EEG study.

Employees in Europe work on average 7.2 h per day. Prolonged periods of uninterrupted cognitive activity during the working day can cause changes in motivation, mental fatigue, and deterioration in cognitive function. In this exploratory study, we aimed to determine the effectiveness of taking 10-min breaks for light exercise every 50 min in preventing these negative effects during a simulated 7-h office-like computer work. Eighteen healthy young adult men (aged 26 ± 3 years) who did not work in an office participated. The effects of 7 h of office-like work with 10-min breaks every 50 min on central nervous system activity, cognitive function, mood, and motivation were investigated and compared with those measured on a control day without work. Our study found that engaging in 7 h of mental work similar to that found in an office environment, with 10-min breaks every 50 min, can negatively impact cognitive efficiency, suppress brain neural network activity, and cause mental fatigue. These effects do not fully recover after a 4.5-h rest. Additionally, taking short breaks during the workday does not prevent mental exhaustion or impairments in cognitive function. These findings should be considered when discussing strategies to prevent mental exhaustion caused by mental work.

Changes in irisin, inflammatory cytokines and aerobic capacity in response to three weeks of supervised sprint interval training in older men.

BACKGROUND: This study investigated the effects of supervised short-term sprint interval training (SIT) on circulating irisin, interleukin (IL)-6 and tumour necrosis factor (TNF)-α concentrations, and aerobic capacity and body composition values in healthy older men. METHODS: Eleven older men (63±8 years; 178.0±5.5 cm; 82.7±8.6 kg; 22.7±3.7% body fat) underwent SIT (6 repetitions of 30 s all-out cycling bouts with 4 min active recovery after each bout) three days a week for three consecutive weeks. Body composition measured by dual-energy X-ray absorptiometry, aerobic capacity assessed by direct peak oxygen consumption (VO2peak) test and morning fasting blood samples were obtained before and after a 3-week SIT intervention. RESULTS: Nine supervised SIT sessions moderately (effect size [ES] =0.65; P<0.05) increased irisin concentrations (from 135.40±28.73 to 154.20±47.09 ng.mL-1) together with moderate decreases (P<0.05) in IL-6 (ES=0.89; from 1.26±0.44 to 0.87±0.44 pg.mL-1) and TNF-α (ES=0.64; from 5.10±1.23 to 4.31±1.20 pg.mL-1) levels in older men. In addition, increase in VO2peak was significant but small (ES=0.25; P<0.05; from 36.0±7.1 to 37.8±6.7 mL.min.-1kg-1), while no changes (P>0.05) in body composition variables were observed after a short-term SIT period. CONCLUSIONS: A 3-week SIT intervention with only nine training sessions increased circulating irisin concentrations, improved inflammatory profile and aerobic capacity without changes in body composition in healthy older men. Accordingly, a short-term SIT programme is a time efficient alternative for traditional aerobic training to improve metabolic health and aerobic capacity in older adults.

Kinetics of lipid indicators in response to short- and long-duration whole-body, cold-water immersion.

Cold exposure-induced secretion of stress hormones activates cold-defense responses and mobilizes substrates for increased energy demands to fuel thermogenesis. However, it is unclear whether acute cold exposure-induced stress hormone response kinetics affect circulating lipid parameter kinetics. Therefore, we aimed to investigate the 2-day kinetics of stress hormones (i.e., cortisol, epinephrine, and norepinephrine) and the lipid profile (i.e., total cholesterol [TC], high-density lipoprotein [HDL] cholesterol, low-density lipoprotein [LDL] cholesterol, and triglycerides) in response to whole-body long- (intermittent 170 min; 170-CWI) or short-duration (10 min; 10-CWI) cold-water immersion (CWI; 14 °C water) in 17 healthy, young, adult men. Both CWI trials induced a marked release of the stress hormones, epinephrine, and norepinephrine, with higher concentrations detected after 170-CWI (p < 0.05) and a disrupted diurnal peak of cortisol lasting for a few hours. 170-CWI increased triglyceride levels from immediately after until 2 h after CWI, thereafter the concentration decreased at 4 h, 6 h, 1 day and 2 days after CWI (p < 0.05). Furthermore, the HDL-cholesterol level increased immediately after and at 6 h after 170-CWI (p < 0.05), while TC and LDL-cholesterol levels were not altered within 2 days. Lipid parameters were not affected within the 2 days after 10-CWI. Although both CWIs decreased deep body temperature and increased stress hormone levels for a few hours, only long-duration CWI induced changes in the circulating lipid profile within 2 days after CWI. This should be considered when discussing therapeutic protocols to improve circulating lipid profiles and ameliorate diseases associated with such profiles.

Modulation of neuromuscular excitability in response to acute noxious heat exposure has no additional effects on central and peripheral fatigability.

Background: Whole-body hyperthermia (WBH) has an adverse effect on the nervous system and neurophysiological performance. In the present study, we examined whether short-duration whole-body immersion in 45°C water (HWI-45°C), which produces a strong neural and temperature flux without inducing WBH, can increase or impair neurophysiological performance in humans. Methods: Fifteen men (aged 25 ± 6 years) were enrolled in this study and participated in three experiments: 1) a brief (5-min) immersion of the whole body in 37°C water (WI-37°C); 2) a brief (5-min) HWI-45°C; and 3) a control trial in a thermoneutral condition at an ambient temperature of 24°C and 60% relative humidity. Before and after the immersions, neuromuscular function (electromyographic activity, reflexes, electrically and voluntary induced torque production, voluntary muscle activation level) were tested. To provoke central inhibition, the participants performed a sustained 2-min maximal voluntary contraction (MVC). Results: Thermophysiological strain was greater after HWI-45°C than after WI-37°C. Electrophysiological modulations of motor drive transmission and peripheral modulations of muscle contractility properties in response to HWI-45°C seemed to have little effect on central activation of the exercising muscles and no effect on MVC production. Conclusion: Although exposure to acute noxious heat was effective in evoking neuromuscular excitability, the increases in core temperature (∼0.2°C) and muscle temperature (∼0.6°C) did not induce moderate or severe WBH. These changes did not seem to affect central structures; that is, there were no additional increases in central and/or peripheral fatigue during a sustained 2-min MVC.

Two-day fasting affects kynurenine pathway with additional modulation of short-term whole-body cooling: a quasi-randomised crossover trial.

Metabolites of the kynurenine (KYN) pathway of tryptophan (TRP) degradation have attracted interest as potential pathophysiological mediators and future diagnostic biomarkers. A greater knowledge of the pathological implications of the metabolites is associated with a need for a better understanding of how the normal behaviour and physiological activities impact their concentrations. This study aimed to investigate whether fasting (FAST) and whole-body cold-water immersion (CWI) affect KYN pathway metabolites. Thirteen young women were randomly assigned to receive the 2-d FAST with two 10-min CWI on separate days (FAST-CWI), 2-d FAST without CWI (FAST-CON), 2-d two CWI on separate days without FAST (CON-CWI) or the 2-d usual diet without CWI (CON-CON) in a randomised crossover fashion. Changes in plasma concentrations of TRP, kynurenic acid (KYNA), 3-hydroxy-kynurenine (3-HK), picolinic acid (PIC), quinolinic acid (QUIN) and nicotinamide (NAA) were determined with ultra-performance liquid chromatography-tandem mass spectrometer. FAST-CWI and FAST-CON lowered TRP concentration (P < 0·05, ηp2 = 0·24), and increased concentrations of KYNA, 3-HK and PIC (P < 0·05, ηp2 = 0·21-0·71) with no additional effects of CWI. The ratio of PIC/QUIN increased after FAST-CWI and FAST-CON trials (P < 0·05) but with a blunted effect in the FAST-CWI trial (P < 0·05) compared with the FAST-CON trials (ηp2 = 0·67). Concentrations of QUIN and NAA were unaltered. This study demonstrated that fasting for 2 d considerably impacts the concentration of several metabolites in the KYN pathway. This should be considered when discussing the potential of KYN pathway metabolites as biomarkers.