Search

Cataracts are the major cause of blindness worldwide, largely resulting from aging and diabetes mellitus. Advanced glycation end products (AGEs) have been identified as major contributors in cataract formation because they alter lens protein structure and stability and induce covalent cross-linking, aggregation, and insolubilization of lens crystallins. We investigated the potential of the deglycating enzyme fructosamine-3-kinase (FN3K) in the disruption of AGEs in cataractous lenses. Macroscopic changes of equine lenses were evaluated after ex vivo intravitreal FN3K injection. The mechanical properties of an equine lens pair were evaluated after treatment with saline and FN3K. AGE-type autofluorescence (AF) was measured to assess the time-dependent effects of FN3K on glycolaldehyde-induced AGE-modified porcine lens fragments and to evaluate its actions on intact lenses after in vivo intravitreal FN3K injection of murine eyes. A potential immune response after injection was evaluated by analysis of IL-2, TNFα, and IFNγ using an ELISA kit. Dose- and time-dependent AF kinetics were analyzed on pooled human lens fragments. Furthermore, AF measurements and a time-lapse of macroscopic changes were performed on intact cataractous human eye lenses after incubation with an FN3K solution. At last, AF measurements were performed on cataractous human eyes after crossover topical treatment with either saline- or FN3K-containing drops. While the lenses of the equine FN3K-treated eyes appeared to be clear, the saline-treated lenses had a yellowish-brown color. Following FN3K treatment, color restoration could be observed within 30 min. The extension rate of the equine FN3K-treated lens was more than twice the extension rate of the saline-treated lens. FN3K treatment induced significant time-dependent decreases in AGE-related AF values in the AGE-modified porcine lens fragments. Furthermore, in vivo intravitreal FN3K injection of murine eyes significantly reduced AF values of the lenses. Treatment did not provoke a systemic immune response in mice. AF kinetics of FN3K-treated cataractous human lens suspensions revealed dose- and time-dependent decreases. Incubation of cataractous human eye lenses with FN3K resulted in a macroscopic lighter color of the cortex and a decrease in AF values. At last, crossover topical treatment of intact human eyes revealed a decrease in AF values during FN3K treatment, while showing no notable changes with saline. Our study suggests, for the first time, a potential additional role of FN3K as an alternative treatment for AGE-related cataracts. [ABSTRACT FROM AUTHOR]

Purpose: Apnea duration is dependent on three factors: oxygen storage, oxygen consumption, hypoxia and hypercapnia tolerance. While current literature focuses on maximal apneas to improve apnea duration, apnea trained individuals use timed-repeated submaximal apneas, called "O2 and CO2 tables". These tables claim to accommodate the body to cope with hypoxia and hypercapnia, respectively. The aim of this study was twofold. First, to investigate the determinants of maximal apnea duration in apnea novices. Second, to compare physiologic responses to maximal apneas, O2 and CO2 tables. Methods: After medical screening, lung function test and hemoglobin mass measurement, twenty-eight apnea novices performed three apnea protocols in random order: maximal apneas, O2 table and CO2 table. During apnea, peripheral oxygen saturation (SpO2), heart rate (HR), muscle (mTOI) and cerebral (cTOI) tissue oxygenation index were measured continuously. End-tidal carbon dioxide (EtCO2) was measured before and after apneas. Results: Larger lung volumes, higher resting cTOI and lower resting EtCO2 levels correlated with longer apnea durations. Maximal apneas induced greater decreases in SpO2 (− 16%) and cTOI (− 13%) than O2 (− 8%; − 8%) and CO2 tables (− 6%; − 6%), whereas changes in EtCO2, HR and mTOI did not differ between protocols. Conclusion: These results suggest that, in apnea novices, O2 and CO2 tables did not induce a more profound hypoxia and hypercapnia, but a similar reduction in oxygen consumption than maximal apneas. Therefore, apnea novices should mainly focus on maximal apneas to improve hypoxia and hypercapnia tolerance. The use of specific lung training protocols can help to increase oxygen storage capacity. [ABSTRACT FROM AUTHOR]

Carnosine (β-alanyl-L-histidine) and its methylated analogues anserine and balenine are highly concentrated endogenous dipeptides in mammalian skeletal muscle that are implicated in exercise performance. Balenine has a much better bioavailability and stability in human circulation upon acute ingestion, compared to carnosine and anserine. Therefore, ergogenic effects observed with acute carnosine and anserine supplementation may be even more pronounced with balenine. This study investigated whether acute balenine supplementation improves physical performance in four maximal and submaximal exercise modalities. A total of 20 healthy, active volunteers (14 males; six females) performed cycling sprints, maximal isometric contractions, a 4-km TT and 20-km TT following either preexercise placebo or 10 mg/kg of balenine ingestion. Physical, as well as mental performance, along with acid–base balance and glucose concentration were assessed. Balenine was unable to augment peak power (p =.3553), peak torque (p =.3169), time to complete the 4 km (p =.8566), nor 20 km time trial (p =.2660). None of the performances were correlated with plasma balenine or CN1 enzyme activity. In addition, no effect on pH, bicarbonate, and lactate was observed. Also, the supplement did not affect mental performance. In contrast, glucose remained higher during and after the 20 km time trial following balenine ingestion. In conclusion, these results overall indicate that the functionality of balenine does not fully resemble that of carnosine and anserine, since it was unable to elicit performance improvements with similar and even higher plasma concentrations. [ABSTRACT FROM AUTHOR]

Multiple intramuscular variables have been proposed to explain the high variability in resistance training induced muscle hypertrophy across humans. This study investigated if muscular androgen receptor (AR), estrogen receptor α (ERα) and β (ERβ) content and fiber capillarization are associated with fiber and whole‐muscle hypertrophy after chronic resistance training. Male (n = 11) and female (n = 10) resistance training novices (22.1 ± 2.2 years) trained their knee extensors 3×/week for 10 weeks. Vastus lateralis biopsies were taken at baseline and post the training period to determine changes in fiber type specific cross‐sectional area (CSA) and fiber capillarization by immunohistochemistry and, intramuscular AR, ERα and ERβ content by Western blotting. Vastus lateralis volume was quantified by MRI‐based 3D segmentation. Vastus lateralis muscle volume significantly increased over the training period (+7.22%; range: −1.82 to +18.8%, p < 0.0001) but no changes occurred in all fiber (+1.64%; range: −21 to +34%, p = 0.869), type I fiber (+1.33%; range: −24 to +41%, p = 0.952) and type II fiber CSA (+2.19%; range: −23 to +29%, p = 0.838). However, wide inter‐individual ranges were found. Resistance training increased the protein expression of ERα but not ERβ and AR, and the increase in ERα content was positively related to changes in fiber CSA. Only for the type II fibers, the baseline capillary‐to‐fiber‐perimeter index was positively related to type II fiber hypertrophy but not to whole muscle responsiveness. In conclusion, an upregulation of ERα content and an adequate initial fiber capillarization may be contributing factors implicated in muscle fiber hypertrophy responsiveness after chronic resistance training. [ABSTRACT FROM AUTHOR]

Carnosine, a naturally occurring dipeptide present in an omnivorous diet, has been shown to ameliorate the development of metabolic syndrome, type 2 diabetes and early- and advanced-stage diabetic nephropathy (Albrecht et al. 2017) in different rodent models. The physiological mechanisms of the protection by carnosine is presumably related to its anti-lipidemic, anti-hyperglycemic and anti-glycation actions. As anserine, its methylated analogue, is more bio-available in humans upon supplementation (Everaert et al. 2018) without affecting its functionality, it was now aimed to investigate the effect of oral supplementation with anserine on the development of severe diabetes and advanced diabetic nephropathy in BTBR ob/ob mice. Male and female BTBR ob/ob mice were either supplemented with 4mM carnosine or anserine in drinking water for 18 weeks and compared with non-supplemented BTBR ob/ob and wt/wt mice. Tissue carnosine and anserine levels were determined with HPLC and metabolic markers were determined in clinical lab of University Hospital UZ Ghent. Gastrocnemius carnosine and anserine levels were lower in male ob/ob vs. wt/wt mice, but were not affected by supplementation. Kidney carnosine and anserine levels were not different between ob/ob and wt/wt mice, but anserine levels were significantly higher in anserine-treated mice compared to non-treated ob/ob mice. The evolution of fasting blood glucose, fructosamine, triglycerides and cholesterol was not affected by the supplementation regimen. The area of the glomerular tuft and whole glomerulus was bigger in ob/ob vs. wt/wt mice, but not affected by supplementation. Based on the currently measured markers, it is suggested that chronic oral anserine supplementation is not able to attenuate the development of diabetes or diabetic nephropathy in the severe model of BTBR ob/ob mice. Further research will have to elucidate whether anserine can attenuate milder forms of metabolic syndrome or type 2 diabetes. Disclosure: I. Everaert: None. M. Hanssens: None. H.J. Baelde: None. W. Derave: None. Funding: Research Foundation - Flanders [ABSTRACT FROM AUTHOR]

The original version of this article unfortunately contained a mistake. The author "Shahid Baba" would like to include the middle name "P" in the online published article. [ABSTRACT FROM AUTHOR]

The wide variation in muscle fibre type distribution across individuals, along with the very different energy consumption rates in slow versus fast muscle fibres, suggests that muscle fibre typology contributes to inter‐individual differences in metabolic rate during exercise. However, this has been hard to demonstrate due to the gap between a single muscle fibre and full‐body exercises. We investigated the isolated effect of triceps surae muscle contraction velocity on whole‐body metabolic rate during cyclic contractions in individuals a priori selected for their predominantly slow (n = 11) or fast (n = 10) muscle fibre typology by means of proton magnetic resonance spectroscopy (1H‐MRS). Subsequently, we examined their whole‐body metabolic rate during walking and running at 2 m/s, exercises with comparable metabolic rates but distinct triceps surae muscle force and velocity demands (walking: low force, high velocity; running: high force, low velocity). Increasing triceps surae contraction velocity during cyclic contractions elevated net whole‐body metabolic rate for both typology groups. However, the slow group consumed substantially less net metabolic energy at the slowest contraction velocity, but the metabolic difference between groups diminished at faster velocities. Consistent with the more economic force production during slow contractions, the slow group exhibited lower metabolic rates than the fast group while running, whereas metabolic rates were similar during walking. These findings provide important insights into the influence of muscle fibre typology on whole‐body metabolic rate and emphasize the importance of considering muscle mechanical demands to understand muscle fibre typology related differences in whole‐body metabolic rates. Key points: Muscle fibre typology is often suggested to affect whole‐body metabolic rate, yet convincing in vivo evidence is lacking.Using isolated plantar flexor muscle contractions in individuals a priori selected for their predominantly slow or fast muscle fibre typology, we demonstrated that having predominantly slow muscle fibres provides a metabolic advantage during slow muscle contractions, but this benefit disappeared at faster contractions.We extended these results to full‐body exercises, where we demonstrated that higher proportions of slow fibres associated with better economy during running but not when walking.These findings provide important insights into the influence of muscle fibre typology on whole‐body metabolic rate and emphasize the importance of considering muscle mechanical demands to understand muscle fibre typology related differences in whole‐body metabolic rate. [ABSTRACT FROM AUTHOR]

Muscle typology is heterogeneous among national level football (soccer) players, but positional differences remain unclear. Furthermore, fast typology (FT) individuals fatigue more than slow typology (ST) individuals in lab conditions. Therefore, we investigated if muscle typology is different between playing positions and if the decay in high‐intensity activities from the first to the second half is larger in FT football players than in ST players. We estimated muscle typology in 147 male professional football players by measuring soleus and gastrocnemius muscle carnosine via proton magnetic resonance spectroscopy. Players were classified as ST, intermediate typology (IT) or FT and categorized as goalkeeper, center back, full back, midfielder, winger or forward. Across four seasons in‐game distances covered in multiple running speed, acceleration and deceleration zones were collected during the first and second half. We found no differences in muscle typology between positions (p = 0.412). FT players covered 10.9% more high acceleration distance (>3 m.s−2) in the first half than ST players (p = 0.021) and high acceleration distance decay was larger for FT players (−12.4%) than ST (−7.7%; p = 0.006) and IT players (−7.3%; p = 0.010). Moreover, the decline in distance covered in several high‐intensity zones tended to be larger in FT players (−11.2% high‐intensity >15 km.h−1; −12.7% high deceleration <−3 m.s−2; −11.5% medium acceleration 2‐3 m.s−2) than in ST players (−7.1% high‐intensity; −8.1% high deceleration; −8.1% medium acceleration; 0.05 < p < 0.1). In conclusion, possessing a particular muscle typology is not required to play any football position at the national level. However, there are indications that FT players might fatigue more toward the end of the game compared to ST players. [ABSTRACT FROM AUTHOR]

This study examined whether muscle typology (muscle fibre type composition) is related to maximal strength and whether it can explain the high inter-individual variability in number of repetitions to failure during resistance training. Ninety-five resistance training novices (57 males) were assessed for their maximal isometric knee extension strength and muscle typology. Muscle typology was estimated by measuring carnosine in the soleus, gastrocnemius and/or vastus lateralis using proton magnetic resonance spectroscopy. Forty-four subjects (22 males) performed dynamic strength tests (1RM) and 3 sets of leg extensions and curls to failure (60%1RM) to determine the association between muscle typology and (total) number of repetitions. Twenty-one subjects performed additional biceps curls and triceps extensions (60%1RM) to assess influence of exercise, 23 subjects performed additional leg extensions and curls at 80% and 40%1RM to evaluate influence of training load. There was a weak but significant relationship between muscle typology and maximal isometric strength (r = 0.22, p = 0.03) favouring the fast typology individuals. Slow and fast typology individuals did not differ in upper arm and upper leg 1RM. Total number of repetitions was related to muscle typology at 80% (r = −0.42; p = 0.04) and 60% (p = −0.44; p = 0.003) but not at 40%1RM. Slow typology individuals performed more repetitions to failure at 60%1RM in the leg extension (p = 0.03), leg curl (p = 0.01) and biceps curl (p = 0.02). In conclusion, muscle typology has a small contribution to maximal isometric strength but not dynamic strength and partly determines the number of repetitions to failure during resistance training. This insight can help individualizing resistance training prescriptions. Having a fast muscle typology is positively associated with maximal isometric strength delivery in resistance training novices. The muscle typology seems to be a determining characteristic in the number of repetitions that can be performed during resistance training as slow typology individuals perform significantly more repetitions to failure compared to fast typology individuals. This study indicates the importance for coaches to shift from using traditional load-repetition tables and 1RM prediction equations to individualized 1RM testing and training volume prescriptions. [ABSTRACT FROM AUTHOR]

Considerable inter‐individual heterogeneity exists in the muscular adaptations to resistance training. It has been proposed that fast‐twitch fibres are more sensitive to hypertrophic stimuli and thus that variation in muscle fibre type composition is a contributing factor to the magnitude of training response. This study investigated if the inter‐individual variability in resistance training adaptations is determined by muscle typology and if the most appropriate weekly training frequency depends on muscle typology. In strength‐training novices, 11 slow (ST) and 10 fast typology (FT) individuals were selected by measuring muscle carnosine with proton magnetic resonance spectroscopy. Participants trained both upper arm and leg muscles to failure at 60% of one‐repetition maximum (1RM) for 10 weeks, whereby one arm and leg trained 3×/week and the contralateral arm and leg 2×/week. Muscle volume (MRI‐based 3D segmentation), maximal dynamic strength (1RM) and fibre type‐specific cross‐sectional area (vastus lateralis biopsies) were evaluated. The training response for total muscle volume (+3 to +14%), fibre size (−19 to +22%) and strength (+17 to +47%) showed considerable inter‐individual variability, but these could not be attributed to differences in muscle typology. However, ST individuals performed a significantly higher training volume to gain these similar adaptations than FT individuals. The limb that trained 3×/week had generally more pronounced hypertrophy than the limb that trained 2×/week, and there was no interaction with muscle typology. In conclusion, muscle typology cannot explain the high variability in resistance training adaptations when training is performed to failure at 60% of 1RM. Key points: This study investigated the influence of muscle typology (muscle fibre type composition) on the variability in resistance training adaptations and on its role in the individualization of resistance training frequency.We demonstrate that an individual's muscle typology cannot explain the inter‐individual variability in resistance training‐induced increases in muscle volume, maximal dynamic strength and fibre cross‐sectional area when repetitions are performed to failure.Importantly, slow typology individuals performed a significantly higher training volume to obtain similar adaptations compared to fast typology individuals.Muscle typology does not determine the most appropriate resistance training frequency. However, regardless of muscle typology, an additional weekly training (3×/week vs. 2×/week) increases muscle hypertrophy but not maximal dynamic strength.These findings expand on our understanding of the underlying mechanisms for the large inter‐individual variability in resistance training adaptations. [ABSTRACT FROM AUTHOR]

Balenine possesses some of carnosine's and anserine's functions, yet it appears more resistant to the hydrolysing CN1 enzyme. The aim of this study was to elucidate the stability of balenine in the systemic circulation and its bioavailability in humans following acute supplementation. Two experiments were conducted in which (in vitro) carnosine, anserine and balenine were added to plasma to compare degradation profiles and (in vivo) three increasing doses (1–4–10 mg/kg) of balenine were acutely administered to 6 human volunteers. Half-life of balenine (34.9 ± 14.6 min) was respectively 29.1 and 16.3 times longer than that of carnosine (1.20 ± 0.36 min, p = 0.0044) and anserine (2.14 ± 0.58 min, p = 0.0044). In vivo, 10 mg/kg of balenine elicited a peak plasma concentration (Cmax) of 28 µM, which was 4 and 18 times higher than with 4 (p = 0.0034) and 1 mg/kg (p = 0.0017), respectively. CN1 activity showed strong negative correlations with half-life (ρ = − 0.829; p = 0.0583), Cmax (r = − 0.938; p = 0.0372) and incremental area under the curve (r = − 0.825; p = 0.0433). Overall, balenine seems more resistant to CN1 hydrolysis resulting in better in vivo bioavailability, yet its degradation remains dependent on enzyme activity. Although a similar functionality as carnosine and anserine remains to be demonstrated, opportunities arise for balenine as nutraceutical or ergogenic aid. [ABSTRACT FROM AUTHOR]

Exercise profoundly influences glycemic control by enhancing muscle insulin sensitivity, thus promoting glucometabolic health. While prior glycogen breakdown so far has been deemed integral for muscle insulin sensitivity to be potentiated by exercise, the mechanisms underlying this phenomenon remain enigmatic. We have combined original data from 13 of our studies that investigated insulin action in skeletal muscle either under rested conditions or following a bout of one-legged knee extensor exercise in healthy young male individuals (n = 106). Insulin-stimulated glucose uptake was potentiated and occurred substantially faster in the prior contracted muscles. In this otherwise homogenous group of individuals, a remarkable biological diversity in the glucometabolic responses to insulin is apparent both in skeletal muscle and at the whole-body level. In contrast to the prevailing concept, our analyses reveal that insulin-stimulated muscle glucose uptake and the potentiation thereof by exercise are not associated with muscle glycogen synthase activity, muscle glycogen content, or degree of glycogen utilization during the preceding exercise bout. Our data further suggest that the phenomenon of improved insulin sensitivity in prior contracted muscle is not regulated in a homeostatic feedback manner from glycogen. Instead, we put forward the idea that this phenomenon is regulated by cellular allostatic mechanisms that elevate the muscle glycogen storage set point and enhance insulin sensitivity to promote the uptake of glucose toward faster glycogen resynthesis without development of glucose overload/toxicity or feedback inhibition. [ABSTRACT FROM AUTHOR]

Diabetic nephropathy (DN) is a major cause of global kidney failure. While histological kidney biopsy is the gold standard for diagnosis, it primarily reveals tissue morphology. In contrast, near-infrared (NIR) microscopy offers a label-free method for detailed molecular characterization of kidney tissue. Hematoxylin and eosin-stained kidney tissue samples from 17 ob/ob mice with DN and 14 healthy mice were examined using Fourier transform-NIR microscopy. Four different spectra were obtained from both the mesangium and tubulus. NIR spectral analysis unveiled distinct differences in wavenumbers between DN-affected and healthy kidneys, notably in the carbohydrate and protein-associated region (5500-4200 cm−1). In the mesangium, DN tissue samples exhibited higher median values at 4235 cm−1, 4659 cm−1, 4844 cm−1, 4906 cm−1, and 5222 cm−1 compared to controls (P < 0.05, P < 0.01, P < 0.05, P < 0.05 and P < 0.001, respectively). In tubular spectra, higher median values were found at 4258 cm−1, 4659 cm−1, 5222 cm−1, and 5346 cm−1 in the DN group (P < 0.01, P < 0.05, P < 0.05 and P < 0.01, respectively). These spectral differences strongly correlated with metabolic, histologic, and urinary parameters, providing valuable DN progression insights. The classification model achieved a visible clustering between the control and DN group for both the mesangial and tubular measurements. NIR microscopy demonstrated significant spectral differences between DN and healthy kidney tissues in mice, hinting at its potential for providing chemical insights, aiding in more accurate diagnoses, and offering a foundation for further clinical exploration and potential therapeutic advancements in DN. [Display omitted] • NIR microscopy distinctively identifies diabetic nephropathy in ob / ob mice. • Significant spectral differences in kidneys affected by diabetic nephropathy. • Strong correlations with metabolic and histological parameters. • Potential of NIR microscopy for detailed molecular insights in kidney tissues. • Capability of NIR microscopy in enhancing diabetic nephropathy research. [ABSTRACT FROM AUTHOR]

Purpose: A simple ankle-foot exoskeleton that assists plantarflexion during push-off can reduce the metabolic power during walking. This suggests that walking performance during a maximal incremental exercise could be improved with an exoskeleton if the exoskeleton is still efficient during maximal exercise intensities. Therefore, we quantified the walking performance during a maximal incremental exercise test with a powered and unpowered exoskeleton: uphill walking with progressively higher weights. Methods: Nine female subjects performed two incremental exercise tests with an exoskeleton: 1 day with (powered condition) and another day without (unpowered condition) plantarflexion assistance. Subjects walked on an inclined treadmill (15 %) at 5 km h and 5 % of body weight was added every 3 min until exhaustion. Results: At volitional termination no significant differences were found between the powered and unpowered condition for blood lactate concentration (respectively, 7.93 ± 2.49; 8.14 ± 2.24 mmol L), heart rate (respectively, 190.00 ± 6.50; 191.78 ± 6.50 bpm), Borg score (respectively, 18.57 ± 0.79; 18.93 ± 0.73) and $$\dot{V}{\rm O}_{2}$$ peak (respectively, 40.55 ± 2.78; 40.55 ± 3.05 ml min kg). Thus, subjects were able to reach the same (near) maximal effort in both conditions. However, subjects continued the exercise test longer in the powered condition and carried 7.07 ± 3.34 kg more weight because of the assistance of the exoskeleton. Conclusion: Our results show that plantarflexion assistance during push-off can increase walking performance during a maximal exercise test as subjects were able to carry more weight. This emphasizes the importance of acting on the ankle joint in assistive devices and the potential of simple ankle-foot exoskeletons for reducing metabolic power and increasing weight carrying capability, even during maximal intensities. [ABSTRACT FROM AUTHOR]

Background: Hamstring strain injuries (HSI) are prevalent in team sports and occur frequently in the later phase of matches. In the search for interindividual factors that determine muscle fatigue and possibly injury risk, muscle fibre typology is a likely candidate. Objective: The aim of the study was to determine whether muscle fibre typology is a risk factor for HSI. Methods: A prospective cohort study was conducted over three seasons in professional football players competing in the Belgian Jupiler Pro League (n = 118) and in the English Premier League (n = 47). A total of 27 HSI were sustained during this period. Muscle fibre typology was non-invasively estimated using proton magnetic resonance spectroscopy and was characterized as a fast, slow, or intermediate typology based on the carnosine concentration in the soleus. A multivariate Cox model was used to identify risk factors for HSI. Results: Football players exhibited a wide variety of muscle typologies (slow 44.9%, intermediate 39.8%, fast 15.3%). In the combined cohort, players with a fast typology displayed a 5.3-fold (95% confidence interval [CI] 1.92–14.8; P = 0.001) higher risk of sustaining an index HSI than slow typology players. This was also independently observed in both leagues separately as, respectively, a 6.7-fold (95% CI 1.3–34.1; P = 0.023) and a 5.1-fold (95% CI 1.2–20.4; P = 0.023) higher chance was found in fast typology players than in slow typology players of the Jupiler Pro League and the Premier League cohort. Conclusion: We identified muscle fibre typology as a novel and potent risk factor for HSI in team sports. [ABSTRACT FROM AUTHOR]

Background: Multiple sclerosis (MS) is a chronic autoimmune disease driven by sustained inflammation in the central nervous system. One of the pathological hallmarks of MS is extensive free radical production. However, the subsequent generation, potential pathological role, and detoxification of different lipid peroxidation-derived reactive carbonyl species during neuroinflammation are unclear, as are the therapeutic benefits of carbonyl quenchers. Here, we investigated the reactive carbonyl acrolein and (the therapeutic effect of) acrolein quenching by carnosine during neuroinflammation.Methods: The abundance and localization of acrolein was investigated in inflammatory lesions of MS patients and experimental autoimmune encephalomyelitis (EAE) mice. In addition, we analysed carnosine levels and acrolein quenching by endogenous and exogenous carnosine in EAE. Finally, the therapeutic effect of exogenous carnosine was assessed in vivo (EAE) and in vitro (primary mouse microglia, macrophages, astrocytes).Results: Acrolein was substantially increased in inflammatory lesions of MS patients and EAE mice. Levels of the dipeptide carnosine (β-alanyl-L-histidine), an endogenous carbonyl quencher particularly reactive towards acrolein, and the carnosine-acrolein adduct (carnosine-propanal) were ~ twofold lower within EAE spinal cord tissue. Oral carnosine treatment augmented spinal cord carnosine levels (up to > tenfold), increased carnosine-acrolein quenching, reduced acrolein-protein adduct formation, suppressed inflammatory activity, and alleviated clinical disease severity in EAE. In vivo and in vitro studies indicate that pro-inflammatory microglia/macrophages generate acrolein, which can be efficiently quenched by increasing carnosine availability, resulting in suppressed inflammatory activity. Other properties of carnosine (antioxidant, nitric oxide scavenging) may also contribute to the therapeutic effects.Conclusions: Our results identify carbonyl (particularly acrolein) quenching by carnosine as a therapeutic strategy to counter inflammation and macromolecular damage in MS. [ABSTRACT FROM AUTHOR]

Muscle weakness and fatigue are primary manifestations of multiple sclerosis (MS), a chronic disease of the central nervous system. Interventions that enhance muscle function may improve overall physical well-being of MS patients. Recently, we described that levels of carnosine, an endogenous muscle dipeptide involved in contractile function and fatigue-resistance, are reduced in muscle tissue from MS patients and a monophasic rodent MS model (experimental autoimmune encephalomyelitis, EAE). In the present study, we aimed to (1) confirm this finding in a chronic EAE model, along with the characterization of structural and functional muscle alterations, and (2) investigate the effect of carnosine supplementation to increase/restore muscle carnosine levels and improve muscle function in EAE. We performed muscle immunohistochemistry and ex vivo contractility measurements to examine muscle structure and function at different stages of EAE, and following nutritional intervention (oral carnosine: 3, 15 or 30 g/L in drinking water). Immunohistochemistry revealed progressively worsening muscle fiber atrophy and a switch towards a fast-twitch muscle phenotype during EAE. Using ex vivo muscle contractility experiments, we observed reductions in muscle strength and contraction speed, but no changes in muscle fatigability of EAE mice. However, carnosine levels were unaltered during all stages of EAE, and even though oral carnosine supplementation dose-dependently increased muscle carnosine levels up to + 94% after 56 days EAE, this did not improve muscle function of EAE mice. In conclusion, EAE mice display significant, yet time-dependent, muscular alterations, and carnosine intervention does not improve muscle function in EAE. [ABSTRACT FROM AUTHOR]

Purpose: The aims of this study were 1) to model the temporal profile of W' recovery after exhaustion, 2) to estimate the contribution of changing ...O2 kinetics to this recovery, and 3) to examine associations with aerobic fitness and muscle fiber type (MFT) distribution. Methods: Twenty-one men (age = 25 ± 2 yr, ...O2peak = 54.4 ± 5.3 mL⋅min-1⋅kg-1) performed several constant load tests to determine critical power and W' followed by eight trials to quantify W' recovery. Each test consisted of two identical exhaustive work bouts (WB1 and WB2), separated by a variable recovery interval of 30, 60, 120, 180, 240, 300, 600, or 900 s. Gas exchange was measured and muscle biopsies were collected to determine MFT distribution. W' recovery was quantified as observed W' recovery (W'OBS), model-predicted W' recovery (W'BAL), and W' recovery corrected for changing ...O2 kinetics (W'ADJ). W'OBS and W'ADJ were modeled using mono- and biexponential fitting. Root-mean-square error (RMSE) and Akaike information criterion (ΔAICC) were used to evaluate the models' accuracy. Results: The W'BAL model (τ = 524 ± 41 s) was associated with an RMSE of 18.6% in fitting W'OBS and underestimated W' recovery for all durations below 5 min (P < 0.002). Monoexponential modeling of W'OBS resulted in τ = 104 s with RMSE = 6.4%. Biexponential modeling of W'OBS resulted in τ1 = 11 s and τ2 = 256 s with RMSE = 1.7%. W'ADJ was 11% ± 1.5% lower than W'OBS (P < 0.001). ΔAICC scores favored the biexponential model for W'OBS, but not for W'ADJ. ...O2peak (P = 0.009) but not MFT distribution (P = 0.303) was associated with W'OBS. Conclusion: We showed that W' recovery from exhaustion follows a two-phase exponential time course that is dependent on aerobic fitness. The appearance of a fast initial recovery phase was attributed to an enhanced aerobic energy provision resulting from changes in ...O2 kinetics. [ABSTRACT FROM AUTHOR]

Carnosine, a naturally occurring dipeptide present in an omnivorous diet, has been shown to ameliorate the development of metabolic syndrome, type-2 diabetes (T2D) and early- and advanced-stage diabetic nephropathy in different rodent models. Anserine, its methylated analogue, is more bio-available in humans upon supplementation without affecting its functionality. In this work, we investigated the effect of oral supplementation with anserine or carnosine on circulating and tissue anserine and carnosine levels and on the development of T2D and diabetic nephropathy in BTBR ob/ob mice. BTBR ob/ob mice were either supplemented with carnosine or anserine in drinking water (4 mM) for 18 weeks and compared with non-supplemented BTBR ob/ob and wild-type (WT) mice. Circulating and kidney, but not muscle, carnosine, and anserine levels were enhanced by supplementation with the respective dipeptides in ob/ob mice compared to non-treated ob/ob mice. The evolution of fasting blood glucose, insulin, fructosamine, triglycerides, and cholesterol was not affected by the supplementation regimens. The albumin/creatine ratio, glomerular hypertrophy, and mesangial matrix expansion were aggravated in ob/ob vs. WT mice, but not alleviated by supplementation. To conclude, long-term supplementation with anserine elevates circulating and kidney anserine levels in diabetic mice. However, anserine supplementation was not able to attenuate the development of T2D or diabetic nephropathy in BTBR ob/ob mice. Further research will have to elucidate whether anserine can attenuate milder forms of T2D or metabolic syndrome. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to identify the relationships between lower limb muscle characteristics and mechanical variables derived from the vertical (jumping) and horizontal (sprinting) force-- velocity--power (FVP) profiles. Methods: Nineteen subelite male rugby league players performed a series of squat jumps and linear 30-m sprints to derive the vertical and horizontal FVP profiles, respectively. The theoretical maximal force (F0), velocity (V0), and power (Pmax) were derived from both the vertical (i.e., vF0, vV0, and vPmax) and the horizontal (i.e., hF0, hV0, and hPmax) FVP profiles. Vastus lateralis (VL), biceps femoris long head, and gastrocnemius medialis (GM) and lateralis muscle fascicle length, pennation angle, and thickness were measured using B-mode ultrasonography.Magnetic resonance imaging was used to calculate volumes of major lower limb muscles, whereas proton magnetic resonance spectroscopy was used to quantify the carnosine content of the GM to estimate muscle fiber typology. Results: Variation in vPmax was best explained by GM muscle fiber typology (i.e., greater estimated proportion of Type II fibers) and VL volume (adjusted r² = 0.440, P = 0.006), whereas adductor and vastus medialis volume and GM muscle fiber typology explained the most variation in hPmax (adjusted r² = 0.634, P = 0.032). Rectus femoris and VL volume explained variation in vF0 (r² = 0.430, P = 0.008), whereas adductor and vastus medialis volume explained variation in hF0 (r² = 0.432, P = 0.007). Variations in vV0 and hV0 were best explained by GM muscle fiber typology (adjusted r² = 0.580, P < 0.001) and GM muscle fiber typology and biceps femoris short head volume (adjusted r² = 0.590, P < 0.001), respectively. Conclusion: Muscle fiber typology and muscle volume are strong determinants of maximal muscle power in jumping and sprinting by influencing the velocity- and force-oriented mechanical variables. [ABSTRACT FROM AUTHOR]

Oligodendrocyte precursor cells (OPCs) account for 5% of the resident parenchymal central nervous system glial cells. OPCs are not only a back-up for the loss of oligodendrocytes that occurs due to brain injury or inflammation-induced demyelination (remyelination) but are also pivotal in plastic processes such as learning and memory (adaptive myelination). OPC differentiation into mature myelinating oligodendrocytes is controlled by a complex transcriptional network and depends on high metabolic and mitochondrial demand. Mounting evidence shows that OPC dysfunction, culminating in the lack of OPC differentiation, mediates the progression of neurodegenerative disorders such as multiple sclerosis, Alzheimer's disease and Parkinson's disease. Importantly, neurodegeneration is characterised by oxidative and carbonyl stress, which may primarily affect OPC plasticity due to the high metabolic demand and a limited antioxidant capacity associated with this cell type. The underlying mechanisms of how oxidative/carbonyl stress disrupt OPC differentiation remain enigmatic and a focus of current research efforts. This review proposes a role for oxidative/carbonyl stress in interfering with the transcriptional and metabolic changes required for OPC differentiation. In particular, oligodendrocyte (epi)genetics, cellular defence and repair responses, mitochondrial signalling and respiration, and lipid metabolism represent key mechanisms how oxidative/carbonyl stress may hamper OPC differentiation in neurodegenerative disorders. Understanding how oxidative/carbonyl stress impacts OPC function may pave the way for future OPC-targeted treatment strategies in neurodegenerative disorders. [ABSTRACT FROM AUTHOR]

Purpose: Chronic β-alanine supplementation leads to increased levels of muscle histidine-containing dipeptides. However, the majority of ingested β-alanine is, most likely, degraded by two transaminases: GABA-T and AGXT2. In contrast to GABA-T, the in vivo role of AGXT2 with respect to β-alanine metabolism is unknown. The purpose of the present work is to investigate if AGXT2 is functionally involved in β-alanine homeostasis. Methods: Muscle histidine-containing dipeptides levels were determined in AGXT2 overexpressing or knock-out mice and in human subjects with different rs37369 genotypes which is known to affect AGXT2 activity. Further, plasma β-alanine kinetic was measured and urine was obtained from subjects with different rs37369 genotypes following ingestion of 1400 mg β-alanine. Result: Overexpression of AGXT2 decreased circulating and muscle histidine-containing dipeptides (> 70% decrease; p < 0.05), while AGXT2 KO did not result in altered histidine-containing dipeptides levels. In both models, β-alanine remained unaffected in the circulation and in muscle (p > 0.05). In humans, the results support the evidence that decreased AGXT2 activity is not associated with altered histidine-containing dipeptides levels (p > 0.05). Additionally, following an acute dose of β-alanine, no differences in pharmacokinetic response were measured between subjects with different rs37369 genotypes (p > 0.05). Interestingly, urinary β-alanine excretion was 103% higher in subjects associated with lower AGXT2 activity, compared to subjects associated with normal AGXT2 activity (p < 0.05). Conclusion: The data suggest that in vivo, β-alanine is a substrate of AGXT2; however, its importance in the metabolism of β-alanine and histidine-containing dipeptides seems small. [ABSTRACT FROM AUTHOR]

Multiple sclerosis (MS) pathology features autoimmune-driven neuroinflammation, demyelination, and failed remyelination. Carnosine is a histidine-containing dipeptide (HCD) with pluripotent homeostatic properties that is able to improve outcomes in an animal MS model (EAE) when supplied exogenously. To uncover if endogenous carnosine is involved in, and protects against, MS-related neuroinflammation, demyelination or remyelination failure, we here studied the HCD-synthesizing enzyme carnosine synthase (CARNS1) in human MS lesions and two preclinical mouse MS models (EAE, cuprizone). We demonstrate that due to its presence in oligodendrocytes, CARNS1 expression is diminished in demyelinated MS lesions and mouse models mimicking demyelination/inflammation, but returns upon remyelination. Carns1 -KO mice that are devoid of endogenous HCDs display exaggerated neuroinflammation and clinical symptoms during EAE, which could be partially rescued by exogenous carnosine treatment. Worsening of the disease appears to be driven by a central, not peripheral immune-modulatory, mechanism possibly linked to impaired clearance of the reactive carbonyl acrolein in Carns1 -KO mice. In contrast, CARNS1 is not required for normal oligodendrocyte precursor cell differentiation and (re)myelin to occur, and neither endogenous nor exogenous HCDs protect against cuprizone-induced demyelination. In conclusion, the loss of CARNS1 from demyelinated MS lesions can aggravate disease progression through weakening the endogenous protection against neuroinflammation. • CARNS1 is expressed by oligodendrocytes and is diminished in demyelinated MS lesions and mouse MS models. • Carns1 -KO mice display exaggerated neuroinflammation during EAE, which is partially rescued by exogenous carnosine treatment. • CNS-intrinsic mechanisms, such as an impaired clearance of acrolein, may aggravate neuroinflammation in Carns1 -KO mice. • CARNS1 and HCDs do not protect against demyelination and are not required for normal OPC differentiation and (re)myelination. [ABSTRACT FROM AUTHOR]

Describes some factors affecting glucose utilization during exercise in skeletal muscle. Glucose utilization and glucose transporters expression; Effects of endurance training; Signaling in exercise-induced glucose transport.

• This study examined the effect of eight weeks of apnea training. • 8 weeks of apnea training increases maximal apnea time by 41% in novice subjects. • 8 weeks of apnea training is not sufficient to enhance acute responses to apnea. • Spleen volumes however, can be increased through apnea training. Splenic contraction is an important response to acute apnea causing the release of red blood cells into blood circulation. Current literature shows higher spleen volumes and greater spleen contractions in trained apnea divers compared to untrained individuals, but the influence of training is presently unknown. Thirteen subjects daily performed five static apneas for 8 weeks. Before, halfway through and after the apnea training period, subjects performed five maximal breath-holds at the laboratory. Baseline values for and changes in splenic volume and hemoglobin ([Hb]) were assessed. Although baseline spleen volume had increased (from 241 ± 55 mL PRE to 299 ± 51 mL POST training, p = 0.007), the absolute spleen contraction (142 ± 52 mL PRE and 139 ± 34 mL POST training, p = 0.868) and the acute increase in [Hb] remained unchanged. The present study shows that apnea training can increase the size of the spleen but that eight weeks of training is not sufficient to elicit significant training adaptations on the acute response. [ABSTRACT FROM AUTHOR]

Supplemental digital content is available in the text. Purpose: Recent observations demonstrate that a sizeable proportion of the recreational running population runs at rather slow speeds and does not always show a clear flight phase. This study determined the key biomechanical and physiological characteristics of this running pattern, i.e., grounded running (GR), and compared these characteristics with slow aerial running (SAR) and reference data on walking at the same slow running speed. Methods: Thirty male subjects performed instructed GR and SAR at 2.10 m·s−1 on a treadmill. Ground reaction forces, tibial accelerations, and metabolic rate were measured to estimate general musculoskeletal loading (external power and maximal vertical ground reaction force), impact intensity (vertical instantaneous loading rate and tibial acceleration), and energy expenditure. More explicit measures of muscular loading (muscle stresses and peak eccentric power) were calculated based on a representative subsample, in which detailed kinematics and kinetics were recorded. We hypothesized that all measures would be lower for the GR condition. Results: Subjects successfully altered their running pattern upon a simple instruction toward a GR pattern by increasing their duty factor from 41.5% to 51.2%. As hypothesized, impact intensity, general measures for musculoskeletal, and the more explicit measures for muscular loading decreased by up to 35.0%, 20.3%, and 34.0%, respectively, compared with SAR. Contrary to our hypothesis, metabolic rate showed an increase of 4.8%. Conclusions: Changing running style from SAR to GR reduces musculoskeletal loading without lowering the metabolic energy requirements. As such, GR might be beneficial for most runners as it has the potential to reduce the risk of running-related injuries while remaining a moderate to vigorous form of physical activity, contributing to fulfillment of the recommendations concerning physical activity and public health. [ABSTRACT FROM AUTHOR]

Carnosine (beta-alanyl-L-histidine) and its methylated analogue anserine are present in relevant concentrations in the omnivore human diet. Several studies reported promising therapeutic potential for carnosine in various rodent models of oxidative stress and inflammation-related chronic diseases. Nevertheless, the poor serum stability of carnosine in humans makes the translation of rodent models hard. Even though anserine and carnosine have similar biochemical properties, anserine has better serum stability. Despite this interesting profile, the research on anserine is scarce. The aim of this study was to explore the bioavailability and stability of synthesized anserine by (1) performing in vitro stability experiments in human plasma and molecular modelling studies and by (2) evaluating the plasma and urinary pharmacokinetic profile in healthy volunteers following different doses of anserine (4-10-20 mg/kg body weight). A bio-analytical method for measuring anserine levels was developed and validated using liquid chromatography-electrospray mass spectrometry. Both plasma (CMAX: 0.54-1.10-3.12 µM) and urinary (CMAX: 0.09-0.41-0.72 mg/mg creatinine) anserine increased dose-dependently following ingestion of 4-10-20 anserine mg/kg BW, respectively. The inter-individual variation in plasma anserine was mainly explained by the activity (R2 = 0.75) and content (R2 = 0.77) of the enzyme serum carnosinase-1. Compared to carnosine, a lower interaction energy of anserine with carnosinase-1 was suggested by molecular modelling studies. Conversely, the two dipeptides seems to have similar interaction with the PEPT1 transporter. It can be concluded that nutritionally relevant doses of synthesized anserine are well-absorbed and that its degradation by serum carnosinase-1 is less pronounced compared to carnosine. This makes anserine a good candidate as a more stable carnosine-analogue to attenuate chronic diseases in humans. [ABSTRACT FROM AUTHOR]

Purpose: Carnosine is a dipeptide composed of β-alanine and L-histidine and is present in skeletal muscle. Chronic oral β-alanine supplementation can induce muscle carnosine loading and is therefore seen as the rate-limiting factor for carnosine synthesis. However, the effect of L-histidine supplementation on carnosine levels in humans is never established. This study aims to investigate whether 1) L-histidine supplementation can induce muscle carnosine loading and 2) combined supplementation of both amino acids is more efficient than A-alanine supplementation alone. Methods: Fifteen male and 15 female participants were equally divided in three groups. Each group was supplemented with either pure β-alanine (BA) (6 g⋅d-1), L-histidine (HIS) (3.5 g⋅d-1), or both amino acids (BA + HIS). Before (D0), after 12 d (D12), and after 23 d (D23) of supplementation, carnosine content was evaluated in soleus and gastrocnemius medialis muscles by ¹H-MRS, and venous blood samples were collected. Muscle biopsies were taken at D0 and D23 from the vastus lateralis. Plasma and muscle metabolites (β-alanine, histidine, and carnosine) were measured by high-performance liquid chromatography. Results: Both BA and BA + HIS groups showed increased carnosine concentrations in all investigated muscles, with no difference between these groups. By contrast, carnosine levels in the HIS group remained unaltered. Histidine levels were significantly decreased in plasma (-30.6%) and muscle (-31.6%) of the BA group, and this was prevented when β-alanine and L-histidine were supplemented simultaneously. Conclusion: We confirm that β-alanine, and not L-histidine, is the rate-limiting precursor for carnosine synthesis in human skeletal muscle. Yet, although L-histidine is not rate limiting, its availability is not unlimited and gradually declines upon chronic β-alanine supplementation. The significance of this decline still needs to be determined, but may affect physiological processes such as protein synthesis. [ABSTRACT FROM AUTHOR]

The influence of subcutaneous adipose tissue (ATT) and oxygen (O2) delivery has been poorly defined in frequency domain (FD) near-infrared spectroscopy (NIRS). Therefore, the aim of this study was to investigate the possible influence of these variables on all FD NIRS responses using a reliable protocol. Moreover, these influences were also investigated when using relative oxy- and deoxyhemoglobin and -myoglobin (oxy[Hb+Mb] and deoxy[Hb+Mb]) values (in %). A regression analysis was carried out for ATT and maximal-minimum oxy[Hb+Mb], deoxy[Hb+Mb], oxygen saturation (SmO2), and total hemoglobin (totHb) amplitudes during an incremental cyclic contraction protocol (ICCP) in a group of 45 participants. Moreover, the same analysis was carried out between subcutaneous ATT and the relative oxy- and deoxy[Hb+Mb] values (in %). In the second part of this study, a regression analysis was performed for peak forearm blood flow (FBF) during ICCP and the absolute and relative NIRS values in a group of 37 participants. Significant exponential correlation coefficients were found between ATT and deoxy[Hb+Mb] (r=0.53; P<0.001), oxy[Hb+Mb] (r=0.57; P<0.001), and SmO2 amplitudes (r=0.57; P<0.001). No significant relations were found between ATTand relative oxy[Hb+Mb] (r=0.37; P=0.07) and deoxy[Hb+Mb] (r=0.09; P=0.82). Significant positive correlation coefficients were found between force at exhaustion and maximal FBF (r=0.66; P<0.001), maximal differences in deoxy[Hb+Mb] (r=0.353; P=0.032) and totHb (r=0.512; P=0.002) while no significant correlation coefficients were found between these maximal force values and maximal differences in oxy[Hb+Mb] (r=-0.267; P=0.111) and SmO2 (r=-0.267; P=0.111). Significant linear correlation coefficients were found between FBF and deoxy[Hb+Mb] (r=0.51; P=0.001), oxy[Hb+Mb] (r=-0.50; P=0.001), SmO2 (r=-0.54; P=0.001), and totHb amplitude (r=0.61; P<0.001). No significant correlations were found when using relative oxy[Hb+Mb] (r=-0.01; P=0.957) and deoxy[Hb+Mb] (r=-0.02; P=0.895). Based on these findings, caution is advised when using NIRS values, as subcutaneous ATT and O2 delivery significantly influence NIRS measurements. To eliminate these influences, use of relative deoxy[Hb+Mb] is advised, especially in clinical settings or in people with a higher subcutaneous ATT layer. [ABSTRACT FROM AUTHOR]

Introduction: Beta- alanine (BA) is a popular ergogenic supplement because it can induce muscle camosine loading. We hypothesize that, by analogy with creatine supplementation, 1) an inverse relationship between urinary excretion and muscle loading is present, and 2) the latter is stimulated by carbohydrate- and protein-induced insulin action. Methods: hi study A, the effect of a 5-wk slow-release BA (SRBA) supplementation (4.8 g⋅d-1) on whole body BA retention was determined in seven men. We further determined whether the coingestion of carbohydrates and proteins with SRBA would improve retention. In study B (34 subjects), we explored the effect of meal timing on muscle camosine loading (3.2 g⋅d-1 during 6-7 wk). One group received pure BA (PBA) in between the meals; the other received PBA at the start of the meals, to explore the effect of meal-induced insulin release. Further, we compared with a third group receiving SRBA at the start of the meals. Results and Conclusion: Orally ingested SRBA has a very high whole body retention (97%-98%) that is not declining throughout the 5-wk supplementation period, nor is it influenced by the coingestion of macronutrients. Thus, a very small portion ( 1 %-2%) is lost through urinary excretion, and equally only a small portion is incorporated into muscle camosine (3%), indicating that most ingested BA is metabolized (possibly through oxidation). Second, in soleus muscles, the efficiency of camosine loading is significantly higher when PBA is coingested with a meal (+64%) compared with in between the meals (+41%), suggesting that insulin stimulates muscle camosine loading. Finally, the chronic supplementation of SRBA versus PBA seems equally effective [ABSTRACT FROM AUTHOR]

The article reports on research which was conducted to investigate the effect long-term supplementation with increasing doses of camosine and beta-alanine had on muscle camosine, anserine, and taurine levels and on in vitro contractility and fatigue in mice. Researchers evaluated 66 male Naval Medical Research Institute mice who were control fed or supplemented with either camosine or beta-alanine in their drinking water for 8-12 weeks. They found that beta-alanine availability seemed to be the rate-limiting step for synthesis of muscle histidine-containing dipeptides in mice and that muscle histidine-containing dipeptide loading in mice moderately and muscle dependently affected excitation-contraction coupling and fatigue.

The dipeptide carnosine is found in high concentrations in human skeletal muscle and shows large inter-individual differences. Sex and age are determining factors, however, systematic studies investigating the sex effects on muscle carnosine content throughout the human lifespan are lacking. Despite the large inter-individual variation, the intra-individual variation is limited. The question may be asked whether the carnosine content is a muscle characteristic which may be largely genetically determined. A total of 263 healthy male and female subjects of 9-83 years were divided into five different age groups: prepubertal children (PC), adolescents (A), young adults (YA), middle adults (MA) and elderly (E). We included 25 monozygotic and 22 dizygotic twin pairs among the entire study population to study the heritability. The carnosine content was measured non-invasively in the gastrocnemius medialis and soleus by proton magnetic resonance spectroscopy (H-MRS). In boys, carnosine content was significantly higher (gastrocnemius 22.9%; soleus 44.6%) in A compared to PC, while it did not differ in girls. A decrease (~16%) was observed both in males and females from YA to MA. However, elderly did not have lower carnosine levels in comparison with MA. Higher correlations were found in monozygotic ( r = 0.86) compared to dizygotic ( r = 0.51) twins, in soleus muscle, but not in gastrocnemius. In conclusion, this study found an effect of puberty on muscle carnosine content in males, but not in females. Muscle carnosine decreased mainly during early adulthood and hardly from adulthood to elderly. High intra-twin correlations were observed, but muscle-dependent differences preclude clear conclusions toward heritability. [ABSTRACT FROM AUTHOR]

Background. Although health-related benefits of fitness training in older men are well established, it is not clear yet which mode and intensity of a exercise program is most effective. This study addresses whether the combination of endurance (ED) and resistance training in older men have supplementary health-related benefits in addition to profits attained through endurance training alone. Additionally, effects of moderate- and low-intensity resistance training are compared.Methods. Men, 55–75 years of age, were randomly assigned to a control group (N = 13) or one of three exercise groups (20 weeks, two to three times per week): endurance plus moderate resistance (MR) training (N = 22), endurance plus low resistance (LR) training (N = 22) and endurance training only (N = 22). Cardiovascular (CV) risk factors, muscular fitness and postural control were assessed before and after training.Results. All exercise groups revealed significant (P < 0.05) improvements in resting heart rate, work capacity and recovery, waist girth, insulin response and knee-extensor strength with no differences among groups. Body composition, resting metabolic rate (RMR), VO2peak and postural control did not change in exercise groups.Conclusion. In older men, a fitness program consisting of 20 weeks endurance training combined with resistance training is equally effective as endurance training alone. Moderate vs. low resistance training added to endurance training yields similar health-related benefits. [Copyright &y& Elsevier]