Physical performance level in sarcomeric mitochondria creatine kinase knockout mouse model throughout ageing.

PURPOSE: The objective of the present study was to establish the role of sarcomeric mitochondrial creatine kinase (Mt-CK) in muscle energy output during exercise in a murine model of ageing (the Mt-CK knock-out mouse, Mt-CK-/-). METHODS: Three age groups of Mt-CK-/- mice and control male mice (6, 9, and 18 months of age) underwent incremental treadmill running tests. The maximum speed (Vpeak) and maximal oxygen consumption (VO2peak) values were recorded. Urine samples were analyzed using metabolomic techniques. The skeletal muscle (quadriceps) expression of proteins involved in mitochondria biogenesis, peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) and dynamin-related GTPase mitofusin 2 (Mnf2) were quantified. RESULTS: The VO2 peak (normalized to heart weight: HW) of 18-month-old (mo) Mt-CK-/- mice was 27% (p < 0.001) lower than in 18-mo control mice. The VO2peak/HW ratio was 29% (p < 0.001) lower in 18-mo Mt-CK-/- mice than in 6-mo (p < 0.001) and 32% (p < 0.001) than 9-mo Mt-CK-/- mice. With a 0° slope, Vpeak was 10% (p < 0.05) lower in 18-mo Mt-CK-/- mice than in 6-mo Mt-CK-/- mice but did not differ when comparing the 18-mo and 6-mo control groups. The skeletal muscles weight normalized on body weight in 6-mo Mt-CK-/- were 13 to 14% (p < 0.001, p < 0.05) lower versus the 6-mo control, in addition, the presence of branched-chain amino acids in the urine of 6-mo Mt-CK-/- mice suggests an imbalance in protein turnover (catabolism rather than anabolism) but we did not observe any age-related differences. The expression of PGC-1α and Mnf2 proteins in the quadriceps showed that age-related effects were more prominent than genotype effects. CONCLUSION: The present study showed ageing is potentialized by Mt-CK deficiency with regard to VO2peak, Vpeak and mitochondrial protein expression. Our results support that Mt-CK-/- mice undergo physiological adaptations, enabling them to survive and to perform as well as wild-type mice. Furthermore, it is possible that these adaptations in Mt-CK-/- mice have a high energy cost and might trigger premature ageing.

A new model of short acceleration-based training improves exercise performance in old mice.

In order to identify a more appealing exercise strategy for the elderly, we studied a mouse model to determine whether a less time-consuming training program would improve exercise performance, enzyme activities, mitochondrial respiration, and metabolomic parameters. We compared the effects of short-session (acceleration-based) training with those of long-session endurance training in 23-month-old mice. The short-session training consisted of five acceleration-based treadmill running sessions over 2 weeks (the acceleration group), whereas the endurance training consisted of five-one-hour treadmill sessions per week for 4 weeks (the endurance group). A control group of mice was also studied. In the acceleration group, the post-training maximum running speed and time to exhaustion were significantly improved, relative to pretraining values (+8% for speed, P<.05; +10% for time to exhaustion, P<.01). The post-training maximum running speed was higher in the acceleration group than in the endurance group (by 23%; P<.001) and in the control group (by 15%; P<.05). In skeletal muscle samples, the enzymatic activities of citrate synthase, lactate dehydrogenase, and creatine kinase were significantly higher in the acceleration group than in the endurance group. Furthermore, mitochondrial respiratory activity in the gastrocnemius was higher in the acceleration group than in the control group. A metabolomic urine analysis revealed a higher mean taurine concentration and a lower mean branched amino acid concentration in the acceleration group. In old mice, acceleration-based training appears to be an efficient way of increasing performance by improving both aerobic and anaerobic metabolism, and possibly by enhancing antioxidant defenses and maintaining muscle protein balance.

Transcriptional modulation of mitochondria biogenesis pathway at and above critical speed in mice.

High- or moderate-intensity endurance training leads to mitochondrial biogenesis via the peroxisome proliferator-activated receptor γ co-activator 1α (PGC-1α)/mitochondrial transcription factor A (Tfam) signaling pathway. Although this pathway is stimulated during acute exercise, the relationship between its activity and the intensity of the exercise has not been characterized. In animal studies, individualized running speeds have not previously been assessed. Here, we sought to determine whether this pathway was modulated after a bout of exhaustive exercise at different relative intensities (at and over critical speed (CS)). Our starting hypotheses were that (i) exercise-induced overexpression of PGC-1α in skeletal muscle falls at intensities above CS, and (ii) transcriptional activity of the mitochondrial biogenesis signaling cascade is intensity-sensitive at and above CS. To test these hypothesis, male Friend Virus B-Type mice were divided into a control group and three exercise groups (exercising at CS, peak velocity (vPeak) and 150 % CS, respectively). mRNA expression levels for genes involved in mitochondrial biogenesis signaling were analyzed in the quadriceps muscle. PGC-1α was overexpressed at all exercise intensities. We also identified that, PGC-1α mRNA expression was negatively correlated with exercise intensity and blood lactate levels but not with maximal oxygen uptake, vPeak, or CS. Expression of the PGC-1α co-activator peroxisome proliferator-activated receptor ß was negatively correlated with the exercise intensity. In contrast, expression levels of Tfam were dissociated from exercise intensity. Our data indicate that at the intensities used in endurance training, the expression of mitochondrial biogenesis genes is finely modulated by the relative intensity of exhaustive exercise.

Factors associated with perceived exertion and estimated time limit at lactate threshold.

The purpose was to identify the most predictive parameters for perceived exertion and estimated time limit responses at the velocity corresponding to the lactate concentration threshold. The former scale concerns the subject's current status (how hard he feels the exercise currently is) whereas the latter scale deals with a subjective prediction of how long the current exercise level can be maintained. Multiple regression equations were developed among physiological, psychological, nutritional, and individual parameters (subjects' characteristics and performances) as independent variables, and perceived exertion or estimated time limit as dependent variables. Independent variables were collected before or during an incremental running field test. 94 regional to national level athletes (47 endurance-trained runners, 11 sprinters, and 36 handball players) participated. Multiple stepwise regression showed that Rating of Perceived Exertion and Estimated Time Limit at the lactate threshold were mainly mediated by factors relative to the performance expressed in percentage of the maximal aerobic velocity. Secondary factors which contribute significantly as perceptual predictors were related to various classes of factors except for psychological factors.

Training content and potential impact on performance: a comparison of young male and female endurance-trained runners.

The purpose of the present investigation was to compare the content of 8 weeks of training in young endurance-trained male and female runners and study the potential impact of this training content on performance. Fourteen men and 11 women performed two criterion exercises until exhaustion on an outdoor track before and after the 8-week training period. The first test was a graded exercise to determine maximal aerobic velocity (Mav), the velocity at the lactate concentration threshold (v-Tlac), and the velocity at delta 50 (v delta50: the velocity halfway between Mav and v-Tlac). The second test was a constant run at v delta50 to determine the time to exhaustion at this velocity (tlimv delta50). Training logs were used to monitor the self-directed training sessions. The results showed that the women had a lower training volume but trained at higher exercise velocities than the men. However they presented similar values as the men for expected temporary performance capacity and did not improve their performance (Mav and tlimv delta50) over the 8-week period. After the training period, only v-Tlac (absolute and relative values) was slightly but significantly increased by training. These results could be due to the fact that both men and women did not train more than 10% of the total distance run at exercise velocities equal to or higher than their Mav and did not increase their training load during the 8-week training period. We suggest that changes in training content during the season, such as severe (long-duration or high-intensity) training sessions, may have improved their performance capacity.

Sex-related differences in ratings of perceived exertion and estimated time limit.

The purpose of the present investigation was i) to study the effect of sex on ratings of perceived exertion (RPE) and estimation of time limit (ETL) during runs to exhaustion at both absolute and relative physical and physiological reference criteria, ii) to propose some recommendations for exercise intensity prescription from both RPE and ETL according to sex. Eight male and eight female middle-distance endurance-trained runners performed two exercises until exhaustion on an outdoor track. The first test was a graded exercise to determine maximal aerobic velocity (vV.O2max), the velocity at the lactate threshold (vLT), and the velocity at delta 50 (vDelta50: the velocity halfway between vV.O2max and vLT). The second test was a constant all-out run at vDelta50 to determine the time to exhaustion at this intensity (tlim). The results of this study showed that the female runners perceived exercise as being harder, felt that they could endure less and had higher heart rate values than males for a given absolute velocity (km.h-1) whereas there were no difference between males and females for a given relative velocity (%vV.O2max). Moreover, the female runners perceived exercise as lighter and felt that they could endure more than the males for a given absolute time period (in s) whereas there was no difference between males and females for a given relative time period (%tlim). This result may be explained by the fact that the same exercise intensity or duration corresponded to higher %vV.O2max and lower %tlim for the females compared to the males. Consequently, physical trainers can prescribe the same perceived ratings for a given percentage of vV.O2max or tlim both in male and female athletes.

Influence of acetaminophen consumption on perceived exertion at the lactate concentration threshold.

The purpose of this investigation was to study effects of acetaminophen consumption on ratings of perceived exertion and estimated time limit responses at the lactate threshold. 98 young regional to national level athletes performed a graded exhausting exercise on an outdoor running track to estimate their maximal aerobic velocity and the velocity associated with their lactate concentration threshold. Urine (30 mL) was collected during this test and analysed for numerous substances. During urinary screening for doping substances, 9 acetaminophen consumers (9.2%) among the 98 included athletes were detected. These acetaminophen consumers have significantly lower perceived exertion at velocity corresponding to the lactate concentration threshold than nonconsumers (11.9 +/- 2.1 vs 13.6 +/- 2.1, respectively) although they were at the same relative exercise intensity. This result shows that acetaminophen consumption may have mediated the perceived exertion response at the lactate concentration threshold. This may then suggest that the pain induced by training load could be a factor in use of self-prescribed pain relievers. Such consumption must be taken into account by medical staff, trainers, or educators who have to give information on the use and adverse effects of this substance and to propose palliative methods to their athletes.

Use of acetaminophen in young subelite athletes.

AIM: The purpose of the present investigation was to look for other drugs besides doping substances in the urine of subelite athletes submitted to heavy training. METHODS: One hundred and forty-one young subelite athletes (in sprint, cycling, middle distance running and handball) were included in the study, with a control group of 89 high school pupils. Drugs were researched by high performance liquid chromatography using a diode array detector. RESULTS: Among the 212 subjects who agreed to give a urine sample, acetaminophen was detected: 9.5% for the subelite athletes versus 1.3% for the control group with a greater difference for sprint and cycling training (26.7% and 20%, respectively). Acetaminophen is used to treat both acute and chronic pains. It relieves pain by elevating the pain threshold. CONCLUSIONS: The use of acetaminophen has to be taken into account by medical staff, trainers and educators.

Influence of aerobic fitness level on measured and estimated perceived exertion during exhausting runs.

The purpose of the present investigation was 1) to study the effects of fitness level on perceived exertion (RPE) and estimated time limit (ETL) scales during exhausting runs, and 2) to predict time to exhaustion from RPE or ETL values collected during a constant run exercise. Eight high-fitness level and twelve moderate-fitness level endurance trained males performed two exhausting exercises on a 400-m running track. The first test was a graded exercise using a portable metabolic system to determine maximal oxygen uptake (V.O (2)max), the velocity associated with V.O (2)max (vV.O (2)max), the velocity at the lactate threshold (vLT) and the velocity at delta 50 (vDelta50 : the velocity halfway between vV.O (2)max and vLT). The second test was a constant run exercise at vDelta50 to determine the time to exhaustion at this intensity (tlimvDelta50). Moderate-fitness level athletes perceived exercise to be relatively more strenuous and felt that they could continue for less time than high-fitness level athletes at similar relative velocities. There was no effect of fitness level on perceived exertion for a given relative exercise duration. RPE corresponding to vLT was not statistically significantly different between the two levels groups. For the two groups, measured and predicted exhaustion time values, which were calculated from linear extrapolation of RPE and ETL values collected during the first 4 minutes of a submaximal constant run exercise, were not statistically significantly correlated. These results indicate that the aerobic fitness level seems to influence perceived exertion only during graded exercise. Consequently, if RPE is used to prescribe an exercise intensity, the prescription must be individualised regarding the aerobic fitness level of the athlete except for exercise intensities corresponding to vLT. Moreover, the perceived exertion pattern at the beginning of a submaximal constant run exercise could not be considered as a sensitive predictor of the point of self-imposed exhaustion whatever the fitness level of the athletes.

Influence of the type of training sport practised on psychological and physiological parameters during exhausting endurance exercises.

The present purpose was to study the influence of the type of training sport practised (long distance running, sprinting, handball) on ratings of perceived exertion (RPE), estimation of time limit (ETL), and heart rate (HR) on running tests. It was hypothesised that these parameters would be related to the type of training sport practised. 31 trained women (10 endurance-trained runners, 10 sprinters, and 11 handball players) performed two exercises to exhaustion on an outdoor track. The first test was a graded run to estimate maximal aerobic speed (SMA), i.e., the minimal speed which elicited maximal oxygen uptake. The second test was a constant all-out run at speed delta 50 (Sdelta50), which corresponded to the speed halfway between SMA and the speed at lactate threshold (SLT), to specify time to exhaustion at this intensity (TLIM). Sensations regarding RPE, ETL, and HR were recorded during these tests. SMA, Sdelta50, and SLT, expressed in absolute values (km x hr.(-1)) were statistically significantly different between groups (p < .05) whereas TLIM was not. The covariance analysis showed that endurance-trained runners perceived the exercise as lighter and presented lower HR than handball players and sprinters for a same running %SMA (p < .05). Moreover, endurance-trained runners felt that they could endure more than the other groups at a given %SMA or relative exhaustion time (%TLIM). These results mean that the type of training sport which has been performed may mediate perceptual responses and influence physiological parameters during exhausting exercises. These results are likely in part related to sport-specificity of the exercise mode used in tests. This point must be taken into consideration by physical trainers who have to prescribe exercise intensities during athletic seasons for different groups of athletes.

The effects of interval training on oxygen pulse and performance in supra-threshold runs.

The aim of this study was to examine (i) the effects of a severe interval training period on oxygen pulse kinetics (O2-p, the ratio between VO2 and heart rate), and (ii) to study the consequences of these effects on the variation of performance (time to exhaustion) during severe runs. Seven athletes were tested before and after an eight-weeks period of a specific intermittent training at v Delta 50, i.e., the intermediate velocity between the lactate threshold (vLT) and the velocity associated with VO2max (vVO2max ). During the test sessions, athletes performed an incremental test and an all-out test at the pretraining v Delta 50. After the training period they also completed an additional all-out test at the posttraining v Delta 50 (v Delta 50bis). Results showed that after training there was i) an increase in the O2-p maximal value during the incremental test (22.7 +/- 1.5 mlO2.b-1 vs. 20.6 +/- 1.5 mlO2.b-1; p < 0.04), ii) a decrease in the time to reach the O2-p steady state (TRO2-p ) at the same absolute v Delta 50 (33 +/- 7 s vs. 60 +/- 27 s; p < 0.04) and iii) an increase in the O2-p steady state duration (TSSO2-p) at the same absolute v Delta 50 (552 +/- 201 s vs. 407 +/- 106 s; p < 0.04). However, there was no relationship between the improvement of these two O 2 -p kinetics parameters (TRO2-p and TSS O2-p) and those of the performance. This study found that after an individualised interval-training program conducted at the same absolute velocity, the O2-p kinetics reached a steady state quicker and for a longer duration than before training. This is however not related with the improvement of performance.

Effect of training in humans on off- and on-transient oxygen uptake kinetics after severe exhausting intensity runs.

The purpose of this study was to examine the effect of 4 weeks of intense interval-training on the pulmonary off-transient oxygen uptake (V*O2) after running until exhaustion at the same absolute speed. Seven physical education students ran as follows in three maximal tests on a synthetic track (400 m) whilst breathing through a portable, telemetric metabolic analyser: firstly, in an incremental test which determined maximal oxygen uptake (V*O2max), the minimal speed associated with V*O2max (vV*O2max) and the speed at the lactate threshold ( v(LT)). Secondly, in two continuous severe intensity runs at 90% (R90) and 95% (R95) of vV*O2max. After training, the times to exhaustion ( t(lim)) at these two speeds (i.e. the time limits t(lim90) and t(lim95), respectively), were significantly increased at both speeds (+37% and +66% for t(lim90) and t(lim95), P=0.04 and 0.01, respectively) and v(LT) and vV*O2max were increased by 8% and 5%, respectively ( P<0.02). The time constants of the cardio-dynamic added to the metabolic phase (phases I+II) and of the slow phase (phase III) of oxygen kinetics in the on-transient phase decreased significantly after training ( P=0.05). However, the decrease in the time constants of oxygen kinetics in the on-transient phases II and III were not correlated with the improvement in performance (i.e. increase in t(lim)). After training the V*O2 off-transient phase was significantly faster [off-time constant (tau(off)) decreased significantly both after R90 and R95, P=0.03]. This decrease in tau(off) was correlated with the increase in t(lim90) ( r=0.795, P=0.03). The physiological factors best correlated with the increased performance after training were v(LT) for t(lim90) and vV*O2max for t(lim95).

Transplantation of autologous dorsal root ganglia into the peroneal nerve of adult rats: uni- and bidirectional axonal regrowth from the grafted DRG neurons.

Previous studies have demonstrated that transplanted dorsal root ganglion neurons (DRGNs) can survive and differentiate in a variety of orthotopic and heterotopic locations. In order to develop strategies aimed at restoring the sensory function following traumatic injury to the spinal cord and to its peripheral sensory connections, we have transplanted adult autologous dorsal root ganglia (DRGs) into the peroneal nerve of adult rats. Twelve female Sprague-Dawley rats were used. A segment of the peroneal nerve was isolated by double transection and ligature to prevent undesirable reinnervation. The left fifth cervical (C5) DRG was removed from its normal location and inserted into the midportion of the isolated nerve segment. One month after the grafting procedure, a morphological study included axonal retrograde labeling with True Blue (TB) and/or Diamidino Yellow (DY) applied on each cut end of the nerve segment, cell counting, and cell measurement after staining with cresyl violet. Compared to the C5 ganglion maintained in situ, the mean number of surviving DRGNs in the transplant was 1381, corresponding to a survival rate of 20%. Both singly (TB or DY) and doubly (TB + DY) stained DRGNs were encountered. The proportion of surviving neurons that appeared to be doubly labeled was 23%. These neurons were considered as having grown two opposite axonal projections, one into the "central" part of the nerve segment and a second one into its "peripheral" part. The present results give new insights and interesting prospects concerning the possibilities of reconstructing the sensory circuitry after central and/or peripheral injuries.

The role of cadence on the VO2 slow component in cycling and running in triathletes.

The purpose of this study was to compare the effect of two different types of cyclic severe exercise (running and cycling) on the VO2 slow component. Moreover we examined the influence of cadence of exercise (freely chosen [FF] vs. low frequency [LF]) on the hypothesis that: 1) a stride frequency lower than optimal and 2) a pedalling frequency lower than FF one could induce a larger and/or lower VO2 slow component. Eight triathletes ran and cycled to exhaustion at a work-rate corresponding to the lactate threshold + 50% of the difference between the work-rate associated with VO2max and the lactate threshold (delta 50) at a freely chosen (FF) and low frequency (LF: - 10 % of FF). The time to exhaustion was not significantly different for both types of exercises and both cadences (13 min 39 s, 15 min 43 s, 13 min 32 s, 15 min 05 s for running at FF and LF and cycling at FF and LF, respectively). The amplitude of the VO2 slow component (i.e. difference between VO2 at the last and the 3rd min of the exercise) was significantly smaller during running compared with cycling, but there was no effect of cadence. Consequently, there was no relationship between the magnitude of the VO2 slow component and the time to fatigue for a severe exercise (r = 0.20, p = 0.27). However, time to fatigue was inversely correlated with the blood lactate concentration for both modes of exercise and both cadences (r = - 0.42, p = 0.01). In summary, these data demonstrate that: 1) in subjects well trained for both cycling and running, the amplitude of the VO2 slow component at fatigue was larger in cycling and that it was not significantly influenced by cadence; 2) the VO2 slow component was not correlated with the time to fatigue. If the nature of the linkage between the VO2 slow component and the fatigue process remains unclear, the type of contraction regimen depending on exercise biomechanic characteristics seems to be determinant in the VO2 slow component phenomenon for a same level of training.

Estimation of the number and size of female adult rat C4, C5 and C6 dorsal root ganglia (DRG) neurons.

In previous studies primary sensory neurons of adult rats have been counted in lumbar dorsal root ganglia. However, different counting methods have given very different results and at the cervical level, recent data are scarce. In the present study, the number of neurons in C4, C5 and C6 adult rat ganglia was determined using two previously calibrated techniques. The stereological tool was preferred because it directly identifies neurons instead of nucleoli and is more efficient. The C4, C5 and C6 dorsal root ganglia were found to contain 7508+/-299, 6825+/-950 and 6858+/-923 neurons, respectively, and statistical analysis indicated that there was no significant difference between the three levels. There was, however, a great interindividual variation, which was also found at other levels of the spinal cord. The mean diameter of neurons in the C4, C5 and C6 dorsal root ganglia was determined and was 17.52, 20.16 and 20.68 microm, respectively. It is important to know more about the organization of the sensory systems in the normal rat. Once established, the number of neurons in these dorsal root ganglia could be compared with different pathological situations or experimental treatments such as developmental conditions, nerve section or ganglion transplantation.