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Mignardot J.-B.,University of Nantes | Mignardot J.-B.,Ecole Polytechnique Federale de Lausanne | Deschamps T.,University of Nantes | Barrey E.,CNRS Unit of Integrative Biology of Adaptation to Exercise | And 7 more authors.
Frontiers in Aging Neuroscience | Year: 2014

Falls are common in the elderly, and potentially result in injury and disability. Thus, preventing falls as soon as possible in older adults is a public health priority, yet there is no specific marker that is predictive of the first fall onset. We hypothesized that gait features should be the most relevant variables for predicting the first fall. Clinical baseline characteristics (e.g., gender, cognitive function) were assessed in 259 home-dwelling people aged 66 to 75 that had never fallen. Likewise, global kinetic behavior of gait was recorded from 22 variables in 1036 walking tests with an accelerometric gait analysis system. Afterward, monthly telephone monitoring reported the date of the first fall over 24 months. A principal components analysis was used to assess the relationship between gait variables and fall status in four groups: non-fallers, fallers from 0 to 6 months, fallers from 6 to 12 months and fallers from 12 to 24 months. The association of significant principal components (PC) with an increased risk of first fall was then evaluated using the area under the Receiver Operator Characteristic Curve (ROC). No effect of clinical confounding variables was shown as a function of groups. An eigenvalue decomposition of the correlation matrix identified a large statistical PC1 (termed "Global kinetics of gait pattern"), which accounted for 36.7% of total variance. Principal component loadings also revealed a PC2 (12.6% of total variance), related to the "Global gait regularity." Subsequent ANOVAs showed that only PC1 discriminated the fall status during the first 6 months, while PC2 discriminated the first fall onset between 6 and 12 months. After one year, any PC was associated with falls. These results were bolstered by the ROC analyses, showing good predictive models of the first fall during the first six months or from 6 to 12 months. Overall, these findings suggest that the performance of a standardized walking test at least once a year is essential for fall prevention. © 2014 Mignardot, Deschamps, Barrey, Auvinet, Berrut, Cornu, Constans and de Decker.

Barrey E.,CNRS Unit of Integrative Biology of Adaptation to Exercise | Barrey E.,CEA Grenoble | Saint-Auret G.,CEA Grenoble | Bonnamy B.,CNRS Unit of Integrative Biology of Adaptation to Exercise | And 3 more authors.
PLoS ONE | Year: 2011

Background: Because of the central functions of the mitochondria in providing metabolic energy and initiating apoptosis on one hand and the role that microRNA (miRNA) play in gene expression, we hypothesized that some miRNA could be present in the mitochondria for post-transcriptomic regulation by RNA interference. We intend to identify miRNA localized in the mitochondria isolated from human skeletal primary muscular cells. Methodology/Principal Findings: To investigate the potential origin of mitochondrial miRNA, we in-silico searched for microRNA candidates in the mtDNA. Twenty five human pre-miRNA and 33 miRNA aligments (E-value<0.1) were found in the reference mitochondrial sequence and some of the best candidates were chosen for a co-localization test. In situ hybridization of pre-mir-302a, pre-let-7b and mir-365, using specific labelled locked nucleic acids and confocal microscopy, demonstrated that these miRNA were localized in mitochondria of human myoblasts. Total RNA was extracted from enriched mitochondria isolated by an immunomagnetic method from a culture of human myotubes. The detection of 742 human miRNA (miRBase) were monitored by RT-qPCR at three increasing mtRNA inputs. Forty six miRNA were significantly expressed (2nd derivative method Cp>35) for the smallest RNA input concentration and 204 miRNA for the maximum RNA input concentration. In silico analysis predicted 80 putative miRNA target sites in the mitochondrial genome (E-value<0.05). Conclusions/Significance: The present study experimentally demonstrated for the first time the presence of pre-miRNA and miRNA in the human mitochondria isolated from skeletal muscular cells. A set of miRNA were significantly detected in mitochondria fraction. The origin of these pre-miRNA and miRNA should be further investigate to determine if they are imported from the cytosol and/or if they are partially processed in the mitochondria. © 2011 Barrey et al.

Mille-Hamard L.,CNRS Unit of Integrative Biology of Adaptation to Exercise | Billat V.L.,CNRS Unit of Integrative Biology of Adaptation to Exercise | Henry E.,CNRS Unit of Integrative Biology of Adaptation to Exercise | Bonnamy B.,CNRS Unit of Integrative Biology of Adaptation to Exercise | And 4 more authors.
BMC Medical Genomics | Year: 2012

Background: Erythropoietin (EPO) is known to improve exercise performance by increasing oxygen blood transport and thus inducing a higher maximum oxygen uptake (VO2max). Furthermore, treatment with (or overexpression of) EPO induces protective effects in several tissues, including the myocardium. However, it is not known whether EPO exerts this protective effect when present at physiological levels. Given that EPO receptors have been identified in skeletal muscle, we hypothesized that EPO may have a direct, protective effect on this tissue. Thus, the objectives of the present study were to confirm a decrease in exercise performance and highlight muscle transcriptome alterations in a murine EPO functional knock-out model (the EPO-d mouse). Methods. We determined VO2max peak velocity and critical speed in exhaustive runs in 17 mice (9 EPO-d animals and 8 inbred controls), using treadmill enclosed in a metabolic chamber. Mice were sacrificed 24h after a last exhaustive treadmill exercise at critical speed. The tibialis anterior and soleus muscles were removed and total RNA was extracted for microarray gene expression analysis. Results: The EPO-d mices hematocrit was about 50% lower than that of controls (p<0.05) and their performance level was about 25% lower (p<0.001). A total of 1583 genes exhibited significant changes in their expression levels. However, 68 genes were strongly up-regulated (normalized ratio>1.4) and 115 were strongly down-regulated (normalized ratio<0.80). The transcriptome data mining analysis showed that the exercise in the EPO-d mice induced muscle hypoxia, oxidative stress and proteolysis associated with energy pathway disruptions in glycolysis and mitochondrial oxidative phosphorylation. Conclusions: Our results showed that the lack of functional EPO induced a decrease in the aerobic exercise capacity. This decrease was correlated with the hematocrit and reflecting poor oxygen supply to the muscles. The observed alterations in the muscle transcriptome suggest that physiological concentrations of EPO exert both direct and indirect muscle-protecting effects during exercise. However, the signaling pathway involved in these protective effects remains to be described in detail. © 2012 Mille-Hamard et al.; licensee BioMed Central Ltd.

PubMed | University of Paris 13, CNRS Unit of Integrative Biology of Adaptation to Exercise, CNRS Structure and Activity of Normal and Pathological Biomolecules and University of Pittsburgh
Type: Journal Article | Journal: Metabolites | Year: 2016

Patients surviving sepsis demonstrate sustained inflammation, which has been associated with long-term complications. One of the main mechanisms behind sustained inflammation is a metabolic switch in parenchymal and immune cells, thus understanding metabolic alterations after sepsis may provide important insights to the pathophysiology of sepsis recovery. In this study, we explored metabolomics in a novel

PubMed | University of Paris 13, CNRS Structure and Activity of Normal and Pathological Biomolecules and CNRS Unit of Integrative Biology of Adaptation to Exercise
Type: | Journal: Scandinavian journal of medicine & science in sports | Year: 2016

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 2weeks (the acceleration group), whereas the endurance training consisted of five-one-hour treadmill sessions per week for 4weeks (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.

PubMed | Princess Nora Bint Abdulrahman University, University of Strasbourg, University of Brasilia, CNRS Unit of Integrative Biology of Adaptation to Exercise and 2 more.
Type: | Journal: Hypoxia (Auckland, N.Z.) | Year: 2016

Despite its well-known role in red blood cell production, it is now accepted that erythropoietin (Epo) has other physiological functions. Epo and its receptors are expressed in many tissues, such as the brain and heart. The presence of Epo/Epo receptors in these organs suggests other roles than those usually assigned to this protein. Thus, the aim of this review is to describe the effects of Epo deficiency on adaptation to normoxic and hypoxic environments and to suggest a key role of Epo on main physiological adaptive functions. Our original model of Epo-deficient (Epo-TAg

Triba M.N.,University of Paris 13 | Le Moyec L.,CNRS Unit of Integrative Biology of Adaptation to Exercise | Amathieu R.,University Paris Est Creteil | Goossens C.,University of Paris 13 | And 4 more authors.
Molecular BioSystems | Year: 2015

Among all the software packages available for discriminant analyses based on projection to latent structures (PLS-DA) or orthogonal projection to latent structures (OPLS-DA), SIMCA (Umetrics, Umeå Sweden) is the more widely used in the metabolomics field. SIMCA proposes many parameters or tests to assess the quality of the computed model (the number of significant components, R2, Q2, pCV-ANOVA, and the permutation test). Significance thresholds for these parameters are strongly application-dependent. Concerning the Q2 parameter, a significance threshold of 0.5 is generally admitted. However, during the last few years, many PLS-DA/OPLS-DA models built using SIMCA have been published with Q2 values lower than 0.5. The purpose of this opinion note is to point out that, in some circumstances frequently encountered in metabolomics, the values of these parameters strongly depend on the individuals that constitute the validation subsets. As a result of the way in which the software selects members of the calibration and validation subsets, a simple permutation of dataset rows can, in several cases, lead to contradictory conclusions about the significance of the models when a K-fold cross-validation is used. We believe that, when Q2 values lower than 0.5 are obtained, SIMCA users should at least verify that the quality parameters are stable towards permutation of the rows in their dataset. This journal is © The Royal Society of Chemistry.

Van de Louw A.,CNRS Unit of Integrative Biology of Adaptation to Exercise | Van de Louw A.,Center Hospitalier Sud Francilien | Medigue C.,Institute National Of Recherche En Informatique Et En Automatique | Papelier Y.,EA 3544 | Cottin F.,CNRS Unit of Integrative Biology of Adaptation to Exercise
Respiratory Research | Year: 2010

Background: Baroreflex allows to reduce sudden rises or falls of arterial pressure through parallel RR interval fluctuations induced by autonomic nervous system. During spontaneous breathing, the application of positive end-expiratory pressure (PEEP) may affect the autonomic nervous system, as suggested by changes in baroreflex efficiency and RR variability. During mechanical ventilation, some patients have stable cardiorespiratory phase difference and high-frequency amplitude of RR variability (HF-RR amplitude) over time and others do not. Our first hypothesis was that a steady pattern could be associated with reduced baroreflex sensitivity and HF-RR amplitude, reflecting a blunted autonomic nervous function. Our second hypothesis was that PEEP, widely used in critical care patients, could affect their autonomic function, promoting both steady pattern and reduced baroreflex sensitivity.Methods: We tested the effect of increasing PEEP from 5 to 10 cm H2O on the breathing variability of arterial pressure and RR intervals, and on the baroreflex. Invasive arterial pressure, ECG and ventilatory flow were recorded in 23 mechanically ventilated patients during 15 minutes for both PEEP levels. HF amplitude of RR and systolic blood pressure (SBP) time series and HF phase differences between RR, SBP and ventilatory signals were continuously computed by complex demodulation. Cross-spectral analysis was used to assess the coherence and gain functions between RR and SBP, yielding baroreflex-sensitivity indices.Results: At PEEP 10, the 12 patients with a stable pattern had lower baroreflex gain and HF-RR amplitude of variability than the 11 other patients. Increasing PEEP was generally associated with a decreased baroreflex gain and a greater stability of HF-RR amplitude and cardiorespiratory phase difference. Four patients who exhibited a variable pattern at PEEP 5 became stable at PEEP 10. At PEEP 10, a stable pattern was associated with higher organ failure score and catecholamine dosage.Conclusions: During mechanical ventilation, stable HF-RR amplitude and cardiorespiratory phase difference over time reflect a blunted autonomic nervous function which might worsen as PEEP increases. © 2010 Van de Louw et al; licensee BioMed Central Ltd.

Martin V.,CNRS Unit of Integrative Biology of Adaptation to Exercise | Nicol C.,Aix - Marseille University
Movement and Sports Sciences - Science et Motricite | Year: 2010

Eccentric- and stretch-shortening cycle (SSC) type exercises are of great functional interest for human locomotion. However, the repetition of such types of muscle actions during prolonged exercises or at high intensities may induce acute and delayed structuro-functional deficits, frequently associated with delayed onset muscle soreness (DOMS). These alterations are reversible owing to the intervention of an inflammatory process. The associated biochemical, thermal and mechanical changes are suggested to sensitize small diameter muscles afferents (type III and IV) that may then contribute to the DOMS generation and neural adjustments to the contractile failure. © ACAPS, EDP Sciences, 2010.

PubMed | CNRS Unit of Integrative Biology of Adaptation to Exercise
Type: | Journal: Frontiers in physiology | Year: 2016

In the field of comparative physiology, it remains to be established whether the concept of VO2max is valid in the mouse and, if so, how this value can be accurately determined. In humans, VO2max is generally considered to correspond to the plateau observed when VO2 no longer rises with an increase in workload. In contrast, the concept of VO2peak tends to be used in murine studies. The objectives of the present study were to determine whether (i) a continuous ramp protocol yielded a higher VO2peak than a stepwise, incremental protocol, and (ii) the VO2peak measured in the ramp protocol corresponded to VO2max. The three protocols (based on intensity-controlled treadmill running until exhaustion with eight female FVB/N mice) were performed in random order: (a) an incremental protocol that begins at 10 m.min(-1) speed and increases by 3 m.min(-1) every 3 min. (b) a ramp protocol with slow acceleration (3 m.min(-2)), and (c) a ramp protocol with fast acceleration (12 m.min(-2)). Each protocol was performed with two slopes (0 and 25). Hence, each mouse performed six exercise tests. We found that the value of VO2peak was protocol-dependent (p < 0.05) and was highest (59.0 ml.kg (0.75).min(-1)) for the 3 m.min(-2) 0 ramp protocol. In the latter, the presence of a VO2max plateau was associated with the fulfillment of two secondary criteria (a blood lactate concentration >8 mmol.l(-1) and a respiratory exchange ratio >1). The total duration of the 3 m.min(-2) 0 ramp protocol was shorter than that of the incremental protocol. Taken as a whole, our results suggest that VO2max in the mouse is best determined by applying a ramp exercise protocol with slow acceleration and no treadmill slope.

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