Oxidative capacity and ageing in human muscle. Combined training enhances skeletal muscle mitochondrial oxidative capacity independent of age. Large energetic adaptations of elderly muscle to resistance and endurance training. Skeletal muscle mitochondrial function and lean body mass in healthy exercising elderly Endurance Exercise as a Countermeasure for Aging Effects of endurance training on oxidative capacity and structural composition of human arm and leg muscles. Mitochondrial Capacity in Skeletal Muscle Is Not Stimulated by Weight Loss Despite Increases in Insulin Action and Decreases in Intramyocellular Lipid Content Effects of endurance training on mitochondrial ultrastructure and fiber type distribution in skeletal muscle of patients with stable chronic heart failure. Functional impact of high protein intake on healthy elderly people. Lifelong physical activity prevents an age-related reduction in arterial and skeletal muscle nitric oxide bioavailability in humans. Calorie Restriction Increases Muscle Mitochondrial Biogenesis in Healthy Humans Low- and high-volume strength training induces similar neuromuscular improvements in muscle quality in elderly women The Effect of Neoadjuvant Chemoradiotherapy on Whole-Body Physical Fitness and Skeletal Muscle Mitochondrial Oxidative Phosphorylation In Vivo in Locally Advanced Rectal Cancer Patients – An Observational Pilot Study Quercetin's influence on exercise performance and muscle mitochondrial biogenesis. Effect of interval versus continuous training on cardiorespiratory and mitochondrial functions: relationship to aerobic performance improvements in sedentary subjects. Effects of intermittent hypoxic training on amino and fatty acid oxidative combustion in human permeabilized muscle fibers. The effects of training in hyperoxia vs. normoxia on skeletal muscle enzyme activities and exercise performance.
This study determined the decline in oxidative capacity per volume of human vastus lateralis muscle between nine adult ( mean age 38.8 years ) and 40 elderly ( mean age 68.8 years ) human subjects ( age range 25 - 80 years ) . We based our oxidative capacity estimates on the kinetics of changes in creatine phosphate content ( [ PCr ] ) during recovery from exercise as measured by (31)P magnetic resonance ( MR ) spectroscopy . A matched muscle biopsy sample permitted determination of mitochondrial volume density and the contribution of the loss of mitochondrial content to the decline in oxidative capacity with age . The maximal oxidative phosphorylation rate or oxidative capacity was estimated from the PCr recovery rate constant ( k(PCr ) ) and the [ PCr ] in accordance with a simple electrical circuit model of mitochondrial respiratory control . Oxidative capacity was 50 % lower in the elderly vs. the adult group ( 0.61 + /- 0.04 vs. 1.16 + /- 0.147 mM ATP s(-1 ) ) . Mitochondrial volume density was significantly lower in elderly compared with adult muscle ( 2.9 + /- 0.15 vs. 3.6 + /- 0.11 % ) . In addition , the oxidative capacity per mitochondrial volume ( 0.22 + /- 0.042 vs. 0.32 + /- 0.015 mM ATP ( s % ) ( -1 ) ) was reduced in elderly vs. adult subjects . This study showed that elderly subjects had nearly 50 % lower oxidative capacity per volume of muscle than adult subjects . The cellular basis of this drop was a reduction in mitochondrial content , as well as a lower oxidative capacity of the mitochondria with age CONTEXT Skeletal muscle from sedentary older adults exhibits reduced mitochondrial abundance and oxidative capacity . OBJECTIVE The primary objective was to determine whether 8 weeks of combined training ( CT ) has a more robust effect than endurance training ( ET ) or resistance training ( RT ) on mitochondrial physiology in healthy young ( 18 - 30 years ) and older ( ≥ 65 years ) adults . INTERVENTION Thirty-four young and 31 older adults were r and omly assigned to 8 weeks of ET , RT , and control/CT .  Control subjects completed 8 weeks of no exercise ( control ) followed by 8 weeks of CT  . Body composition , skeletal muscle strength , and peak oxygen uptake were measured before and after the intervention . Vastus lateralis muscle biopsy sample s were obtained before and 48 hours after the intervention . Mitochondrial physiology was evaluated by high-resolution respirometry and expression of mitochondrial proteins and transcription factors by quantitative PCR and immunoblotting . RESULTS ET and CT significantly increased oxidative capacity and expression of mitochondrial proteins and transcription factors . All training modalities improved body composition , cardiorespiratory fitness , and skeletal muscle strength . CT induced the most robust improvements in mitochondria-related outcomes and physical characteristics despite lower training volumes for the ET and RT components . Importantly , most of the adaptations to training occurred independent of age . CONCLUSION Collectively , these results demonstrate that both ET and CT increase muscle mitochondrial abundance and capacity although CT induced the most robust improvements in the outcomes measured . In conclusion , CT provides a robust exercise regimen to improve muscle mitochondrial outcomes and physical characteristics independent of age This study determined the cellular energetic and structural adaptations of elderly muscle to exercise training .  Forty male and female subjects ( 69.2 + /- 0.6 yr ) were assigned to a control group or 6 mo of endurance ( ET ) or resistance training ( RT ) . We used magnetic resonance spectroscopy and imaging to characterize energetic properties and size of the quadriceps femoris muscle . The phosphocreatine and pH changes during exercise yielded the muscle oxidative properties , glycolytic ATP synthesis , and contractile ATP dem and . Muscle biopsies taken from the same site as the magnetic resonance measurements were used to determine myosin heavy chain isoforms , metabolite concentrations , and mitochondrial volume densities . The ET group showed changes in all energetic pathways : oxidative capacity ( + 31 % ) , contractile ATP dem and ( -21 % ) , and glycolytic ATP supply ( -56 % ) . The RT group had a large increase in oxidative capacity ( 57 % ) . Only the RT group exhibited change in structural properties : a rise in mitochondrial volume density ( 31 % ) and muscle size ( 10 % ) . These results demonstrate large energetic , but smaller structural , adaptations by elderly muscle with exercise training . The rise in oxidative properties with both ET and RT suggests that the aerobic pathway is particularly sensitive to exercise training in elderly muscle . Thus elderly muscle remains adaptable to chronic exercise , with large energetic changes accompanying both ET and RT BACKGROUND The decline in muscle mass ( sarcopenia ) with aging may be related to a decline in mitochondrial function . However , investigators have yet to reach a consensus as to whether a decline in mitochondrial function can be attenuated by physical activity has yet to reach a consensus . METHODS Using dynamic 31PMRS to measure mitochondrial function , we measured baseline Phosphocreatine ( PCr ) , inorganic phosphate ( Pi ) , phosphodiester ( PDE ) , [ ADP ] , pH and recovery times ( t(1/2 ) ) for PCr and [ ADP ] following exercise , in 45 older ( 73+/-4 years , SD ) , and 20 younger subjects ( 25+/-4 years , SD ) who were matched for body mass across high and low activity levels and within age and sex groupings . RESULTS Baseline PCr , and Pi , were lower , and PDE higher in the older subjects compared to younger subjects ( all P<0.01 ) . The t(1/2)(ADP ) was longer in older subjects ( P<0.001 ) controlling for age and sex in the low activity group ( P=0.02 ) . In the older low activity groups , t(1/2)(PCr ) was longer than high activity groups . Higher PDE levels were positively correlated with longer t(1/2)(PCr ) in the older low activity females ( both P<0.05 ) . CONCLUSIONS Our data suggests that mitochondrial function declines with age in healthy , exercising elderly adults and that the decline appears to be influenced by the level of physical activity OBJECTIVE — We determined whether reduced insulin sensitivity , mitochondrial dysfunction , and other age-related dysfunctions are inevitable consequences of aging or secondary to physical inactivity . RESEARCH DESIGN AND METHODS — Insulin sensitivity was measured by hyperinsulinemic-euglycemic clamp and ATP production in mitochondria isolated from vastus lateralis biopsies of 42 healthy sedentary and endurance-trained young ( 18–30 years old ) and older ( 59–76 years old ) subjects . Expression of proteins involved in fuel metabolism was measured by mass spectrometry .  Citrate synthase activity , mitochondrial DNA ( mtDNA ) abundance , and expression of nuclear-encoded transcription factors for mitochondrial biogenesis were measured . SIRT3 , a mitochondrial sirtuin linked to lifespan-enhancing effects of caloric restriction , was measured by immunoblot . RESULTS — Insulin-induced glucose disposal and suppression of endogenous glucose production were higher in the trained young and older subjects , but no age effect was noted . Age-related decline in mitochondrial oxidative capacity was absent in endurance-trained individuals . Although endurance-trained individuals exhibited higher expression of mitochondrial proteins , mtDNA , and mitochondrial transcription factors , there were persisting effects of age . SIRT3 expression was lower with age in sedentary but equally elevated regardless of age in endurance-trained individuals . CONCLUSIONS — The results demonstrate that reduced insulin sensitivity is likely related to changes in adiposity and to physical inactivity rather than being an inevitable consequence of aging . The results also show that regular endurance exercise partly normalizes age-related mitochondrial dysfunction , although there are persisting effects of age on mtDNA abundance and expression of nuclear transcription factors and mitochondrial protein . Furthermore , exercise may promote longevity through pathways common to effects of caloric restriction Six healthy subjects performed endurance training of the same duration with legs and arms consecutively .  Performance and muscle structure were measured before and after training in lower and upper limbs . Training induced similar increases in maximal oxygen consumption ( 6 + /- 1 vs. 7 + /- 2 mL min-1 kg-1 : legs vs. arms , P > 0.05 ) and mitochondrial volume in leg and arm muscles ( 42 + /- 12 vs. 31 + /- 11 % : legs vs. arms , P > 0.05 ) . The gain in mitochondrial volume after training was achieved solely by increasing the fraction of mitochondria ( + 40 + /- 11 % , P < 0.05 ) in the same muscle volume ( + 2 + /- 2 % , P > 0.05 ) in the legs . In contrast , increased muscle volume ( + 14 + /- 3 % , P < 0.05 ) , in addition to a tendency for an increase in mitochondrial fraction ( + 16 + /- 11 % , P > 0.05 ) , occurred in the arms after training . Thus , similar improvements in muscle oxidative capacity in upper and lower limbs were brought about by different mechanisms . It is suggested that due to infrequent use and a lack of load-bearing function , arm muscle volume is underdeveloped in untrained , sedentary or detrained/injured subjects and that the mode of endurance training used in this study is sufficient to enlarge arm muscle volume as well as aerobic capacity OBJECTIVE — In obesity and type 2 diabetes , exercise combined with weight loss increases skeletal muscle mitochondrial capacity . It remains unclear whether mitochondrial capacity increases because of weight loss , improvements in insulin resistance , or physical training . In this study , we examined the effects of an intervention of weight loss induced by diet and compared these with those of a similar intervention of weight loss by diet with exercise . Both are known to improve insulin resistance , and we tested the hypothesis that physical activity , rather than improved insulin resistance , is required to increase mitochondrial capacity of muscle . RESEARCH DESIGN AND METHODS — Sixteen sedentary overweight/obese volunteers were r and omized to a 16-week intervention of diet ( n = 7 ) or diet plus exercise ( n = 9 ) . Insulin sensitivity was measured using euglycemic clamps . Mitochondria were examined in muscle biopsies before and after intervention . We measured mitochondrial content and size by electron microscopy , electron transport chain ( ETC ) activity , cardiolipin content , and mitochondrial DNA content . Intramyocellular content of lipid ( IMCL ) and fiber-type distribution were determined by histology . RESULTS — The diet-only and diet plus exercise groups achieved similar weight loss ( 10.8 and 9.2 % , respectively ) ; only the diet plus exercise group improved aerobic capacity . Insulin sensitivity improved similarly in both groups . Mitochondrial content and ETC activity increased following the diet plus exercise intervention but remained unchanged following the diet-only intervention , and mitochondrial size decreased with weight loss despite improvement in insulin resistance . IMCL decreased in the diet-only but not in the diet plus exercise intervention . CONCLUSIONS — Despite similar effects to improve insulin resistance , these interventions had differential effects on mitochondria . Clinical ly significant weight loss in the absence of increased physical activity ameliorates insulin resistance and IMCL but does not increase muscle mitochondrial capacity in obesity OBJECTIVES The present study was design ed to evaluate the effects of an ambulatory training program in patients with chronic heart failure ( CHF ) on the ultrastructural morphology of mitochondria and fiber type distribution of skeletal muscle and its relation to peripheral perfusion . BACKGROUND Recent studies in patients with CHF have suggested that intrinsic abnormalities in skeletal muscle can contribute to the development of early lactic acidosis and fatigue during exercise . METHODS ; Patients were prospect ively r and omized to either a training group ( n = 9 ; mean [ + /- SD ] left ventricular ejection fraction [ LVEF ] 26 + /- 10 ) participating in an ambulatory training program or to a physically inactive control group ( n = 9 ; LVEF 28 + /- 10 % ) . At baseline and after 6 months , patients underwent symptom-limited bicycle exercise testing with measurement of central and peripheral hemodynamic variables as well as percutaneous needle biopsies of the vastus lateralis muscle . The mitochondrial ultrastructure of skeletal muscle was analyzed by ultrastructural morphometry ; cytochrome c oxidase activity was visualized by histochemistry and subsequently quantitated by morphometry . The fiber type distribution was determined by adenosine triphosphatase staining . RESULTS After 6 months of exercise training there was a significant increase of 41 % in the surface density of cytochrome c oxidase-positive mitochondria ( SVMOcox+ ) ( p < 0.05 vs. control ) and of 43 % in the surface density of mitochondrial cristae ( SVMC ) ( p < 0.05 vs. control ) . Furthermore , exercise training induced a 92 % increase in the surface density of the mitochondrial inner border membrane ( p < 0.05 vs. control ) . In contrast , the total number of cytochrome c oxidase-positive mitochondria remained essentially unchanged . Exercise-induced improvement in peak oxygen uptake was closely linked to changes in SVMOcox+ ( p < 0.01 , r = 0.66 ) . After exercise training , changes in submaximal femoral venous lactate levels were not related to changes in submaximal leg blood flow ( r = -0.4 ) , but were inversely related to changes in the volume density of mitochondria ( p = 0.01 ; r = -0.6 ) as well as to changes in SVMC ( p < 0.05 ; r = -0.5 ) . After exercise training there was a " reshift " from type II to type I fibers ( p < 0.05 vs. control ) . CONCLUSIONS Patients with CHF who engage in regular physical exercise show enhanced oxidative enzyme activity in the working skeletal muscle and a concomitant reshift to type I fibers . These exercise-induced changes in oxidative capacity appear to be unrelated to changes in peripheral perfusion Decline in muscle mass , protein synthesis , and mitochondrial function occurs with age , and amino acids are reported to enhance both muscle protein synthesis and mitochondrial function . It is unclear whether increasing dietary protein intake corrects postabsorptive muscle changes in aging . We determined whether a 10-day diet of high [ HP ; 3.0 g protein x kg fat-free mass (FFM)(-1 ) x day(-1 ) ] vs. usual protein intake ( UP ; 1.5 g protein x kg FFM(-1 ) x day(-1 ) ) favorably affects mitochondrial function , protein metabolism , and nitrogen balance or adversely affects insulin sensitivity and glomerular filtration rate ( GFR ) in 10 healthy younger ( 24+/-1 yr ) and 9 older ( 70+/-2 yr ) participants in a r and omized crossover study .  Net daily nitrogen balance increased equally in young and older participants , but postabsorptive catabolic state also increased , as indicated by higher whole body protein turnover and leucine oxidation with no change in protein synthesis . Maximal muscle mitochondrial ATP production rate was lower in older people , with no change occurring in diet . GFR was lower in older people , and response to HP was significantly different between the two groups , with a significant increase occurring only in younger people , thus widening the differences in GFR between the young and older participants . In conclusion , a short-term high-protein diet increased net daily nitrogen balance but increased the postabsorptive use of protein as a fuel . HP did not enhance protein synthesis or muscle mitochondrial function in either young or older participants . Additionally , widening differences in GFR between young and older patients is a potential cause of concern in using HP diet in older people Ageing has been proposed to be associated with increased levels of reactive oxygen species ( ROS ) that scavenge nitric oxide ( NO ) . In eight young sedentary ( 23 ± 1 years ; Y ) , eight older lifelong sedentary ( 66 ± 2 years ; OS ) and eight older lifelong physically active subjects ( 62 ± 2 years ; OA ) , we studied the effect of ROS on systemic and skeletal muscle NO bioavailability and leg blood flow by infusion of the antioxidant N-acetylcysteine ( NAC ) . Infusion of NAC  increased the bioavailability of NO in OS , as evidence d by an increased concentration of stable metabolites of NO ( NOx ) in the arterial and venous circulation and in the muscle interstitium . In OA , infusion of NAC only increased NOx concentrations in venous plasma whereas in Y , infusion of NAC did not affect NOx concentrations . Skeletal muscle protein levels of endothelial and neuronal NO synthase were 32 % and 24 % higher , respectively , in OA than in OS . Exercise at 12 W elicited a lower leg blood flow response that was associated with a lower leg oxygen uptake in OS than in Y. The improved bioavailability of NO in OS did not increase blood flow during exercise . These data demonstrate that NO bioavailability is compromised in the systemic circulation and in the musculature of sedentary ageing humans due to increased oxidative stress . Lifelong physical activity opposes this effect within the trained musculature and in the arterial circulation . The lower blood flow response to leg exercise in ageing humans is not associated with a reduced NO bioavailability Background Caloric restriction without malnutrition extends life span in a range of organisms including insects and mammals and lowers free radical production by the mitochondria . However , the mechanism responsible for this adaptation are poorly understood . Methods and Findings The current study was undertaken to examine muscle mitochondrial bioenergetics in response to caloric restriction alone or in combination with exercise in 36 young ( 36.8 ± 1.0 y ) , overweight ( body mass index , 27.8 ± 0.7 kg/m2 ) individuals r and omized into one of three groups for a 6-mo intervention : Control , 100 % of energy requirements ; CR , 25 % caloric restriction ; and CREX , caloric restriction with exercise ( CREX ) , 12.5 % CR + 12.5 % increased energy expenditure ( EE ) . In the controls , 24-h EE was unchanged , but in CR and CREX it was significantly reduced from baseline even after adjustment for the loss of metabolic mass ( CR , −135 ± 42 kcal/d , p = 0.002 and CREX , −117 ± 52 kcal/d , p = 0.008 ) . Participants in the CR and CREX groups had increased expression of genes encoding proteins involved in mitochondrial function such as PPARGC1A , TFAM , eNOS , SIRT1 , and PARL ( all , p < 0.05 ) . In parallel , mitochondrial DNA content increased by 35 % ± 5 % in the CR group ( p = 0.005 ) and 21 % ± 4 % in the CREX group ( p < 0.004 ) , with no change in the control group ( 2 % ± 2 % ) . However , the activity of key mitochondrial enzymes of the TCA ( tricarboxylic acid ) cycle ( citrate synthase ) , beta-oxidation ( beta-hydroxyacyl-CoA dehydrogenase ) , and electron transport chain ( cytochrome C oxidase II ) was unchanged . DNA damage was reduced from baseline in the CR ( −0.56 ± 0.11 arbitrary units , p = 0.003 ) and CREX ( −0.45 ± 0.12 arbitrary units , p = 0.011 ) , but not in the controls . In primary cultures of human myotubes , a nitric oxide donor ( mimicking eNOS signaling ) induced mitochondrial biogenesis but failed to induce SIRT1 protein expression , suggesting that additional factors may regulate SIRT1 content during CR . Conclusions The observed increase in muscle mitochondrial DNA in association with a decrease in whole body oxygen consumption and DNA damage suggests that caloric restriction improves mitochondrial function in young non-obese adults The aim of this study was to compare the effects of low- and high-volume strength training on strength , muscle activation and muscle thickness ( MT ) of the lower- and upper-body , and on muscle quality ( MQ ) of the lower-body in older women . Twenty apparently healthy elderly women were r and omly assigned into two groups : low-volume ( LV , n=11 ) and high-volume ( HV , n=9 ) . The LV group performed one-set of each exercise , while the HV group performed three-sets of each exercise , twice weekly for 13 weeks . MQ was measured by echo intensity obtained by ultrasonography ( MQEI ) , strength per unit of muscle mass ( MQST ) , and strength per unit of muscle mass adjusted with an allometric scale ( MQAS ) . Following training , there was a significant increase ( p≤0.001 ) in knee extension 1-RM ( 31.8±20.5 % for LV and 38.3±7.3 % for HV ) and in elbow flexion 1-RM ( 25.1±9.5 % for LV and 26.6±8.9 % for HV ) and in isometric maximal strength of the lower-body ( p≤0.05 ) and upper-body ( p≤0.001 ) , with no difference between groups . The maximal electromyographic activation for both groups increased significantly ( p≤0.05 ) in the vastus medialis and biceps brachii , with no difference between groups . All MT measurements of the lower- and upper-body increased similarly in both groups ( p≤0.001 ) . Similar improvements were also observed in MQEI ( p≤0.01 ) , MQST , and MQAS ( p≤0.001 ) for both groups . These results demonstrate that low- and high-volume strength training promote similar increases in neuromuscular adaptations of the lower- and upper-body , and in MQ of the lower-body in elderly women Background In the United Kingdom , patients with locally advanced rectal cancer routinely receive neoadjuvant chemoradiotherapy . However , the effects of this on physical fitness are unclear . This pilot study is aim ed to investigate the effect of neoadjuvant chemoradiotherapy on objective ly measured in vivo muscle mitochondrial function and whole-body physical fitness . Methods We prospect ively studied 12 patients with rectal cancer who completed st and ardized neoadjuvant chemoradiotherapy , recruited from a large tertiary cancer centre , between October 2012 and July 2013 . All patients underwent a cardiopulmonary exercise test and a phosphorus magnetic resonance spectroscopy quadriceps muscle exercise-recovery study before and after neoadjuvant chemoradiotherapy . Data were analysed and reported blind to patient identity and clinical course . Primary variables of interest were the two physical fitness measures ; oxygen uptake at estimated anaerobic threshold and oxygen uptake at Peak exercise ( ml.kg−1.min−1 ) , and the post-exercise phosphocreatine recovery rate constant ( min−1 ) , a measure of muscle mitochondrial capacity in vivo .  Results Median age was 67 years ( IQR 64–75 ) . Differences ( 95%CI ) in all three primary variables were significantly negative post-NACRT : Oxygen uptake at estimated anaerobic threshold −2.4 ml.kg−1.min−1 ( −3.8 , −0.9 ) , p = 0.004 ; Oxygen uptake at Peak −4.0 ml.kg−1.min−1 ( −6.8 , −1.1 ) , p = 0.011 ; and post-exercise phosphocreatine recovery rate constant −0.34 min−1 ( −0.51 , −0.17 ) , p<0.001 . Conclusion The significant decrease in both whole-body physical fitness and in vivo muscle mitochondrial function raises the possibility that muscle mitochondrial mechanisms , no doubt multifactorial , may be important in deterioration of physical fitness following neoadjuvant chemoradiotherapy . This may have implication s for targeted interventions to improve physical fitness pre-surgery . Trial Registration Clinical trials.gov registration PURPOSE To determine the influence of 2 wk of quercetin ( Q ; 1000 mg x d(-1 ) ) compared with placebo ( P ) supplementation on exercise performance and skeletal muscle mitochondrial biogenesis in untrained , young adult males ( N = 26 , age = 20.2 + /- 0.4 yr , VO2max = 46.3 + /- 1.2 mL x kg(-1 ) x min(-1 ) ) . METHODS Using a r and omized , crossover design with a 2-wk washout period , subjects provided blood and muscle biopsy sample s presupplementation and postsupplementation periods and were given 12-min time trials on 15 % grade d treadmills after 60 min of moderate exercise preloads at 60 % VO2max . RESULTS Plasma Q levels rose significantly in Q versus P during the 2-wk supplementation period ( interaction P value < 0.001 ) . During the 12-min trial , the net change in distance achieved was significantly greater during Q ( 2.9 % ) compared with P ( -1.2 % ; 29.5 + /- 11.5 vs -11.9 + /- 16.0 m , respectively , P = 0.038 ) . Skeletal muscle messenger RNA expression tended to increase ( range = 16 - 25 % ) during Q versus P for sirtuin 1 ( interaction effect , P = 0.152 ) , peroxisome proliferator-activated receptor gamma coactivator-1alpha ( P = 0.192 ) , cytochrome c oxidase ( P = 0.081 ) , and citrate synthase ( P = 0.166 ) . Muscle mitochondrial DNA ( relative copy number per diploid nuclear genome ) increased 140 + /- 154 ( 4.1 % ) with Q compared with -225 + /- 157 ( 6.0 % decrease ) with P ( P = 0.098 ) . CONCLUSIONS In summary , 1000 mg x d(-1 ) Q versus P for 2 wk by untrained males was associated with a small but significant improvement in 12-min treadmill time trial performance and modest but insignificant increases in the relative copy number of mitochondrial DNA and messenger RNA levels of four genes related to mitochondrial biogenesis The goal of the study was to determine the effects of continuous ( CT ) vs. intermittent ( IT ) training yielding identical mechanical work and training duration on skeletal muscle and cardiorespiratory adaptations in sedentary subjects . Eleven subjects ( 6 men and 5 women , 45 + /- 3 years ) were r and omly assigned to either of the two 8-wk training programs in a cross-over design , separated by 12 wk of detraining .  Maximal oxygen uptake ( Vo2max ) increased after both trainings ( 9 % with CT vs. 15 % with IT ) , whereas only IT was associated with faster Vo2 kinetics ( tau : 68.0 + /- 1.6 vs. 54.9 + /- 0.7 s , P < 0.05 ) measured during a test to exhaustion ( TTE ) and with improvements in maximal cardiac output ( Qmax , from 18.1 + /- 1.1 to 20.1 + /- 1.2 l/min ; P < 0.01 ) . Skeletal muscle mitochondrial oxidative capacities ( Vmax ) were only increased after IT ( 3.3 + /- 0.4 before and 4.5 + /- 0.6 micromol O2 x min(-1 ) x g dw(-1 ) after training ; P < 0.05 ) , whereas capillary density increased after both trainings , with a two-fold higher enhancement after CT ( + 21 + /- 1 % for IT and + 40 + /- 3 % after CT , P < 0.05 ) . The gain of Vmax was correlated with the gain of TTE and the gain of Vo2max with IT . The gain of Qmax was also correlated with the gain of VO2max . These results suggest that fluctuations of workload and oxygen uptake during training sessions , rather than exercise duration or global energy expenditure , are key factors in improving muscle oxidative capacities . In an integrative view , IT seems optimal in maximizing both peripheral muscle and central cardiorespiratory adaptations , permitting significant functional improvement . These data support the symmorphosis concept in sedentary subjects The effects of concurrent hypoxic/endurance training on mitochondrial respiration in permeabilized fibers in trained athletes were investigated . Eighteen endurance athletes were divided into two training groups :  normoxic ( Nor , n = 8) and hypoxic  ( H , n = 10 ) . Three weeks ( W1-W3 ) of endurance training ( 5 sessions of 1 h to 1 h and 30 min per week ) were completed . All training sessions were performed under normoxic [ 160 Torr inspired Po(2 ) ( Pi(O(2 ) ) ) ] or hypoxic conditions ( approximately 100 Torr Pi(O(2 ) ) , approximately 3,000 m ) for Nor and H group , respectively , at the same relative intensity . Before and after the training period , an incremental test to exhaustion in normoxia was performed , muscle biopsy sample s were taken from the vastus lateralis , and mitochondrial respiration in permeabilized fibers was measured . Peak power output ( PPO ) increased by 7.2 % and 6.6 % ( P < 0.05 ) for Nor and H , respectively , whereas maximal O(2 ) uptake ( Vo(2 max ) ) remained unchanged : 58.1 + /- 0.8 vs. 61.0 + /- 1.2 ml.kg(-1).min(-1 ) and 58.5 + /- 0.7 vs. 58.3 + /- 0.6 ml.kg(-1).min(-1 ) for Nor and H , respectively , between pretraining ( W0 ) and posttraining ( W4 ) . Maximal ADP-stimulated mitochondrial respiration significantly increased for glutamate + malate ( 6.27 + /- 0.37 vs. 8.51 + /- 0.33 mumol O(2).min(-1).g dry weight(-1 ) ) and significantly decreased for palmitate + malate ( 3.88 + /- 0.23 vs. 2.77 + /- 0.08 mumol O(2).min(-1).g dry weight(-1 ) ) in the H group . In contrast , no significant differences were found for the Nor group . The findings demonstrate that 1 ) a 3-wk training period increased the PPO at sea level without any changes in Vo(2 max ) , and 2 ) a 3-wk hypoxic exercise training seems to alter the intrinsic properties of mitochondrial function , i.e. , substrate preference Inspiring a hyperoxic ( H ) gas permits subjects to exercise at higher power outputs while training , but there is controversy as to whether this improves skeletal muscle oxidative capacity , maximal O(2 ) consumption ( Vo(2 max ) ) , and endurance performance to a greater extent than training in normoxia ( N ) . To determine whether the higher power output during H training leads to a greater increase in these parameters , nine recreationally active subjects were r and omly assigned in a single-blind fashion to train in H ( 60 % O(2 ) ) or N for 6 wk ( 3 sessions/wk of 10 x 4 min at 90 % Vo(2 max ) ) . Training heart rate ( HR ) was maintained during the study by increasing power output . After at least 6 wk of detraining , a second 6-wk training protocol was completed with the other breathing condition . Vo(2 max ) and cycle time to exhaustion at 90 % of pretraining Vo(2 max ) were tested in room air pre- and posttraining . Muscle biopsies were sample d pre- and posttraining for citrate synthase ( CS ) , beta-hydroxyacyl-coenzyme A dehydrogenase ( beta-HAD ) , and mitochondrial aspartate aminotransferase ( m-AsAT ) activity measurements . Training power outputs were 8 % higher ( 17 W ) in H vs. N. However , both conditions produced similar improvements in Vo(2 max ) ( 11 - 12 % ) ; time to exhaustion ( approximately 100 % ) ; and CS ( H , 30 % ; N , 32 % ) , beta-HAD ( H , 23 % ; N , 21 % ) , and m-AsAT ( H , 21 % ; N , 26 % ) activities . We conclude that the additional training stimulus provided by training in H was not sufficient to produce greater increases in the aerobic capacity of skeletal muscle and whole body Vo(2 max ) and exercise performance compared with training in
This analysis indicates that the current body of literature does not support a de facto decrease of in vivo muscle oxidative capacity in old age .
The heterogeneity of study results and identification of significant moderators provide clarity regarding apparent discrepancies in the literature , and indicate the importance of accounting for these variables when examining purported age-related differences in muscle oxidative capacity
Despite intensive efforts to underst and the extent to which skeletal muscle mitochondrial capacity changes in older humans , the answer to this important question remains unclear .
To determine what the preponderance of evidence from in vivo studies suggests , we conducted a systematic review and meta- analysis of the effects of age on muscle oxidative capacity as measured noninvasively by magnetic resonance spectroscopy .
A secondary aim was to examine potential moderators contributing to differences in results across studies , including muscle group , physical activity status , and sex .