Prolonged Exercise Training Research Articles

Reduced AMPK-ACC and mTOR signaling in muscle from older men, and effect of resistance exercise

AMP-activated protein kinase (AMPK) is a key energy-sensitive enzyme that controls numerous metabolic and cellular processes. Mammalian target of rapamycin (mTOR) is another energy/nutrient-sensitive kinase that controls protein synthesis and cell growth. In this study we determined whether older versus younger men have alterations in the AMPK and mTOR pathways in skeletal muscle, and examined the effect of a long term resistance type exercise training program on these signaling intermediaries. Older men had decreased AMPKα2 activity and lower phosphorylation of AMPK and its downstream signaling substrate acetyl-CoA carboxylase (ACC). mTOR phosphylation also was reduced in muscle from older men. Exercise training increased AMPKα1 activity in older men, however, AMPKα2 activity, and the phosphorylation of AMPK, ACC and mTOR, were not affected. In conclusion, older men have alterations in the AMPK-ACC and mTOR pathways in muscle. In addition, prolonged resistance type exercise training induces an isoform-selective up regulation of AMPK activity.

Prolonged exercise training increases intramuscular lipid content and perilipin 2 expression in type I muscle fibers of patients with type 2 diabetes

The aim of the present study was to investigate changes in intramuscular triglyceride (IMTG) content and perilipin 2 expression in skeletal muscle tissue following 6 mo of endurance-type exercise training in type 2 diabetes patients. Ten obese male type 2 diabetes patients (age 62 ± 1 yr, body mass index BMI 31 ± 1 kg/m²) completed three exercise sessions/week consisting of 40 min of continuous endurance-type exercise at 75% V(O₂ peak) for a period of 6 mo. Muscle biopsies collected at baseline and after 2 and 6 mo of intervention were analyzed for IMTG content and perilipin 2 expression using fiber type-specific immunofluorescence microscopy. Endurance-type exercise training reduced trunk body fat by 6 ± 2% and increased whole body oxygen uptake capacity by 13 ± 7% (P < 0.05). IMTG content increased twofold in response to the 6 mo of exercise training in both type I and type II muscle fibers (P < 0.05). A threefold increase in perilipin 2 expression was observed from baseline to 2 and 6 mo of intervention in the type I muscle fibers only (1.1 ± 0.3, 3.4 ± 0.6, and 3.6 ± 0.6% of fibers stained, respectively, P < 0.05). Exercise training induced a 1.6-fold increase in mitochondrial content after 6 mo of training in both type I and type II muscle fibers (P < 0.05). In conclusion, this is the first study to report that prolonged endurance-type exercise training increases the expression of perilipin 2 alongside increases in IMTG content in a type I muscle fiber-type specific manner in type 2 diabetes patients.

Murine double minute‐2 expression is required for capillary maintenance and exercise‐induced angiogenesis in skeletal muscle

Exercise-induced angiogenesis is a key determinant of skeletal muscle function. Here, we investigated whether the E3 ubiquitin ligase murine double minute-2 (Mdm2) exerts a proangiogenic function in exercised skeletal muscle. Mdm2 hypomorphic (Mdm2(Puro/Δ7-9)) mice have a 60% reduction in Mdm2 expression compared with that in wild-type animals. Capillary staining on muscle sections from Mdm2(Puro/Δ7-9) sedentary mice with a wild-type or knockout background for p53 revealed that deficiency in Mdm2 resulted in 20% capillary regression independently of p53 status. In response to one bout of exercise, protein expression of the proangiogenic vascular endothelial growth factor-A (VEGF-A) was increased by 64% in muscle from wild-type animals, and endothelial cell outgrowth from exercised muscle biopsy samples cultured in a 3-dimensional collagen gel was enhanced by 37%. These proangiogenic responses to exercise were impaired in exercised Mdm2(Puro/Δ7-9) mice. Prolonged exercise training resulted in increased Mdm2 protein expression (+49%) and capillarization (+24%) in wild-type muscles. However, exercise training-induced angiogenesis was abolished in Mdm2(Puro/Δ7-9) mice. Finally, exercise training restored Mdm2, VEGF-A, and capillarization levels in skeletal muscles from obese Zucker diabetic fatty rats compared with those in healthy animals. Our results define Mdm2 as a crucial regulator of capillary maintenance and exercise-induced angiogenesis in skeletal muscle.

Physical Activity Is the Key Determinant of Skeletal Muscle Mitochondrial Function in Type 2 Diabetes

Conflicting data exist on mitochondrial function and physical activity in type 2 diabetes mellitus (T2DM) development. The aim was to assess mitochondrial function at different stages during T2DM development in combination with physical exercise in longstanding T2DM patients. We performed cross-sectional analysis of skeletal muscle from 12 prediabetic 11 longstanding T2DM male subjects and 12 male controls matched by age and body mass index. One-year intrasubject controlled supervised exercise training intervention was done in longstanding T2DM patients. Extensive ex vivo analyses of mitochondrial quality, quantity, and function were collected and combined with global gene expression analysis and in vivo ATP production capacity after 1 yr of training. Mitochondrial density, complex I activity, and the expression of Krebs cycle and oxidative phosphorylation system-related genes were lower in longstanding T2DM subjects but not in prediabetic subjects compared with controls. This indicated a reduced capacity to generate ATP in longstanding T2DM patients only. Gene expression analysis in prediabetic subjects suggested a switch from carbohydrate toward lipid as an energy source. One year of exercise training raised in vivo skeletal muscle ATP production capacity by 21 ± 2% with an increased trend in mitochondrial density and complex I activity. In addition, expression levels of β-oxidation, Krebs cycle, and oxidative phosphorylation system-related genes were higher after exercise training. Mitochondrial dysfunction is apparent only in inactive longstanding T2DM patients, which suggests that mitochondrial function and insulin resistance do not depend on each other. Prolonged exercise training can, at least partly, reverse the mitochondrial impairments associated with the longstanding diabetic state.

Protein Supplementation Increases Muscle Mass Gain During Prolonged Resistance-Type Exercise Training in Frail Elderly People: A Randomized, Double-Blind, Placebo-Controlled Trial

Protein supplementation has been proposed as an effective dietary strategy to augment the skeletal muscle adaptive response to prolonged resistance-type exercise training in elderly people. Our objective was to assess the impact of protein supplementation on muscle mass, strength, and physical performance during prolonged resistance-type exercise training in frail elderly men and women. A randomized, double-blind, placebo-controlled trial with 2 arms in parallel among 62 frail elderly subjects (78 ± 1 year). These elderly subjects participated in a progressive resistance-type exercise training program (2 sessions per week for 24 weeks) during which they were supplemented twice daily with either protein (2 * 15 g) or a placebo. Lean body mass (DXA), strength (1-RM), and physical performance (SPPB) were assessed at baseline, and after 12 and 24 weeks of intervention. Lean body mass increased from 47.2 kg (95% CI, 43.5-50.9) to 48.5 kg (95% CI, 44.8-52.1) in the protein group and did not change in the placebo group (from 45.7 kg, 95% CI, 42.1-49.2 to 45.4 kg, 95% CI, 41.8-48.9) following the intervention (P value for treatment × time interaction = .006). Strength and physical performance improved significantly in both groups (P = .000) with no interaction effect of dietary protein supplementation. Prolonged resistance-type exercise training represents an effective strategy to improve strength and physical performance in frail elderly people. Dietary protein supplementation is required to allow muscle mass gain during exercise training in frail elderly people. clinicaltrials.gov identifier: NCT01110369.

The Morganroth hypothesis revisited: endurance exercise elicits eccentric hypertrophy of the heart

The Morganroth hypothesis revisited: endurance exercise elicits eccentric hypertrophy of the heart

Prolonged endurance exercise decreases fiber loss and fiber atrophy in aged male rats

Sarcopenia is the age‐related loss of muscle mass and function. Effects of long‐term exercise training on sarcopenia have not been well defined. In this study we assessed skeletal muscle adaptations to prolonged exercise training in rats from late‐middle age to old age. Male rats, 24 mo of age, trained on a treadmill at three levels of intensity: high (HI: 13m/min, 5% incline for 30 min, 5 days per week), moderate (MI: 13m/min, 0% incline for 30 min, 5 days per week), minimally active (MA: 5m/min, for 5 min, 2 days per week) and a sedentary group (S). Rats ran for one year until the rats were age 36 months. The rectus femoris (RF) muscle from 24‐month Controls (C), and 36‐month HI, MI, MA, and S. The RF was weighed, bisected, frozen, sectioned and stained with hematoxylin and eosin. Digital images of RF cross‐sections were used to determine muscle area, fiber number and fiber diameter. Aging significantly reduced muscle mass, muscle area, fiber number and fiber diameter, (24‐month C compared to any of the 36‐month old S, MA, MI or HI). Among the 36‐mo. rats (HI, MI, MA, and S), no differences were observed in muscle mass or muscle area. However, there was a significant increase in fiber number and fiber diameter in all exercise groups (HI, MI, and MA) compared to S. These results indicate that any level of exercise, even minimal levels of activity is capable of decreasing the effects of sarcopenia in aging rats.Supported by NIH AG 030423.

Role of sirtuins, calorie restriction and physical activity in aging

Recently it has been discovered that Sirtuins represent pivotal regulators of lifespan. Caloric restriction (CR) enhances longevity from yeast to mammals. Whereas the relationship between Sirt-1 and CR is clear, the molecular mechanisms by which Sir2 increases longevity are still unknown. In mammals, CR induces physiological and behavioral changes, and many studies have shown that CR decreases production of reactive oxygen species production thus minimizing oxidative damage, leading to the hypothesis that CR by reducing oxidative stress extends the lifespan by counteraction of aging. In fact, the pathophysiology of aging and age-related diseases involves oxidative stress as an early stage in its development. Recently we found that in aged rats the SIRT1 activity was decreased in heart and adipose tissue, showing as aging is characterized in vivo by a reduced efficiency of this key-regulator of longevity. Whereas several studies have reported that increased physical activity can improve mean life span presumably by reducing mortality risk from many age-related diseases, exercise and longevity studies have failed to document an exercise effect on maximum life span. However, in aged rats a moderate prolonged exercise training is able to induce increase in SIRT1 activity, suggesting that this tool could counteract age-related dysfunctions.

Changes in Arginase-Nitric Oxide Synthase System at Adaptation to Prolonged Exercise Training by Swimming in Adult and Aged Rat Hearts

We studied the contractile activity of isolated hearts from adult rats adapted to prolonged exercise training by swimming. It has been shown that stimulation of NO production in the mitochondrial compartment of the heart from trained adult rats resulted in the left ventricular force increase, the myocardial stiffness decrease, and both systolic and diastolic heart function improvement. In the heart mitochondria of adult rats trained by swimming, an activation of all examined enzymes of nitric oxide synthesis, namely, inducible, constitutive NO-synthase (de novo synthesis) and nitrate reductase (nonoxidative salvage synthesis) has been established, whereas in old animals, only oxidative enzymes of de novo pathways were stimulated. Exercise training significantly reduced the mitochondrial pools of nitrate anion in adult rats, while in old ones the contents of urea, nitrite anion pools did not change in that situation. Mitochondrial H2O2 pools after training in adult rats increased, while in the old animals those pools, conversely, decreased. Exercise training resulted in a significant increase in oxygenation index in the mitochondria of adult rats and a decrease in the activity of mitochondrial arginase II. The results give reason to believe that swimming as a physical training stimulates N0 production in the mitochondria of adult and old rats, and therefore, it can be considered effective non-pharmacological correction of the age-specific dysfunction of the heart.

Role of PGC-1α in exercise and fasting-induced adaptations in mouse liver

The transcriptional coactivator peroxisome proliferator-activated receptor (PPAR)-γ coactivator (PGC)-1α plays a role in regulation of several metabolic pathways. By use of whole body PGC-1α knockout (KO) mice, we investigated the role of PGC-1α in fasting, acute exercise and exercise training-induced regulation of key proteins in gluconeogenesis and metabolism in the liver. In both wild-type (WT) and PGC-1α KO mice liver, the mRNA content of the gluconeogenic proteins glucose-6-phosphatase (G6Pase) and phosphoenolpyruvate carboxykinase (PEPCK) was upregulated during fasting. Pyruvate carboxylase (PC) remained unchanged after fasting in WT mice, but it was upregulated in PGC-1α KO mice. In response to a single exercise bout, G6Pase mRNA was upregulated in both genotypes, whereas no significant changes were detected in PEPCK or PC mRNA. While G6Pase and PC protein remained unchanged, liver PEPCK protein content was higher in trained than untrained mice of both genotypes. The mRNA content of the mitochondrial proteins cytochrome c (Cyt c) and cytochrome oxidase (COX) subunit I was unchanged in response to fasting. The mRNA and protein content of Cyt c and COXI increased in the liver in response to a single exercise bout and prolonged exercise training, respectively, in WT mice, but not in PGC-1α KO mice. Neither fasting nor exercise affected the mRNA expression of antioxidant enzymes in the liver, and knockout of PGC-1α had no effect. In conclusion, these results suggest that PGC-1α plays a pivotal role in regulation of Cyt c and COXI expression in the liver in response to a single exercise bout and prolonged exercise training, which implies that exercise training-induced improvements in oxidative capacity of the liver is regulated by PGC-1α.

Skeletal muscle mitochondrial dysfunction is secondary to type 2 diabetes and can be improved by prolonged exercise training

Skeletal muscle mitochondrial dysfunction is secondary to type 2 diabetes and can be improved by prolonged exercise training

Chronic AICAR treatment, but not voluntary exercise training, increases nicotinamide phosphoribosyl transferase (Nampt) protein expression in an AMPK‐dependent manner in mouse quadriceps muscle

Nampt regulates intracellular NAD+ levels and may modulate sirtuin activity. AMP-activated protein kinase (AMPK) may regulate Nampt expression in skeletal muscle. We investigated whether chronic endurance exercise or treatment with aminoimidazole carboxamide ribonucleotide (AICAR) alter skeletal muscle Nampt concentrations in an AMPK-dependent fashion. Whole-body AMPK α2 (catalytic subunit) KO mice and WT littermates (n=9–11) were injected subcutaneously with AICAR or saline for 28 d (500 mg/kg body weight). Separately, WT and α2 KO animals (n=10–16) performed voluntary wheel-cage exercise for 28 d or served as sedentary controls. Animals were sacrificed 24 h after the last AICAR injection or 14–16 h after the last exercise bout. Nampt protein expression in quadriceps muscle was assessed via immunoblots. Running distance was similar between WT (3.98 ± 0.34 km; mean ± S.E.M.) and AMPK α2 KO mice (4.59 ± 0.36 km). Nampt expression did not change with training, but was lower in sedentary and trained α2 KO mice by 22 and 13 %, respectively (main effect, p<0.05). In the cohort receiving saline or AICAR, Nampt was also significantly (main effect, p<0.05) lower in the α2 KO mice. AICAR treatment increased Nampt expression in WT mice by 25% (p<0.05); this effect was completely abolished in the α2 KO animals. In conclusion, whole-body knockout of the AMPK α2 catalytic subunit reduces Nampt expression in mouse skeletal muscle. Furthermore, chronic AICAR treatment, but not prolonged exercise training increases Nampt protein expression in an AMPK α2-dependent manner.

PP230-SUN THE EFFECTS OF PROTEIN SUPPLEMENTATION DURING PROLONGED RESISTANCE TYPE EXERCISE TRAINING ON MUSCLE MASS AND FUNCTION IN FRAIL ELDERLY

PP230-SUN THE EFFECTS OF PROTEIN SUPPLEMENTATION DURING PROLONGED RESISTANCE TYPE EXERCISE TRAINING ON MUSCLE MASS AND FUNCTION IN FRAIL ELDERLY

Prolonged exercise training induces long-term enhancement of HSP70 expression in rat plantaris muscle

Skeletal muscle may develop adaptive molecular chaperone enhancements as a potential defense system through repeated daily exercise stimulation. The present study investigated whether prolonged exercise training alters the expression of molecular chaperone proteins for the long term in skeletal muscle. Mature male Wistar rats were subjected for 8 wk to either a single bout of acute intermittent treadmill running (30 m/min, 5 min x 4, 5 degrees grade) or prolonged treadmill running training (15-40 m/min, 5 min x 4, 5-7 degrees grade). Levels of five molecular chaperone proteins [heat shock protein (HSP)25, HSP60, glucose-regulated protein (GRP)78, HSP70, and heat shock cognate (HSC)70] were measured in response to acute exercise and prolonged training. HSP70 levels were increased 6 and 24 h after acute exercise, but expression returned to control level within 2 days. In contrast, prolonged training had a long-term effect on HSP70 expression. Levels of HSP70 were notably increased by 4.5-fold over control 2 days after prolonged training; the enhancement was maintained for at least 14 days after training ended. However, other molecular chaperone proteins did not show adaptive changes in response to prolonged training. In addition, HSP70 enhancement by prolonged exercise training was not accompanied by transcription of HSP70 mRNA. These findings demonstrate that prolonged training can induce long-term enhancement of HSP70 expression without change at the mRNA level in skeletal muscle.

Protein supplementation before and after exercise does not further augment skeletal muscle hypertrophy after resistance training in elderly men

Background:Considerable discrepancy exists in the literature on the proposed benefits of protein supplementation on the adaptive response of skeletal muscle to resistance-type exercise training in the elderly.Objective: The objective was to assess the benefits of timed protein supplementation on the increase in muscle mass and strength during prolonged resistance-type exercise training in healthy elderly men who habitually consume adequate amounts of dietary protein.Design: Healthy elderly men (n = 26) aged 72 ± 2 y were randomly assigned to a progressive, 12-wk resistance-type exercise training program with (protein group) or without (placebo group) protein provided before and immediately after each exercise session (3 sessions/wk, 20 g protein/session). One-repetition maximum (1RM) tests were performed regularly to ensure a progressive workload during the intervention. Muscle hypertrophy was assessed at the whole-body (dual-energy X-ray absorptiometry), limb (computed tomography), and muscle fiber (biopsy) level.Results: The 1RM strength increased ≈25–35% in both groups (P < 0.001). Dual-energy X-ray absorptiometry and computed tomography scans showed similar increases in leg muscle mass (6 ± 1% in both groups; P < 0.001) and in the quadriceps (9 ± 1% in both groups), from 75.9 ± 3.7 and 73.8 ± 3.2 to 82.4 ± 3.9 and 80.0 ± 3.0 cm2 in the placebo and protein groups, respectively (P < 0.001). Muscle fiber hypertrophy was greater in type II (placebo: 28 ± 6%; protein: 29 ± 4%) than in type I (placebo: 5 ± 4%; protein: 13 ± 6%) fibers, but the difference between groups was not significant.Conclusion: Timed protein supplementation immediately before and after exercise does not further augment the increase in skeletal muscle mass and strength after prolonged resistance-type exercise training in healthy elderly men who habitually consume adequate amounts of dietary protein. This trial was registered at clinicaltrials.gov as NCT00744094.

Aging, exercise, and muscle protein metabolism

Aging is accompanied by a progressive loss of skeletal muscle mass and strength, leading to the loss of functional capacity and an increased risk of developing chronic metabolic disease. The age-related loss of skeletal muscle mass is attributed to a disruption in the regulation of skeletal muscle protein turnover, resulting in an imbalance between muscle protein synthesis and degradation. As basal (fasting) muscle protein synthesis rates do not seem to differ substantially between the young and elderly, many research groups have started to focus on the muscle protein synthetic response to the main anabolic stimuli, i.e., food intake and physical activity. Recent studies suggest that the muscle protein synthetic response to food intake is blunted in the elderly. The latter is now believed to represent a key factor responsible for the age-related decline in skeletal muscle mass. Physical activity and/or exercise stimulate postexercise muscle protein accretion in both the young and elderly. However, the latter largely depends on the timed administration of amino acids and/or protein before, during, and/or after exercise. Prolonged resistance type exercise training represents an effective therapeutic strategy to augment skeletal muscle mass and improve functional performance in the elderly. The latter shows that the ability of the muscle protein synthetic machinery to respond to anabolic stimuli is preserved up to very old age. Research is warranted to elucidate the interaction between nutrition, exercise, and the skeletal muscle adaptive response. The latter is needed to define more effective strategies that will maximize the therapeutic benefits of lifestyle intervention in the elderly.

Effects of endurance exercise on ventral tegmental area neurons in the chronic 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and probenecid-treated mice

Loss of dopaminergic neurons in the substantia nigra (A9 cells) and ventral tegmental area (VTA) (A10 cells) has been reported in Parkinson's disease with reference to causing motor and non-motor deficits, although clinical and laboratory animal studies on the degeneration of VTA neurons are less emphasized comparative to the degeneration of substantia nigra neurons. In the present study, we examined the VTA dopaminergic neurons in a chronic mouse model of Parkinson's disease induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and probenecid at a level showing moderate neurodegeneration and studied the impact of endurance exercise on VTA neurons in this model. In comparison to the normal control animals, the chronic mouse model of Parkinson's disease with moderate neurodegeneration demonstrated a significant reduction of VTA neurons (52% loss), when these animals were kept sedentary throughout the study. Morphologically, the VTA dopaminergic neurons in this model displayed a decrease in cell volume and showed irregular or disparaging axonal and dendritic projections. When the chronic Parkinsonian mice were exercised on a motorized rodent treadmill up to 15m/min, 40min/day, 5 days/week for 10 and 18 weeks, the total number of VTA dopaminergic neurons were significantly higher than the sedentary Parkinsonian animals. Especially noted with the 18-week exercised Parkinsonian mice, the number of VTA neurons returned to normal range and the cells were densely populated and displayed distinctive axons and dendritic arborization. These results demonstrate that prolonged exercise training is neuroprotective to the dopaminergic neurons in the VTA of the chronic mouse model of Parkinson's disease with moderate neurodegeneration.

Oxidative Stress Mechanisms During Intermittent Exercise in Normal and Overweight Children

While intense exercise can acutely increase oxidative stress, prolonged exercise training has been shown to protect against oxidative stress and cardiovascular disease in adult populations. As oxidative stress has also been associated with obesity, exercise regimens are regularly utilized as preventive tools in this condition. However, the regulation of oxidative processes during exercise remains poorly defined in obese populations, and virtually no data are available for children. PURPOSE: We therefore examined key oxidative stress variables in healthy and overweight children during intense intermittent exercise. METHODS: 66 peri-pubertal children (35 normal weight, NW, 13.5 ± 0.5 yrs, 23F, BMI % 58 ± 4, tanner 3.1 ± 0.2; 31 overweight, OW, 12.2 ± 0.5 yrs, 13F, BMI % 96 ± 1, tanner 2.9 ± 0.2) performed 10 bouts of 2-min cycling at ~80% VO2max, separated by 1-min rest intervals. Blood samples were drawn at baseline and end-exercise. FU1 RESULTS: The OW group, as compared to NW, had higher 8-iso-PGF2 at baseline (2310 ± 134 vs 714 ± 201 pg/mL, p<0.02), myeloperoxidase (MPO) at end-exercise (121 ± 40 vs 21 ± 5 ng/mL, p<0.01), catalase both at baseline (169 ± 15 vs 115 ± 9 U/mg/mL, p<0.003) and end-exercise (199 ± 24 vs 112 ± 15, p<0.003), and lower total glutathione at both baseline (212 ± 16 vs 321 ± 20 uM, p<0.0001) and endexercise 229 ± 18 vs 304 ± 20, p<0.01. CONCLUSIONS: Our data show that oxidative processes markedly differ in NW and OW children during exercise, possibly altering the full potential benefits of exercise in the OW group. Our data stress the concept that the optimization of exercise regimens in the obese child will require a deeper understanding of all related adaptive mechanisms. Supported by NIH grants M01-RR00827-28 and P01HD048721-01A1.

Markers of Mitochondrial Biogenesis following 3 days of Cycling

Exercise increases mRNA for several genes involved in mitochondrial biogenesis. Less is known about how these genes respond to several successive days of intensive exercise.PURPOSE:To examine the effects of 3 h of intensive cycling over 3 successive days on gene expression in humans.METHODS:Twenty trained cyclists were tested for VO2max (54.7±1.1 ml.kg‐1.min‐1). The subjects cycled at 57% wattsmax for 3 h using their own bicycles on CompuTrainer™ Pro Model trainers (RacerMate, Seattle, WA) on 3 successive days. Muscle biopsies were obtained from the vastus lateralis pre‐ and post‐exercise on days 1 and 3. Muscle samples were analyzed (2(time) X 2(day) repeated measures ANOVA) for gene expression of cytochrome C, peroxisome proliferator receptor gamma coactivator‐1 alpha (PGC‐1A), citrate synthase, and Sirt‐1.RESULTS:Of the genes analyzed the following showed significant increases pre‐post 3 h rides: cytochrome C (P=0.03), PGC‐1A (P&lt;0.001), and Sirt‐1 (P=0.05). The following genes showed significant effects from days 1 to 3: cytochrome C (P&lt;0.001) and citrate synthase (P=0.009).CONCLUSION:Three successive days of intensive cycling resulted in upregulation of mRNA for mitochondrial enzymes and biogenesis markers in these trained subjects. These data contribute to the understanding of mitochondrial enzyme expression during prolonged exercise training.

Prolonged Exercise Training does not Preserve Mitochondrial Enzyme Activity in Senescent Rats

Skeletal muscle aerobic function (VO2max) and mitochondrial oxidative capacity decline with aging, particularly in senescence (SEN). Since exercise training improves muscle VO2max and oxidative capacity in young adult skeletal muscle, our objective was to determine if treadmill training from late middle age (LMA) into SEN would minimize the declines in skeletal muscle aerobic function and oxidative capacity seen in SEN. 62 male rats at late middle age (29 mo) were randomly separated into control and exercise groups. Exercise consisted of 60 m/day treadmill running, 5 d/week for 7 weeks and then decreased to 4 d/week for a total of 5 and 7 mo (until 34 and 36 mo of age respectively). Although running capacity was significantly higher in the trained groups (13% at 34 mo and 21% at 36 mo), muscle VO2max at matched muscle O2 delivery was not significantly greater in the trained groups compared to sedentary controls at either age. Similarly, citrate synthase and cytochrome oxidase activity in the plantaris, soleus and the heart muscle were not different in the trained vs the sedentary groups, suggesting no benefit of training for muscle oxidative capacity. The superior exercise capacity suggests a better overall level of function of the senescent rats; however, contrary to our hypothesis and prior observations in LMA rats, treadmill exercise training between LMA and SEN does not benefit muscle aerobic function or mitochondrial oxidative capacity.Supported by CIHR (AB, RT), CIHR Provincial Training Program in Bone and Joint Health (AB), AHFMR (RT) and NSERC (MT).