Absence of left ventricular and arterial adaptations to exercise in octogenarians.

Recent evidence suggests that octogenarians exhibit attenuated adaptations to training with a small increase in peak O2 consumption (VO2) that is mediated by a modest improvement in cardiac output without an increase in arteriovenous O2 content difference. This study was designed to determine whether diminished increases in peak VO2 and cardiac output in the octogenarians are associated with absence of left ventricular and arterial adaptations to exercise training. We studied 22 octogenarians (81.9 +/- 3.7 yr, mean +/- SD) randomly assigned a group that exercised at an intensity of 82.5 +/- 5% of peak heart rate for 9 mo and 14 (age 83.1 +/- 4.1) assigned to a control group. Peak VO2 increased 12% in the exercise group but decreased slightly (-7%) in the controls. The exercise group demonstrated significant but small decreases in the heart rate (6%, P = 0.002) and the rate-pressure product (9%, P = 0.004) during submaximal exercise at an absolute work rate. Training induced no significant changes in the left ventricular size, geometry (wall thickness-to-radius ratio), mass, and function assessed with two-dimensional echocardiography or in arterial stiffness evaluated with applanation tonometry. Data suggest that the absence of cardiac and arterial adaptations may in part account for the limited gain in aerobic capacity in response to training in the octogenarians.     

Postural specificity of cardiovascular adaptations to exercise training

The purposes of this study were to determine 1) whether posture affects the magnitude of cardiovascular adaptations to training and 2) whether cardiovascular adaptations resulting from exercise training in the supine posture transfer (generalize) to exercise in the upright posture and vice versa. Sixteen sedentary men, aged 18-33 yr, were trained using high-intensity interval and prolonged continuous cycling in the supine (STG; supine training group) or upright (UTG; upright training group) posture 4 days/wk, 40 min/day, for 8 wk, while seven male subjects served as nontraining controls. After training, maximal O2 uptake measured during supine and upright cycling, respectively, increased significantly (P less than 0.05) by 22.9 and 16.1% in the STG and by 6.0 and 14.6% in the UTG. No significant cardiovascular adaptations were observed at rest. During submaximal supine cycling at 100 W, significant increases in end-diastolic volume (21%) and stroke volume (22%) (radionuclide ventriculography and CO2 rebreathing) and decreases in heart rate, blood pressure, and systemic vascular resistance occurred in the STG, whereas only a significant decrease in blood pressure occurred in the UTG. During upright cycling at 100 W, a significant decrease in blood pressure occurred in the STG, whereas significant increases in end-diastolic volume (17%) and stroke volume (18%) and decreases in blood pressure and systemic vascular resistance occurred in the UTG. Volume of myocardial contractility, ejection fraction, and systolic blood pressure-to-end-systolic volume ratio did not change significantly after training when measured during supine and upright cycling in either training group. Blood volume increased significantly in the UTG but remained unchanged in the STG.(ABSTRACT TRUNCATED AT 250 WORDS)     

Hepatic adaptations to iron deficiency and exercise training.

Brooks et al. [Am. J. Physiol. 253 (Endocrinol. Metab. 16): E461-E466, 1987] demonstrated an elevated gluconeogenic rate in resting iron-deficient rats. Because physical exercise also imposes demand on this hepatic function, we hypothesized that exercise training superimposed on iron deficiency would augment the hepatic capacity for amino acid transamination/deamination and pyruvate carboxylation. Sprague-Dawley rats (n = 32) were obtained at weaning (21 days of age) and randomly assigned to iron-sufficient (dietary iron = 60 mg iron/kg diet) or iron-deficient (3 mg iron/kg) dietary groups. Dietary groups were subdivided into sedentary and trained subgroups. Treadmill training was 4 wk in duration, 6 days/wk, 1 h/day, 0% grade. Treadmill speed was initially 26.8 m/min and was decreased to 14.3 m/min over the 4-wk training period. The mild exercise-training regimen did not affect any measured variable in iron-sufficient rats. In contrast, in iron-deficient animals, training increased endurance capacity threefold and reduced blood lactate and the lactate-to-alanine ratio during submaximal exercise by 34 and 27%, respectively. The mitochondrial oxidative capacity of gastrocnemius muscle was increased 46% by training. However, the oxidative capacity of liver was not affected by either iron deficiency or training. Maximal rates of pyruvate carboxylation and glutamine metabolism by isolated liver mitochondria were also evaluated. Iron deficiency and training interacted to increase pyruvate carboxylation by intact mitochondria. Glutamine metabolism was increased roughly threefold by iron deficiency alone, and training amplified this effect to a ninefold increase over iron-sufficient animals.(ABSTRACT TRUNCATED AT 250 WORDS)     

Cardiopulmonary adaptations to pneumonectomy in dogs. I. Maximal exercise performance.

Maximal exercise performance was evaluated in four adult foxhounds after right pneumonectomy (removal of 58% of lung) and compared with that in seven sham-operated control dogs 6 mo after surgery. Maximal O2 uptake (ml O2.min-1.kg-1) was 142.9 +/- 1.9 in the sham group and 123.0 +/- 3.8 in the pneumonectomy group, a reduction of 14% (P less than 0.001). Maximal stroke volume (ml/kg) was 2.59 +/- 0.10 in the sham group and 1.99 +/- 0.05 in the pneumonectomy group, a reduction of 23% (P less than 0.005). Lung diffusing capacity (DL(CO)) (ml.min-1.Torr-1.kg-1) reached 2.27 +/- 0.08 in the combined lungs of the sham group and 1.67 +/- 0.07 in the remaining lung of the pneumonectomy group (P less than 0.001). In the pneumonectomy group, DL(CO) of the left lung was 76% greater than that in the left lung of controls. Blood lactate concentration and hematocrit were significantly higher at exercise in the pneumonectomy group. We conclude that, in dogs after resection of 58% of lung, O2 uptake, cardiac output, stroke volume, and DL(CO) at maximal exercise were restricted. However, the magnitude of overall impairment was surprisingly small, indicating a remarkable ability to compensate for the loss of one lung. This compensation was achieved through the recruitment of reserves in DL(CO) in the remaining lung, the development of exercise-induced polycythemia, and the maintenance of a relatively large stroke volume in the face of an increased pulmonary vascular resistance.     

Cardiovascular adaptations to exercise training in the elderly

Maximal O2 uptake (VO2max) and left ventricular function decrease with age. Endurance exercise training of sufficient intensity, frequency, and duration increases VO2max in the elderly. The mechanisms underlying the increased VO2max in the elderly are enhanced O2 extraction of trained muscle during maximal exercise leading to a wider arteriovenous O2 difference, and higher cardiac output in the trained state. However, increased cardiac output during true maximal exercise has not been documented in elderly subjects. Endurance exercise training results in a lower heart rate and rate pressure product during submaximal exercise at a given intensity. However, no improvement in left ventricular function has been reported in the elderly after exercise training. Highly trained master athletes exhibit proportional increases in the left ventricular end-diastolic dimension and wall thickness suggestive of volume-overload hypertrophy compared with age-matched sedentary controls. The magnitude of left ventricular enlargement is similar to that in young athletes. The failure of exercise training to alter the age-related deterioration of left ventricular function in the elderly may reflect an insufficient training stimulus rather than the inability of the heart to adapt to training in elderly subjects.     

Muscular adaptations to resistance exercise in the elderly

Neuropathic, metabolic, hormonal, nutritional and immunological factors contribute to the development of sarcopenia. This loss of muscle mass associated with ageing, is a main cause of muscle weakness, but the loss of muscle strength typically exceeds that of muscle size, with a resulting decrease in force per unit of muscle cross-sectional area. Recent evidence suggests that, in addition to a reduction in neural drive and in fibre specific tension, changes in muscle architecture contribute significantly to the loss of muscle force through alterations in muscle mechanical properties. Older muscle, however, maintains a high degree of plasticity in response to increased loading since considerable hypertrophy and a reversal of the alterations in muscle architecture associated with ageing are observed with resistive training.     

The mouse as a model of cardiovascular adaptations to microgravity.

There are a multitude of physiological adaptations to microgravity, involving the cardiovascular, neuromuscular, and neuroendocrine systems. Some of these adaptations lead to cardiovascular deconditioning on return to normal gravity, posing a threat to human functional integrity after long-term spaceflight. Animal models of microgravity, e.g., tail suspension in rats, have yielded important information regarding the mechanism of these adaptations and have been useful in the design of countermeasures. The mouse could potentially be a useful experimental model, given its small size (smaller and lighter payload) and the powerful tools of experimental mouse genetics, which allow us to dissect mechanisms on a gene-specific basis. We show that the mouse demonstrates a wide range of cardiovascular responses to simulated microgravity, including alterations in heart rate, exercise capacity, peripheral arterial vasodilatory responsiveness, and baroreflex response. These responses are qualitatively similar to many of those demonstrated in humans during spaceflight and in rats using tail suspension, although there are some important differences. Thus the mouse has value as a model for studies of cardiovascular changes during microgravity; however, investigators must maintain an appreciation of important species differences.     

Cardiovascular adaptations to 10days of cycle exercise

Mier, Constance M., Michael J. Turner, Ali A. Ehsani, andRobert J. Spina. Cardiovascular adaptations to 10 days of cycleexercise. J. Appl. Physiol. 83(6):1900-1906, 1997.We hypothesized that 10 days of training wouldenhance cardiac output (CO) and stroke volume (SV) during peak exerciseand increase the inotropic response to -adrenergic stimulation. Tensubjects [age 26 ± 2 (SE) yr] trained on a cycleergometer for 10 days. At peak exercise, training increasedO₂ uptake, CO, and SV(P < 0.001). Left ventricular (LV)size and function at rest were assessed with two-dimensional echocardiography before (baseline) and after atropine injection (1.0 mg) and during four graded doses of dobutamine. LV end-diastolic diameter increased with training (P < 0.02), whereas LV wall thickness was unchanged. LV contractileperformance was assessed by relating fractional shortening (FS) to theestimated end-systolic wall stress(_ES). Training increased theslope of the FS-_ES relationship (P < 0.05), indicating enhancedsystolic function. The increase in slope correlated with increases inCO (r = 0.71,P < 0.05) and SV(r = 0.70,P < 0.05). The increase in bloodvolume also correlated with increases in CO(r = 0.80, P < 0.01) and SV (r = 0.85, P < 0.004). These datashow that 10 days of training enhance the inotropic response to-adrenergic stimulation, associated with increases in CO and SVduring peak exercise.

     

Acute adaptations of the coronary circulation to exercise

Coronary blood flow is tightly coupled to myocardial oxygen consumption to maintain a consistently high level of myocardial oxygen extraction. This tight coupling has been proposed to depend on periarteriolar, oxygen tension, signals released from cardiomyocytes (adenosine acting on K _ATP ⁺ channels), and/or the endothelium (prostanoids, nitric oxide, endothelin [ET]) and autonomic influences (catecholamines), but the contribution of each of these regulatory pathways and their interactions are still incompletely understood. Until recently, experimental studies into the regulation of coronary blood flow during exercise were principally performed in the dog. We have performed several studies on the regulation of vasomotor tone in coronary resistance vessels in chronically instrumented exercising swine. These studies have shown that the coronary resistance vessels in swine lack significant α-adrenergic control, but that these vessels are subject to β-adrenergic feed-forward control during exercise, which is aided by a parasympathetic withdrawal. In addition, withdrawal of an ET-mediated vasoconstrictor influence also contributes to exercise-induced coronary vasodilation. Coronary blood flow regulation by endothelial and metabolic vasodilator pathways contributes to resting vasomotor tone regulation but does not appear to contribute to the exercise-induced coronary vasodilation. Furthermore, blockade of one vasodilator pathway is not compensated by an increased contribution of the other vasodilator mechanisms, suggesting that porcine coronary vasomotor control by endothelial and metabolic factors occurs in a linear additive rather than a nonlinear synergistic fashion.     

Control of adaptations in protein levels in response to exercise

The nature of the contractile stimuli to which a skeletal muscle is subjected determines which proteins will increase in skeletal muscle. Rates of muscle protein synthesis decrease during an exercise bout for durations of less than 30 min. Synthesis has been reported to increase, remain unchanged, or decrease during exercise bouts lasting from 30 min to 7 h. Protein synthesis rates apparently increase when exercise exceeds 7 h. After short bouts of exercise, protein synthesis rates in muscles appear to decrease in the first hour after exercise, but in the second hour after exercise increase to levels greater than normal. We hypothesize that decreases in ATP and pH levels in muscle during contractile activity may dampen a calcium-mediated stimulation of translation of RNA. That the content of alpha-actin mRNA in muscles of immobilized limbs is unchanged when actin synthesis initially decreases suggests that a decrease in the translation of alpha-actin mRNA is the facilitating step in the decrease in actin synthesis. Rates of muscle protein degradation decrease during exercise if exercise duration is less than 12 h, but increase when exercise is continuous for a day. After intense exercise, rates of protein degradation in skeletal muscle may be increased. An increased ratio of NAD(P)H:NAD(P) in muscle during short-term exercise may decrease degradation. Increased lysosomal enzyme activity in muscle occurs during the postexercise period.     

Functional adaptations of rat skeletal muscle arterioles to aerobic exercise training.

This study tested the hypothesis that both structural and functional adaptations of arterioles occur within the skeletal muscle of rats aerobically trained for 8-10 wk with treadmill exercise. The training regimen used has been shown to elicit a 37% increase in plantaris citrate synthase activity but did not result in an elevation in citrate synthase activity in the spinotrapezius or gracilis muscles of rats used in this study. In the in vivo resting spinotrapezius muscle, arteriole diameters were similar in sedentary (SED) and trained (TR) rats. However, large- (1A) and intermediate- (2A) sized arterioles dilated proportionately more in TR than in SED rats during 1- to 8-Hz muscle contractions, even though the passive mechanical properties (circumference-passive wall tension relationships) were similar between groups. Vascular casts demonstrated a trend for an increase in the number of small (3A) arterioles and an approximately 20% increase in the passive diameter of 1A and 2A arterioles in the spinotrapezius muscle of TR rats. In contrast, in the gracilis muscle, arteriole diameters and density were identical in SED and TR rats, but the capillary-to-muscle fiber ratio was approximately 15% higher in TR rats. The results suggest that aerobic exercise training can greatly increase functional vasodilation and induce a slight increase in vascular density in skeletal muscle tissues, even if the oxidative capacity of these tissues is not increased by the training regimen.     

Neuroplastic adaptations to exercise: neuronal remodeling in cardiorespiratory and locomotor areas.

Neuronal activity has been shown to be attenuated in cardiorespiratory and locomotor centers of the brain in response to a single bout of exercise in trained (TR) vs. untrained (UN) animals, but the mechanisms remain obscure. Based on this finding, dendritic branching patterns of seven brain areas associated with cardiorespiratory and locomotor activity were examined in TR and UN animals. Twenty-eight male Sprague-Dawley rats were kept in individual cages and divided into TR and UN. TR were provided with a running wheel and exercised spontaneously. After 85 or 120 days, exercise training indexes were obtained, including maximal oxygen consumption, percent body fat, resting heart rate, and heart weight-to-body weight ratios. The brain was removed and processed according to a modified Golgi-Cox procedure. Impregnated neurons from seven brain areas were examined in coronal sections: the periaqueductal gray, posterior hypothalamic area, nucleus of the tractus solitarius, rostral ventrolateral medulla, cuneiform nucleus, nucleus cuneatus, and cerebral cortex. Neurons were traced using a camera lucida technique and analyzed using the Sholl analysis of dendritic branching. t-tests were conducted to compare the mean number of intersections per neuron by grouping inner rings and outer rings and also comparing the total number of intersections per animal. There were significant differences between groups in the posterior hypothalamic area, periaqueductal gray, cuneiform nucleus, and nucleus of the tractus solitarius in the inner rings, outer rings, and the total number of intersections per animal. Our results show that dendritic fields of neurons in important cardiorespiratory and locomotor centers of the brain are attenuated in TR animals.     

Intramuscular adaptations to eccentric exercise and antioxidant supplementation

Prophylactic supplementation of N-acetyl-cysteine (NAC) and epigallocatechin gallate (EGCG) was studied for physiological and cellular changes in skeletal muscle after eccentric muscle contractions. Thirty healthy, active males (20.0 ± 1.8 years, 160 ± 7.1 cm, 76.1 ± 17.0 kg) ingested for 14 days either 1,800 mg of NAC, 1,800 mg of EGCG, or 1,000 mg of fiber (glucomannan) placebo (PLC) in a double blind, prophylactic fashion. Subjects completed one eccentric exercise bout (100 repetitions at 30°/s) using the dominant knee extensors. Strength and soreness were assessed, and blood and muscle samples obtained before and 6, 24, 48, and 72 h with no muscle sample being collected at 72 h. Separate mixed factorial repeated measures ANOVA (P < 0.05) were used for all statistical analysis. All groups experienced significantly reduced peak torque production after 6 and 24 h, increased soreness at all time points from baseline [with even greater soreness levels 24 h after exercise in PLC when compared to EGCG and NAC (P < 0.05)], increased lactate dehydrogenase at 6 h, and increased creatine kinase 6, 24 and 48 h after exercise. No significant group × time interaction effects were found for serum cortisol, neutrophil counts, and the neutrophil:lymphocyte ratio; although, all values experienced significant changes 6 h after exercise (P < 0.05), but at no other time points. At 48 h after the exercise bout the Neu:Lym ratio in EGCG was significantly less than NAC (P < 0.05), whereas there was a trend (P = 0.08) for the EGCG values to be less when compared to PLC at this time point. Markers of intramuscular mitochondrial and cytosolic apoptosis were assessed (e.g., bax, bcl-2, cytochrome C, caspase-3 content/enzyme activity, and total DNA content). Significant increases (P < 0.05) in muscle levels of bax and bcl-2 were observed in all groups with no significant differences between groups, whereas no changes (P > 0.05) were reported for cytochrome C, caspase-3 content, caspase-3 enzyme activity, and total DNA. Caspase-3 enzyme activity was significantly greater in all groups 48 h after exercise when compared to baseline (P < 0.05) and 6 h (P < 0.05) after exercise. An eccentric bout of muscle contractions appears to significantly increase muscle damage, markers of mitochondrial apoptosis, apoptotic enzyme activity, and whole-blood cell markers of inflammation with no changes in oxidative stress. While soreness ratings were blunted in the two supplementation groups 24 h after exercise when compared to PLC values, more research is needed to determine the potential impact of EGCG and NAC supplementation on changes related to oxidative stress, apoptosis, and eccentric exercise.     

Physiological adaptations to exercise in people with spinal cord injury

The number of patients that suffer some type of spinal cord lesion in recent years are high and have increased because of factors such as traffic accidents. Although their life expectancy has increased, cardiovascular illnesses is one of the main causes of morbidity and mortality. Since the degree of physical fitness is an important factor regarding the risk of cardiovascular disease, the objective of the present study was to examine the global adaptation (cardiorespiratory, metabolic and thermoregulatory response) of the organism to exercise and the application of this data to the habitual practice of physical activity to improve state of health. A group of 42 patients with spinal injury, 85% of whom were paraplegic and the remaining 15% tetraplegic performed 42 exercise tests on a cycloergometer. Body temperature (tympanum, surface of the deltoids and surface of the back), metabolic parameters (plasma uric acid, glycemia, plasma lactate), cardiocirculatory adaptation (heart rate, blood pressure arm, blood pressure leg) and ventilatory adaptation (VO2, VCO2, fr Vt, VE) were monitored. Blood pressure in the arm, blood concentrations of lactate and ventilatory parameters showed an evolution statistically dependent on the work to which the subject was submitted. Heart rate showed a statistically significant correlation with the ventilatory parameters and work load. The proportional response of the cardioventilatory parameters to the increase in the work load allowed us to evaluate the repercussion of a given exercise and thus avoid exercise of an excessive intensity that could produce cardiocirculatory changes that might entail an added risk. Heart rate presents an excellent correlation, shown in this work, with the oxygen consumption and could therefore be used to quantify the cardiorespiratory and metabolic repercussion of the exercise carried out. Furthermore, this quantification may allow for the adaptation of exercise intensity to the patient thus improving the results obtained from the practice of exercise that has been proven so necessary in these patients.     

Skeletal muscle biochemical adaptations to exercise training in miniature swine

McAllister, Richard M., Brian L. Reiter, John F. Amann, andM. Harold Laughlin. Skeletal muscle biochemical adaptations toexercise training in miniature swine. J. Appl.Physiol. 82(6): 1862-1868, 1997.The primarypurpose of this study was to test the hypothesis that enduranceexercise training induces increased oxidative capacity in porcineskeletal muscle. To test this hypothesis, female miniature swine wereeither trained by treadmill running 5 days/wk over 16-20 wk (Trn;n = 35) or pen confined (Sed;n = 33). Myocardialhypertrophy, lower heart rates during submaximal stages of a maximaltreadmill running test, and increased running time to exhaustion duringthat test were indicative of training efficacy. A variety of skeletalmuscles were sampled and subsequently assayed for the enzymes citratesynthase (CS), 3-hydroxyacyl-CoA dehydrogenase, and lactatedehydrogenase and for antioxidant enzymes. Fiber type composition of arepresentative muscle was also determined histochemically. The largestincrease in CS activity (62%) was found in the gluteus maximus muscle(Sed, 14.7 ± 1.1 µmol · min¹ · g¹;Trn, 23.9 ± 1.0; P < 0.0005).Muscles exhibiting increased CS activity, however, were locatedprimarily in the forelimb; ankle and knee extensor and respiratorymuscles were unchanged with training. Only two muscles exhibited higher3-hydroxyacyl-CoA dehydrogenase activity in Trn compared with Sed.Lactate dehydrogenase activity was unchanged with training, as wereactivities of antioxidant enzymes. Histochemical analysis of thetriceps brachii muscle (long head) revealed lower type IIB fibernumbers in Trn (Sed, 42 ± 6%; Trn, 10 ± 4;P < 0.01) and greater type IID/Xfiber numbers (Sed, 11 ± 2; Trn, 22 ± 3;P < 0.025). These findingsindicate that porcine skeletal muscle adapts to endurance exercisetraining in a manner similar to muscle of humans and other animalmodels, with increased oxidative capacity. Specificmuscles exhibiting these adaptations, however, differ between theminiature swine and other species.

     

Effect of training on cardiovascular response to exercise in women.

Seventeen women (mean age 31 yr) participated in a training program divided into an initial 9-wk period and a subsequent 52-wk period, during which time 6 continued to exercise and the remainder detrained. Improvements in VO2max were significant (+34%) during the initial 9 wk and small (+5%) for the final 52 wk. Four women who stopped training showed a decrease in VO2max (-10%) during the last phase. During the initial 9 wk, central adaptation was important, with SV showing an increase of 28% at 80% VO2max. Peripheral adaptation (a-v O2 difference) was unchanged. Subjects who trained an additional 52 wk showed a slight drop in SV at submaximal work loads from the initial increase following the first 9 wk. When compared with the initial test the change at 9 wk in peripheral adaptation was a small and nonsignificant rise, followed by a significant increase at 61 wk. Women who are very unfit initially (predicted VO2max of 28 ml/kg-min), apparently adapt to the initial training with a central change followed by a much stronger peripheral adaptation during a longer training program.     

Normal adaptations to exercise despite protection against oxidative stress

It has been reported that supplementation with the antioxidant vitamins C and E prevents the adaptive increases in mitochondrial biogenesis and GLUT4 expression induced by endurance exercise. We reevaluated the effects of these antioxidants on the adaptive responses of rat skeletal muscle to swimming in a short-term study consisting of 9 days of vitamins C and E with exercise during the last 3 days and a longer-term study consisting of 8 wk of antioxidant vitamins with exercise during the last 3 wk. The rats in the antioxidant groups were given 750 mg·kg body wt(-1)·day(-1) vitamin C and 150 mg·kg body wt(-1)·day(-1) vitamin E. In rats euthanized immediately after exercise, plasma TBARs were elevated in the control rats but not in the antioxidant-supplemented rats, providing evidence for an antioxidant effect. In rats euthanized 18 h after exercise there were large increases in insulin responsiveness of glucose transport in epitrochlearis muscles mediated by an approximately twofold increase in GLUT4 expression in both the short- and long-term treatment groups. The protein levels of a number of mitochondrial marker enzymes were also increased about twofold. Superoxide dismutases (SOD) 1 and 2 were increased about twofold in triceps muscle after 3 days of exercise, but only SOD2 was increased after 3 wk of exercise. There were no differences in the magnitudes of any of these adaptive responses between the control and antioxidant groups. These results show that very large doses of antioxidant vitamins do not prevent the exercise-induced adaptive responses of muscle mitochondria, GLUT4, and insulin action to exercise and have no effect on the level of these proteins in sedentary rats.     

Training adaptations of baboons to light and moderate treadmill exercise

We evaluated training adaptations by 18 baboons (Papio cynocephalus anubis) to low and moderate quadrupedal walking exercise on a motorized treadmill. Moderate training produced 47% increases in lactate threshold, 63% increases in muscle citrate synthetase activity, increases in percentage of Type IIc muscle fibers, and reduced plasma insulin concentrations. Low training produced only reduced plasma insulin concentrations. Our results indicate that the baboon response to exercise training was similar to that of Homo sapiens, and dependent on exercise intensity.     

Metformin inhibits mitochondrial adaptations to aerobic exercise training in older adults

Metformin and exercise independently improve insulin sensitivity and decrease the risk of diabetes. Metformin was also recently proposed as a potential therapy to slow aging. However, recent evidence indicates that adding metformin to exercise antagonizes the exercise‐induced improvement in insulin sensitivity and cardiorespiratory fitness. The purpose of this study was to test the hypothesis that metformin diminishes the improvement in insulin sensitivity and cardiorespiratory fitness after aerobic exercise training (AET) by inhibiting skeletal muscle mitochondrial respiration and protein synthesis in older adults (62 ± 1 years). In a double‐blinded fashion, participants were randomized to placebo (n = 26) or metformin (n = 27) treatment during 12 weeks of AET. Independent of treatment, AET decreased fat mass, HbA1c, fasting plasma insulin, 24‐hr ambulant mean glucose, and glycemic variability. However, metformin attenuated the increase in whole‐body insulin sensitivity and VO₂max after AET. In the metformin group, there was no overall change in whole‐body insulin sensitivity after AET due to positive and negative responders. Metformin also abrogated the exercise‐mediated increase in skeletal muscle mitochondrial respiration. The change in whole‐body insulin sensitivity was correlated to the change in mitochondrial respiration. Mitochondrial protein synthesis rates assessed during AET were not different between treatments. The influence of metformin on AET‐induced improvements in physiological function was highly variable and associated with the effect of metformin on the mitochondria. These data suggest that prior to prescribing metformin to slow aging, additional studies are needed to understand the mechanisms that elicit positive and negative responses to metformin with and without exercise.