[Physical activity and chronic disease I. Heart disease and hypertension].
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Chronic Disease↗
Biomedical subjects
Michael Kjaer
Publications and source records attributed to Michael Kjaer.
[Physical activity and chronic disease II. Type 2 diabetes, obesity and cancer].
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Chronic Disease↗
[Physical activity and chronic disease III. Musculoskeletal diseases and lung diseases].
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Asthma↗
Enhanced procollagen processing in skeletal muscle after a single bout of eccentric loading in humans.
Increases in procollagen processing within skeletal muscle have previously been reported in small animal models only. While indirect measurements in humans have suggested an increase procollagen processing, no intra-skeletal muscle measurements have confirmed these findings. In this study, eight young healthy male subjects performed a single bout of unaccustomed high intensity eccentric exercise on one leg, with the contralateral leg being the control. A significant increase in the muscle interstitial concentration of the N-terminal propeptide of procollagen type I (PINP) was observed (day 0: 1.96 +/- 0.44 ng ml(-1), day 2: 1.94 +/- 0.32 ng ml(-1), day 4: 3.90 +/- 1.03 ng ml(-1), day 8: 7.23 +/- 2.34 ng ml(-1)*, *P < 0.05 vs. basal and control) with no change being noted in the control leg. By day 2 post-exercise, an increase in the histological immunoreactivity of PINP and the N-terminal propeptide of procollagen type III (PIIINP) was also shown in the exercising leg only. Further, from day 2 post-exercise, immunoreactivity for tenascin C and reactive macrophages (CD68+ cells) was seen within the perimysial and endomysial connective tissue of the exercising leg only, indicating a high mechanical load and inflammation. This study shows that following a single bout of high intensity eccentric exercise there is an increase in procollagen processing within skeletal muscle in humans.
Adult↗
Resistance training in the early postoperative phase reduces hospitalization and leads to muscle hypertrophy in elderly hip surgery patients--a controlled, randomized study.
OBJECTIVES: To better understand how immobilization and surgery affect muscle size and function in the elderly and to identify effective training regimes. DESIGN: A prospective randomized, controlled study. SETTING: Bispebjerg University Hospital, Copenhagen, Denmark. PARTICIPANTS: Thirty-six patients (aged 60-86) scheduled for unilateral hip replacement due to primary hip osteoarthrosis. INTERVENTION: Patients were randomized to standard home-based rehabilitation (1 h/d x 12 weeks), unilateral neuromuscular electrical stimulation of the operated side (1 h/d x 12 weeks), or unilateral resistance training of the operated side (3/wk x 12 weeks). MEASUREMENTS: Hospital length of stay (LOS), quadriceps muscle cross-sectional area (CSA), isokinetic muscle strength, and functional performance. Patients were tested presurgery and 5 and 12 weeks postsurgery. RESULTS: Mean+/-standard error LOS was shorter for the resistance training group (10.0+/-2.4 days, P<.05) than for the standard rehabilitation group (16.0+/-7.2 days). Resistance training, but not electrical stimulation or standard rehabilitation, resulted in increased CSA (12%, P<.05) and muscle strength (22-28%, P<.05). Functional muscle performance increased after resistance training (30%, P<.001) and electrical stimulation (15%, P<.05) but not after standard rehabilitation. CONCLUSION: Postoperative resistance training effectively increased maximal muscle strength, muscle mass, and muscle function more than a standard rehabilitation regime. Furthermore, it markedly reduced LOS in elderly postoperative patients.
Activities of Daily Living↗
Role of extracellular matrix in adaptation of tendon and skeletal muscle to mechanical loading.
The extracellular matrix (ECM), and especially the connective tissue with its collagen, links tissues of the body together and plays an important role in the force transmission and tissue structure maintenance especially in tendons, ligaments, bone, and muscle. The ECM turnover is influenced by physical activity, and both collagen synthesis and degrading metalloprotease enzymes increase with mechanical loading. Both transcription and posttranslational modifications, as well as local and systemic release of growth factors, are enhanced following exercise. For tendons, metabolic activity, circulatory responses, and collagen turnover are demonstrated to be more pronounced in humans than hitherto thought. Conversely, inactivity markedly decreases collagen turnover in both tendon and muscle. Chronic loading in the form of physical training leads both to increased collagen turnover as well as, dependent on the type of collagen in question, some degree of net collagen synthesis. These changes will modify the mechanical properties and the viscoelastic characteristics of the tissue, decrease its stress, and likely make it more load resistant. Cross-linking in connective tissue involves an intimate, enzymatical interplay between collagen synthesis and ECM proteoglycan components during growth and maturation and influences the collagen-derived functional properties of the tissue. With aging, glycation contributes to additional cross-linking which modifies tissue stiffness. Physiological signaling pathways from mechanical loading to changes in ECM most likely involve feedback signaling that results in rapid alterations in the mechanical properties of the ECM. In developing skeletal muscle, an important interplay between muscle cells and the ECM is present, and some evidence from adult human muscle suggests common signaling pathways to stimulate contractile and ECM components. Unaccostumed overloading responses suggest an important role of ECM in the adaptation of myofibrillar structures in adult muscle. Development of overuse injury in tendons involve morphological and biochemical changes including altered collagen typing and fibril size, hypervascularization zones, accumulation of nociceptive substances, and impaired collagen degradation activity. Counteracting these phenomena requires adjusted loading rather than absence of loading in the form of immobilization. Full understanding of these physiological processes will provide the physiological basis for understanding of tissue overloading and injury seen in both tendons and muscle with repetitive work and leisure time physical activity.
Animals↗
Influence of age and resistance exercise on human skeletal muscle proteolysis: a microdialysis approach.
We combined the interstitial sampling method of microdialysis with the natural tracer qualities (i.e. non-recyclability) of the amino acid 3-methylhistidine (3MH) to uniquely study in vivo degradation of the two most abundant skeletal muscle proteins, myosin and actin. Interstitial 3MH concentration was measured before and for 24 h following a single bout of resistance exercise in eight young (27 +/- 2 years) and eight old (75 +/- 4 years) men. The exercise bout consisted of four exercises (3 sets of 8 repetitions at 80% one-repetition maximum (1RM) per exercise) emphasizing the quadriceps. Interstitial 3MH concentration was calculated using the internal reference method from microdialysate samples that were obtained from two microdialysis probes placed in the vastus lateralis. Resting interstitial 3MH concentration was 44% higher (P < 0.05) in the old (6.16 +/- 0.56 nmol ml(-1)) as compared with the young (4.28 +/- 0.27 nmol ml(-1)). Interstitial 3MH was not different (P > 0.05) from preexercise at any time point within the 24 h following exercise in both the young and the old. Leg arteriovenous exchange measurements in a separate group of young subjects also showed no increase in 3MH release during the 4 h following a resistance exercise bout compared with a non-exercised control leg (control leg: -28 +/- 6, exercise leg: -28 +/- 11 nmol min(-1)). These results suggest that myosin and actin proteolysis are not increased in the first 24 h following a standard bout of resistance exercise, and this response is not altered with ageing. The higher interstitial 3MH concentration in the old suggests an increased proteolysis of the two main contractile proteins in the rested and fasted state, which is consistent with a decrease in muscle mass with ageing. Microdialysis is an appropriate methodology for use in ageing individuals and is compatible with high-intensity resistance exercise.
Actins↗
Role of TGF-beta1 in relation to exercise-induced type I collagen synthesis in human tendinous tissue.
Mechanical loading of tissue is known to influence local collagen synthesis, and microdialysis studies indicate that mechanical loading of human tendon during exercise elevates tendinous type I collagen production. Transforming growth factor-beta1 (TGF-beta1), a potent stimulator of type I collagen synthesis, is released from cultured tendon fibroblasts in response to mechanical loading. Thus TGF-beta1 could link mechanical loading and collagen synthesis in tendon tissue in vivo. Tissue levels of TGF-beta1 and type I collagen metabolism markers [procollagen I COOH-terminal propeptide (PICP) and COOH-terminal telopeptide of type I collagen (ICTP)] were measured by microdialysis in peritendinous tissue of the Achilles' tendon in six male volunteers before and after treadmill running (1 h, 12 km/h, 3% uphill). In addition, blood levels of TGF-beta1, PICP, and ICTP were obtained. PICP levels increased 68 h after exercise (P < 0.05). Dialysate levels of TGF-beta1 changed from 303 +/- 46 pg/ml (at rest) to 423 +/- 86 pg/ml 3 h postexercise. This change was nonsignificant, but the decay of tissue TGF-beta1 after catheter insertion was markedly delayed by exercise compared with the decay seen in resting subjects. Plasma concentrations of TGF-beta1 rose 30% in response to exercise (P < 0.05 vs. pre). Our observations indicate an increased local production of type I collagen in human peritendinous tissue in response to uphill running. Although not conclusive, changes in circulating and local TGF-beta1, in response to exercise, suggest a role for TGF-beta1 in mechanical regulation of local collagen type I synthesis in tendon-related connective tissue in vivo.
Achilles Tendon↗
Region-specific differences in Achilles tendon cross-sectional area in runners and non-runners.
The present study examined the cross-sectional area (CSA) of the Achilles tendon in subjects who repeatedly exposed their tendons to large loads (habitual runners) compared to control subjects (non-runners). Six male habitual runners [36 (7) years, 70.9 (4.4) kg and 1.84 (0.05) m, +/-SD] who had performed distance running (approximately 80 km per week) for the last 5 years were compared to six non-runners [34 (3) years, 81.2 (8.7) kg and 1.81 (0.02) m, +/-SD]. Tendon CSA was obtained from MR images obtained with the ankle in a neutral position (90 degrees ). The most proximal aspect of the tuberosity of calcaneus was used as a landmark to standardize the levels of images: the most distal image (1) was obtained 10 mm above the proximal tuberosity of calcaneus, and the most proximal image (7) was obtained 70 mm above the proximal tuberosity of calcaneus. There was a significant difference in CSA along the length of the tendon both in runners ( P<0.001) and non-runners ( P<0.01). In non-runners and runners the CSA of the most distal part was 51% and 85% greater than the most proximal part of the tendon, respectively. Furthermore, there was a difference in tendon CSA between the groups, such that runners had a greater CSA (36%) than non-runners at the most distal part of the tendon ( P<0.05). The greater CSA in the distal tendon may reflect differences in structural properties along the length of the human Achilles tendon, while the greater CSA in runners compared to non-runners may indicate a region-specific hypertrophy in response to the habitual loading of running.
Achilles Tendon↗
Exercise-induced changes in circulating levels of transforming growth factor-beta-1 in humans: methodological considerations.
Mechanical loading of cells induces the expression of transforming growth factor-beta-1, and acute exercise, which involves mechanical loading of several tissues, could thus increase its circulating level in humans. However, no consensus exists regarding the plasma concentration of this cytokine in resting subjects (reported values range from 500 to 18,300 pg ml(-1)) and also the extent of intra-individual variation is unknown. As a basis for detecting exercise-induced changes in transforming growth factor-beta-1, we measured its concentration, by enzyme-linked immunosorbent assay, in plasma from eight healthy resting subjects. Plasma was sampled from each subject on five successive days according to a procedure designed to minimize activation of platelets, as platelet alpha-granules contain large amounts of transforming growth factor-beta-1. The mean plasma level was relatively low [1155 (30) pg ml(-1), mean (SE)], and did not differ between days, indicating that platelet activation was minimal. Several alterations in the blood sampling procedure did not affect results, while a 40% increase was seen when blood was not cooled appropriately prior to centrifugation. A moderate intra-individual variation (average CV=9.8%) indicated a stable plasma level at rest. In response to exercise (1 h of treadmill running) the plasma concentration of transforming growth factor-beta-1 increased from 992 (49) pg ml(-1) (at rest) to 1301 (39) pg ml(-1) (post exercise) ( P<0.05) ( n=6). In conclusion, the resting plasma level of transforming growth factor-beta-1 was stable over time when blood samples were treated appropriately. Exercise increased the plasma concentration, perhaps indicating a release from mechanically loaded tissues.
Adult↗
Cardiovascular control during exercise: insights from spinal cord-injured humans.
BACKGROUND: We studied the role of the central nervous system, neural feedback from contracting skeletal muscles, and sympathetic activity to the heart in the control of heart rate and blood pressure during 2 levels of dynamic exercise. METHODS AND RESULTS: Spinal cord-injured individuals (SCI) with (paraplegia, n=4) or without (tetraplegia, n=6) sympathetic innervation to the heart performed electrically induced exercise. Responses were compared with those established by able-bodied individuals (control, n=6) performing voluntary exercise at a similar pulmonary oxygen uptake. In all subjects, cardiac output and leg blood flow increased, but in SCI they reached a maximal value. The increase in cardiac output was mainly elicited by an increase in stroke volume in individuals with tetraplegia, whereas in individuals with paraplegia it was by heart rate. The increase in SCI was slow compared with that in controls. During exercise, blood pressure was stable in controls, whereas it decreased over time in SCI and especially in individuals with tetraplegia. CONCLUSIONS: The autonomic nervous system provides for acceleration of the heart at the onset of exercise, but a slow increase in heart rate is established even without central command, neural feedback from working muscles, or autonomic influence on the heart. Yet an intact autonomic nervous system is a prerequisite for a large rise in cardiac output and in turn leg blood flow during exercise. Thus, when the sympathetic nervous system is injured at a level where it influences the heart, vasodilatation in working muscles challenges blood pressure.
Blood Pressure↗
[Overuse injuries in tendon tissue: insight into adaptation mechanisms].
Tendon tissue plays a central role in force transmission from skeletal muscles to bones and is subject to a considerable amount of overuse injuries associated with occupation and leisure exercise. It has been shown that connective tissue within and around tendon displays increased blood flow and metabolic activity during exercise in vivo and that the extracellular matrix is stimulated by physical activity whereby both collagen synthesis and degradation are enhanced in both tendon and muscle. Training leads to a net synthesis of collagen type I in tendon, and the thicker tendons that well-trained individuals possess contribute to a lower relative loading of the tendons during exercise. Signals for increased collagen synthesis seem to run in parallel with mechanically induced activation of protease driven degradation of connective tissue in tendon and muscle. Hormonal growth factors as well as inflammatory mediators play a role for this effect, but the relative importance of individual factors in the development of acute or chronic tendon injuries in relation to sports remains uncertain. Newly developed in-vivo techniques open new possibilities for a deeper understanding of the pathogenesis behind tendon overuse injuries.
Adaptation, Physiological↗
ATP and heat production in human skeletal muscle during dynamic exercise: higher efficiency of anaerobic than aerobic ATP resynthesis.
The aim of the present study was to simultaneously examine skeletal muscle heat production and ATP turnover in humans during dynamic exercise with marked differences in aerobic metabolism. This was done to test the hypothesis that efficiency is higher in anaerobic than aerobic ATP resynthesis. Six healthy male subjects performed 90 s of low intensity knee-extensor exercise with (OCC) and without thigh occlusion (CON-LI) as well as 90 s of high intensity exercise (CON-HI) that continued from the CON-LI bout. Muscle heat production was determined by continuous measurements of muscle heat accumulation and heat release to the blood. Muscle ATP production was quantified by repeated measurements of thigh oxygen uptake as well as blood and muscle metabolite changes. All temperatures of the thigh were equalized to approximately 37 degrees C prior to exercise by a water-perfused heating cuff. Oxygen uptake accounted for 80 +/- 2 and 59 +/- 4 %, respectively, of the total ATP resynthesis in CON-LI and CON-HI, whereas it was negligible in OCC. The rise in muscle temperature was lower (P < 0.05) in OCC than CON-LI (0.32 +/- 0.04 vs. 0.37 +/- 0.03 degrees C). The mean rate of heat production was also lower (P < 0.05) in OCC than CON-LI (36 +/- 4 vs. 57 +/- 4 J s-1). Mechanical efficiency was 52 +/- 4 % after 15 s of OCC and remained constant, whereas it decreased (P < 0.05) from 56 +/- 5 to 32 +/- 3 % during CON-LI. During CON-HI, mechanical efficiency transiently increased (P < 0.05) to 47 +/- 4 %, after which it decreased (P < 0.05) to 36 +/- 3 % at the end of CON-HI. Assuming a fully coupled mitochondrial respiration, the ATP turnover per unit of work was calculated to be unaltered during OCC (approximately 20 mmol ATP kJ-1), whereas it increased (P < 0.05) from 21 +/- 4 to 29 +/- 3 mmol ATP kJ-1 during CON-LI and further (P < 0.05) to 37 +/- 3 mmol ATP kJ-1 during CON-HI. The present data confirm the hypothesis that heat loss is lower in anaerobic ATP resynthesis than in oxidative phosphorylation and can in part explain the finding that efficiency declines markedly during dynamic exercise. In addition, the rate of ATP turnover apparently increases during constant load low intensity exercise. Alternatively, mitochondrial efficiency is lowered as exercise progresses, since ATP turnover was unaltered during the ischaemic exercise bout.
Adenosine Triphosphate↗
Human skeletal muscle mitochondrial metabolism in youth and senescence: no signs of functional changes in ATP formation and mitochondrial oxidative capacity.
The mitochondrial theory of ageing was tested. Isolated mitochondria from the quadriceps muscle from normal, healthy, young (age 20+ years, n=12) and elderly (70+ years, n=11) humans were studied in respiratory experiments and the data expressed as activities of the muscle. In each group, the subjects exhibited a variation of physical activity but, on average, the groups were representative for their age with maximum O(2) consumption rate of 50+/-9 and 34+/-13 ml min(-1) kg(-1) (mean+/-SD), respectively. Thirteen different activities were assayed. alpha-Glycerophosphate oxidation was lower in the 70+ group (38%, P~0.001), as was the respiratory capacity for fatty acids (19%, P~0.03). The remaining eleven activities, including those of the central bioenergetic reactions, were not lower in the 70+ group. Pyruvate and alpha-ketoglutarate dehydrogenase activities (i.e. the tricarboxylic acid cycle turnover) and the respiratory chain activity could all account for ~14 mmol O(2) min(-1) kg(-1) muscle (37 degrees C). The capacity for aerobic ATP synthesis was ~35 mmol ATP min(-1) kg(-1). The mitochondrial capacities were far in excess of whole-body performance. They were related to physical activity, but not to age. The mitochondrial theory of ageing, which attributes the age-related decline of muscle performance to decreased mitochondrial function, is incompatible with these results.
Adenosine Triphosphate↗
Effect of training on contractile and metabolic properties of wrist extensors in spinal cord-injured individuals.
Paretic human muscle rapidly loses strength and oxidative endurance, and electrical stimulation training may partly reverse this. We evaluated the effects of two training protocols on the contractile and metabolic properties of the wrist extensor in 12 C-5/6 tetraplegic individuals. The wrist extensor muscles were stimulated for 30 min/day, 5 days/week, for 12 weeks, using either a high-resistance (Hr) or a low-resistance (Lr) protocol. Total work output was similar in both protocols. The nontrained arm was used as a control. Maximum voluntary torque increased in the Hr (P < 0.05) but not the Lr group. Electrically stimulated peak tetanic torque at 15 HZ, 30 HZ, and 50 HZ were unchanged in the Lr group and tended to increase only at 15 HZ (P < 0.1) in the Hr group. Resistance to fatigue, however, increased (P < 0.05) in both Hr (42%) and Lr (41%) groups. Muscle metabolism was evaluated by (31)P nuclear magnetic resonance spectroscopy ((31)P-NMRS) during and following a continuous 40-s 10-HZ contraction. In the Hr group the cost of contraction decreased by 38% (P < 0.05) and the half-time of phosphocreatine (PCr) recovery was shortened by 52% (P < 0.05). Thus, long-term electrically induced stimulation of the wrist extensor muscles in spinal cord injury (SCI) increases fatigue resistance independent of training pattern. However, only the Hr protocol increased muscle strength and was shown to improve muscle aerobic metabolism after training. Muscle Nerve 27: 72-80, 2003
Adult↗
Experimental evidence against the mitochondrial theory of aging. A study of isolated human skeletal muscle mitochondria.
The mitochondrial theory of aging was tested with optimised preparation techniques. Mitochondria were isolated from approximately 90 mg quadriceps muscle from healthy humans at age 70+ and 20+. The content of mitochondrial protein was approximately 10 mg g(-1) muscle and the yields were approximately 40%. The mitochondrial integrity was high as judged from the respiratory control and P/O ratios. No general membrane alterations or changes in the cytochrome contents were observed. BSA decreased the non-phosphorylating rates of respiration equally in both age groups. Thirteen different enzyme activities were assayed and normalised to protein content and citrate synthase activity. Most of the critical levels for detection of declines were <10%. In the 70+ group, the activity for fatty acid oxidation was decreased by approximately 20%. Two inherently low activities associated with oxidation of sarcoplasmic NADH were also decreased, probably related to the age change of fibre types. The remaining activities measured, e.g. those of pyruvate dehydrogenase, tricarboxylic acid cycle, respiratory chain, and ATP synthesis, were not observed to be lowered. Thus, the central bioenergetic systems appeared unaltered with age. The obvious discord with reported age declines of human skeletal muscle mitochondrial function is discussed. It is concluded that the present results are incompatible with the mitochondrial theory of aging.
Adult↗
Increased cross-sectional area and reduced tensile stress of the Achilles tendon in elderly compared with young women.
The Achilles tendon cross-sectional area (CSA), tensile force, and stress during an isometric contraction were examined in healthy young (n = 9, age = 29 +/- 1 years, mean +/- SEM) and elderly (n = 10, 79 +/- 2 years) women. CSA area was obtained with magnetic resonance imaging 3 cm proximal to the insertion, and tendon force was obtained from the isometric ankle moment. The moment of force about the ankle joint was greater in young women (95 +/- 17 N m) than in elderly women (51 +/- 5 N m; p <.05). The Achilles tendon CSA was significantly greater in elderly women (56.3 +/- 3.0 mm(2)) than in young women (46.0 +/- 1.9 mm(2); p <.01). These data show that young women can exert a greater force than elderly women on the Achilles tendon during voluntary contraction, although elderly women have an increased (22%) tendon CSA, and a lower tendon force than young women. The greater tendon size combines to lower the stress on the tendon markedly, which may reduce the risk of injury to the tendon.
Achilles Tendon↗
Incidence of injury and physical performance adaptations during military training.
OBJECTIVE: Strenuous physical activity, such as military training, is known to demand a high degree of physical performance and to cause overuse injuries. However, the exact relation between injury incidence and physical fitness level and the influence of military training on measures of functional performance, such as intermittent endurance capacity and maximal jump performance, are not fully described. METHODS: A total of 330 military conscripts were prospectively followed during military basic training. They were divided into 4 self-assessed physical fitness level groups (well trained, trained, less trained, and untrained) and underwent physical performance tests together with registration of injury incidence. RESULTS: Twelve weeks of military basic training was found to result in an overall injury rate of 28%, with an inverse relation between physical fitness level and incidence of overuse injury (P < 0.0001). Furthermore a fourfold higher injury rate was observed in the previously untrained soldiers compared with the well-trained soldiers. An increase in intermittent endurance capacity (20-m intermittent shuttle run test) was seen in all groups, (13 to 62%, P < 0.05), whereas only the previously untrained group of soldiers improved in aerobic capacity (8 and 16%, P < 0.05; maximal oxygen uptake and Coopers 12-minute running test). Maximal jump performance, both with and without backpack loading (15 kg), decreased (5 to 13%, P < 0.05) in 93% of the soldiers despite weight loss. CONCLUSIONS: Military basic training has a positive effect on intermittent endurance capacity but a detrimental effect on jump performance. Furthermore, low levels of physical fitness are strongly associated with proneness toward overuse injury development in soldiers going through intense training.
Adaptation, Physiological↗