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Showing papers in "Journal of Applied Physiology in 2008"


Journal ArticleDOI
TL;DR: This brief review will summarize age-related changes in aortic and peripheral vascular function and will discuss potential mechanisms leading from changes in properties of large arteries to excessive pressure pulsatility, abnormal microvascular structure and function, and end-organ dysfunction and damage.
Abstract: Over the past decade, numerous studies have shown that increased aortic stiffness is associated with major cardiovascular disease end points, including heart disease, stroke, and kidney disease. Cardiac abnormalities and enhanced atherogenesis in the setting of increased pulsatile load on heart and arteries have been well described. However, recent studies have shown a further association between excessive pressure pulsatility and a number of afflictions of aging that share a predominant microvascular etiology, including many forms of kidney disease and cognitive impairment. In these disorders, microvascular remodeling and impaired regulation of local blood flow, which are related to large artery stiffness and pressure pulsatility, are associated with evidence of diffuse microscopic tissue damage. This brief review will summarize age-related changes in aortic and peripheral vascular function and will discuss potential mechanisms leading from changes in properties of large arteries to excessive pressure pulsatility, abnormal microvascular structure and function, and end-organ dysfunction and damage.

663 citations


Journal ArticleDOI
TL;DR: This mini-review describes and compares methods to assess habitual physical activity in youth and discusses main issues regarding the use and interpretation of data collected with these techniques.
Abstract: Despite much progress with physical activity assessment, the limitations concerning the accurate measurement of physical activity are often amplified in young people due to the cognitive, physiological, and biomechanical changes that occur during natural growth as well as a more intermittent pattern of habitual physical activity in youth compared with adults. This mini-review describes and compares methods to assess habitual physical activity in youth and discusses main issues regarding the use and interpretation of data collected with these techniques. Self-report instruments and movement sensing are currently the most frequently used methods for the assessment of physical activity in epidemiological research; others include heart rate monitoring and multisensor systems. Habitual energy expenditure can be estimated from these input measures with varying degree of uncertainty. Nonlinear modeling techniques, using accelerometry perhaps in combination with physiological parameters like heart rate or temperature, have the greatest potential for increasing the prediction accuracy of habitual physical activity energy expenditure. Although multisensor systems may be more accurate, this must be balanced against feasibility, a balance that shifts with technological and scientific advances and should be considered at the beginning of every new study.

579 citations


Journal ArticleDOI
TL;DR: The best indication that central fatigue is important during submaximal tasks is the disproportionate increase in subjects' perceived effort when maintaining a low target force.
Abstract: Magnetic and electrical stimulation at different levels of the neuraxis show that supraspinal and spinal factors limit force production in maximal isometric efforts ("central fatigue"). In sustained maximal contractions, motoneurons become less responsive to synaptic input and descending drive becomes suboptimal. Exercise-induced activity in group III and IV muscle afferents acts supraspinally to limit motor cortical output but does not alter motor cortical responses to transcranial magnetic stimulation. "Central" and "peripheral" fatigue develop more slowly during submaximal exercise. In sustained submaximal contractions, central fatigue occurs in brief maximal efforts even with a weak ongoing contraction (<15% maximum). The presence of central fatigue when much of the available motor pathway is not engaged suggests that afferent inputs contribute to reduce voluntary activation. Small-diameter muscle afferents are likely to be activated by local activity even in sustained weak contractions. During such contractions, it is difficult to measure central fatigue, which is best demonstrated in maximal efforts. To show central fatigue in submaximal contractions, changes in motor unit firing and force output need to be characterized simultaneously. Increasing central drive recruits new motor units, but the way this occurs is likely to depend on properties of the motoneurons and the inputs they receive in the task. It is unclear whether such factors impair force production for a set level of descending drive and thus represent central fatigue. The best indication that central fatigue is important during submaximal tasks is the disproportionate increase in subjects' perceived effort when maintaining a low target force.

543 citations


Journal ArticleDOI
TL;DR: Overall, very few differences were found in temporal gait parameters or leg kinematics between treadmill and overground walking, which suggests that training individuals with neurological injuries on a treadmill appears to be justified.
Abstract: The goal of this study was to compare treadmill walking with overground walking in healthy subjects with no known gait disorders. Nineteen subjects were tested, where each subject walked on a split-belt instrumented treadmill as well as over a smooth, flat surface. Comparisons between walking conditions were made for temporal gait parameters such as step length and cadence, leg kinematics, joint moments and powers, and muscle activity. Overall, very few differences were found in temporal gait parameters or leg kinematics between treadmill and overground walking. Conversely, sagittal plane joint moments were found to be quite different, where during treadmill walking trials, subjects demonstrated less dorsiflexor moments, less knee extensor moments, and greater hip extensor moments. Joint powers in the sagittal plane were found to be similar at the ankle but quite different at the knee and hip joints. Differences in muscle activity were observed between the two walking modalities, particularly in the tibialis anterior throughout stance, and in the hamstrings, vastus medialis and adductor longus during swing. While differences were observed in muscle activation patterns, joint moments and joint powers between the two walking modalities, the overall patterns in these behaviors were quite similar. From a therapeutic perspective, this suggests that training individuals with neurological injuries on a treadmill appears to be justified.

513 citations


Journal ArticleDOI
TL;DR: Impaired endothelial vascular signaling leading to endothelial dysfunction is one of the earliest vascular changes in the pathogenesis of cardiovascular disease.
Abstract: cardiovascular diseases affect ∼80 million people and are collectively the leading cause of death in the United States ([3][1]). Impaired endothelial vascular signaling leading to endothelial dysfunction is one of the earliest vascular changes in the pathogenesis of cardiovascular disease.

425 citations


Journal ArticleDOI
TL;DR: The theme that emerges from this review is that multiple proinflammatory pathways converge on NF-kappaB in the aged arterial wall, and that the transcriptional activity of NF- kappaB is regulated by multiple nuclear factors during aging, including nuclear enzymes poly(ADP-ribose) polymerase (PARP-1) and SIRT-1.
Abstract: One of the major conceptual advances in our understanding of the pathogenesis of age-associated cardiovascular diseases has been the insight that age-related oxidative stress may promote vascular inflammation even in the absence of traditional risk factors associated with atherogenesis (e.g., hypertension or metabolic diseases). In the present review we summarize recent experimental data suggesting that mitochondrial production of reactive oxygen species, innate immunity, the local TNF-α-converting enzyme (TACE)-TNF-α, and the renin-angiotensin system may underlie NF-κB induction and endothelial activation in aged arteries. The theme that emerges from this review is that multiple proinflammatory pathways converge on NF-κB in the aged arterial wall, and that the transcriptional activity of NF-κB is regulated by multiple nuclear factors during aging, including nuclear enzymes poly(ADP-ribose) polymerase (PARP-1) and SIRT-1. We also discuss the possibility that nucleophosmin (NPM or nuclear phosphoprotein B23), a known modulator of the cellular oxidative stress response, may also regulate NF-κB activity in endothelial cells.

393 citations


Journal ArticleDOI
TL;DR: Myonuclear addition via SC recruitment may be required to achieve substantial myofiber hypertrophy in humans, and individuals with a greater basal presence of SCs demonstrated a remarkable ability to expand the SC pool, incorporate new nuclei, and achieve robust growth.
Abstract: A present debate in muscle biology is whether myonuclear addition is required during skeletal muscle hypertrophy. We utilized K-means cluster analysis to classify 66 humans after 16 wk of knee exte...

387 citations


Journal ArticleDOI
TL;DR: It is demonstrated that upregulation of PGC-1alpha in muscle in vivo is sufficient to greatly improve exercise performance under various exercise paradigms as well as increase peak oxygen uptake.
Abstract: The induction of peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α), a key regulator of mitochondriogenesis, is well-established under multiple physical exercise regimens, includi...

387 citations


Journal ArticleDOI
TL;DR: It is concluded that the acute MPS response after resistance exercise and EAA ingestion is similar between young and old men; however, the response is delayed with aging.
Abstract: Skeletal muscle loss during aging leads to an increased risk of falls, fractures, and eventually loss of independence. Resistance exercise is a useful intervention to prevent sarcopenia; however, t...

382 citations


Journal ArticleDOI
TL;DR: The functional correlates of fatigue observed in both animals and humans during exercise include a decline in peak force, maximal velocity, and peak power, and the extent to which these deleterious functional changes result from direct effects on the myofilaments is facilitated through understanding the molecular mechanisms of the cross-bridge cycle.
Abstract: The functional correlates of fatigue observed in both animals and humans during exercise include a decline in peak force (P0), maximal velocity, and peak power. Establishing the extent to which the...

371 citations


Journal ArticleDOI
TL;DR: Regular physical activity prevents both the age-associated loss of muscle strength and increase in muscle fat infiltration in older adults with moderate functional limitations.
Abstract: Considerable evidence suggests that the loss of strength and muscle mass appear to be inevitable consequences of aging. Moreover, aging is associated with an increase in body fat. This study examin...

Journal ArticleDOI
TL;DR: A short-term, moderate-intensity aerobic exercise intervention improves carotid artery compliance and can restore vascular endothelial function in previously sedentary middle-aged and older adults.
Abstract: Aging affects the function and structure of arteries and increases the risk of cardiovascular diseases (CVD). In healthy sedentary adults, aging is associated with increased stiffness (reduced compliance) of large elastic arteries; impaired vascular endothelial function, including reductions in endothelium-dependent dilation (EDD), release of tissue-type plasminogen activator (fibrinolytic capacity) and endothelial progenitor cell number and function; increased intima-media wall thickness (IMT); and peripheral vasoconstriction (decreased basal leg blood flow). Habitual physical activity/increased aerobic exercise capacity is associated with reduced risk of CVD. Compared with their sedentary peers, adults who regularly perform aerobic exercise demonstrate smaller or no age-associated increases in large elastic artery stiffness, reductions in vascular endothelial function, and increases in femoral artery IMT. A short-term, moderate-intensity aerobic exercise intervention (brisk daily walking for 12 wk) improves carotid artery compliance and can restore vascular endothelial function in previously sedentary middle-aged and older adults. Reduced oxidative stress may be an important mechanism contributing to these effects. Habitual resistance exercise increases (high-intensity) or does not affect (moderate-intensity) large elastic artery stiffness, and prevents/restores the age-associated reduction in basal leg blood flow independent of changes in leg fat-free mass. Habitual exercise favorably modulates several expressions of arterial aging, thus preserving vascular function and possibly reducing the risk of CVD.

Journal ArticleDOI
TL;DR: In this article, the Kety-Schmidt-determined cerebral blood flow (CBF) does not change because the jugular vein is collapsed in the upright position during exercise, however, cerebral oxygenation decreases because of eventual arterial desaturation and marked hyperventilation-related hypocapnia of consequence for CBF.
Abstract: During exercise: the Kety-Schmidt-determined cerebral blood flow (CBF) does not change because the jugular vein is collapsed in the upright position. In contrast, when CBF is evaluated by 133Xe clearance, by flow in the internal carotid artery, or by flow velocity in basal cerebral arteries, a ∼25% increase is detected with a parallel increase in metabolism. During activation, an increase in cerebral O2 supply is required because there is no capillary recruitment within the brain and increased metabolism becomes dependent on an enhanced gradient for oxygen diffusion. During maximal whole body exercise, however, cerebral oxygenation decreases because of eventual arterial desaturation and marked hyperventilation-related hypocapnia of consequence for CBF. Reduced cerebral oxygenation affects recruitment of motor units, and supplemental O2 enhances cerebral oxygenation and work capacity without effects on muscle oxygenation. Also, the work of breathing and the increasing temperature of the brain during exerci...

Journal ArticleDOI
TL;DR: It is concluded that available evidence suggests that exercise signals formation of beneficial endothelial cell phenotype at least in part through changes in SS and wall stretch in the arteries.
Abstract: Current evidence indicates that the ability of physical activity to sustain a normal phenotype of arterial endothelial cells (ECs) plays a central role in the beneficial effects of exercise (Ex) on atherosclerotic disease. Here we evaluate the strength of evidence that shear stress (SS) and/or circumferential wall stress (stretch) are the primary signals, produced by bouts of Ex, that signal altered gene expression in arterial ECs, thereby resulting in a less atherogenic EC phenotype. Current literature indicates that SS is a signal for expression of antiatherogenic genes in cultured ECs, in ECs of isolated arteries, and in ECs of arteries in intact animals. Furthermore, SS levels in the arteries of humans during Ex are in the range that produces beneficial changes. In contrast, complex flow profiles within recirculation zones and/or oscillatory flow patterns can cause proatherogenic gene expression in ECs. In vivo evidence indicates that Ex decreases oscillatory flow/SS in some portions of the arterial tree but may increase oscillatory flow in other areas of the arterial tree. Circumferential wall stress can increase expression of some beneficial EC genes as well, but circumferential wall stress also increases production of reactive oxygen species and increases the expression of adhesion factors and other proatherogenic genes. Interactions of arterial pressure and fluid SS play an important role in arterial vascular health and likely contribute to how Ex bouts signal changes in EC gene expression. It is also clear that other local and circulating factors interact with these hemodynamic signals during Ex to produce the healthy arterial EC phenotype. We conclude that available evidence suggests that exercise signals formation of beneficial endothelial cell phenotype at least in part through changes in SS and wall stretch in the arteries.

Journal ArticleDOI
TL;DR: Single muscle fiber contractile function may be preserved in older humans in the presence of significant alterations at the whole muscle level, which suggests that surviving fibers compensate to partially correct muscle size deficits in an attempt to maintain optimal force-generating capacity.
Abstract: Cross-sectional studies are likely to underestimate age-related changes in skeletal muscle strength and mass. The purpose of this longitudinal study was to assess whole muscle and single muscle fib...

Journal ArticleDOI
TL;DR: It is concluded that participation in 90 days of competitive athletics produces significant training-specific changes in cardiac structure and function and develops biventricular dilation with enhanced diastolic function, while SA develop isolated, concentric left ventricular hypertrophy with diminished diastolics relaxation.
Abstract: This prospective, longitudinal study examined the effects of participation in team-based exercise training on cardiac structure and function. Competitive endurance athletes (EA, n = 40) and strengt...

Journal ArticleDOI
TL;DR: It is concluded that air trapping is a characteristic feature of the severe asthma population, suggesting that there is a pathological process associated with severe asthma that makes airways more vulnerable to this component.
Abstract: Five to ten percent of asthma cases are poorly controlled chronically and refractory to treatment, and these severe cases account for disproportionate asthma-associated morbidity, mortality, and he...

Journal ArticleDOI
TL;DR: While selected markers of training adaptation were enhanced with twice a day training, the performance of a 1-h time trial undertaken after a 60-min steady-state ride was similar after once daily or twice every second day training programs.
Abstract: We determined the effects of a cycle training program in which selected sessions were performed with low muscle glycogen content on training capacity and subsequent endurance performance, whole body substrate oxidation during submaximal exercise, and several mitochondrial enzymes and signaling proteins with putative roles in promoting training adaptation. Seven endurance-trained cyclists/triathletes trained daily (High) alternating between 100-min steady-state aerobic rides (AT) one day, followed by a high-intensity interval training session (HIT; 8 × 5 min at maximum self-selected effort) the next day. Another seven subjects trained twice every second day (Low), first undertaking AT, then 1–2 h later, the HIT. These training schedules were maintained for 3 wk. Forty-eight hours before and after the first and last training sessions, all subjects completed a 60-min steady-state ride (60SS) followed by a 60-min performance trial. Muscle biopsies were taken before and after 60SS, and rates of substrate oxidation were determined throughout this ride. Resting muscle glycogen concentration (412 ± 51 vs. 577 ± 34 μmol/g dry wt), rates of whole body fat oxidation during 60SS (1,261 ± 247 vs. 1,698 ± 174 μmol·kg−1·60 min−1), the maximal activities of citrate synthase (45 ± 2 vs. 54 ± 1 mmol·kg dry wt−1·min−1), and β-hydroxyacyl-CoA-dehydrogenase (18 ± 2 vs. 23 ± 2 mmol·kg dry wt−1·min−1) along with the total protein content of cytochrome c oxidase subunit IV were increased only in Low (all P < 0.05). Mitochondrial DNA content and peroxisome proliferator-activated receptor-γ coactivator-1α protein levels were unchanged in both groups after training. Cycling performance improved by ∼10% in both Low and High. We conclude that compared with training daily, training twice every second day compromised high-intensity training capacity. While selected markers of training adaptation were enhanced with twice a day training, the performance of a 1-h time trial undertaken after a 60-min steady-state ride was similar after once daily or twice every second day training programs.

Journal ArticleDOI
TL;DR: The effects of age, hypertension, and heart failure on E(A)/E(LV) and its components (E(A and E(LV)) in men and women are examined and mechanistic insights that can be derived are highlighted.
Abstract: Understanding the performance of the left ventricle (LV) requires not only examining the properties of the LV itself, but also investigating the modulating effects of the arterial system on left ventricular performance. The interaction of the LV with the arterial system, termed arterial-ventricular coupling (EA/ELV), is a central determinant of cardiovascular performance and cardiac energetics. EA/ELV can be indexed by the ratio of effective arterial elastance (EA; a measure of the net arterial load exerted on the left ventricle) to left ventricular end-systolic elastance (ELV; a load-independent measure of left ventricular chamber performance). At rest, in healthy individuals, EA/ELV is maintained within a narrow range, which allows the cardiovascular system to optimize energetic efficiency at the expense of mechanical efficacy. During exercise, an acute mismatch between the arterial and ventricular systems occurs, due to a disproportionate increase in ELV (from an average of 4.3 to 13.2, and 4.7 to 15.5 mmHg·ml−1·m−2 in men and women, respectively) vs. EA (from an average of 2.3 to 3.2, and 2.3 to 2.9 mmHg·ml−1·m−2 in men and women, respectively), to ensure that sufficient cardiac performance is achieved to meet the increased energetic requirements of the body. As a result EA/ELV decreases from an average of 0.58 to 0.34, and 0.52 to 0.27 in men and women, respectively. In this review, we provide an overview of the concept of EA/ELV, and examine the effects of age, hypertension, and heart failure on EA/ELV and its components (EA and ELV) in men and women. We discuss these effects both at rest and during exercise and highlight the mechanistic insights that can be derived from studying EA/ELV.

Journal ArticleDOI
TL;DR: Mechanisms of importance for hyperthermia-induced fatigue during short intense activities and prolonged exercise in the heat are addressed and the interaction between central and peripheral physiological factors also needs to be considered.
Abstract: The present review addresses mechanisms of importance for hyperthermia-induced fatigue during short intense activities and prolonged exercise in the heat. Inferior performance during physical activities with intensities that elicit maximal oxygen uptake is to a large extent related to perturbation of the cardiovascular function, which eventually reduces arterial oxygen delivery to the exercising muscles. Accordingly, aerobic energy turnover is impaired and anaerobic metabolism provokes peripheral fatigue. In contrast, metabolic disturbances of muscle homeostasis are less important during prolonged exercise in the heat, because increased oxygen extraction compensates for the reduction in systemic blood flow. The decrease in endurance seems to involve changes in the function of the central nervous system (CNS) that lead to fatigue. The CNS fatigue appears to be influenced by neurotransmitter activity of the dopaminergic system, but may primarily relate to inhibitory signals from the hypothalamus arising secondary to an increase in brain temperature. Fatigue is an integrated phenomenon, and psychological factors, including the anticipation of fatigue, should not be neglected and the interaction between central and peripheral physiological factors also needs to be considered.

Journal ArticleDOI
TL;DR: The results indicate that the age-related decline in maximal motor unit discharge frequency likely limit, in addition to the slowing of muscle contractile properties, the performance of fast voluntary contractions.
Abstract: The aim of this study was to investigate the association between the rate of torque development and maximal motor unit discharge frequency in young and elderly adults as they performed rapid submax...

Journal ArticleDOI
TL;DR: Data show that a habitual loading is associated with a significant increase in patellar tendon size and mechanical properties in subjects with a side-to-side strength difference of > or =15% due to sport-induced loading.
Abstract: The purpose of this study was to examine patellar tendon (PT) size and mechanical properties in subjects with a side-to-side strength difference of ≥15% due to sport-induced loading. Seven elite fe...

Journal ArticleDOI
TL;DR: Findings suggest that respiratory muscle fatigue may be involved in limiting exercise tolerance or that other factors, including alterations in the sensation of dyspnea or mechanical load, may be important.
Abstract: It is commonly held that the respiratory system has ample capacity relative to the demand for maximal O2 and CO2 transport in healthy humans exercising near sea level. However, this situation may n...

Journal ArticleDOI
TL;DR: Recent advances in the understanding of the TGF-beta and myostatin signaling pathways are reviewed and the implications of this signaling pathway for skeletal muscle development, physiology, and pathology are focused on.
Abstract: The superfamily of transforming growth factor-beta (TGF-beta) cytokines has been shown to have profound effects on cellular proliferation, differentiation, and growth. Recently, there have been major advances in our understanding of the signaling pathway(s) conveying TGF-beta signals to the nucleus to ultimately control gene expression. One tissue that is potently influenced by TGF-beta superfamily signaling is skeletal muscle. Skeletal muscle ontogeny and postnatal physiology have proven to be exquisitely sensitive to the TGF-beta superfamily cytokine milieu in various animal systems from mice to humans. Recently, major strides have been made in understanding the role of TGF-beta and its closely related family member, myostatin, in these processes. In this overview, we will review recent advances in our understanding of the TGF-beta and myostatin signaling pathways and, in particular, focus on the implications of this signaling pathway for skeletal muscle development, physiology, and pathology.

Journal ArticleDOI
TL;DR: Although it is generally accepted that the promotion of exercise accords with clinical best practice, the anecdotal experience of many primary care physicians, cardiologists, and exercise physiologists is that, even when exercise prescriptions are adhered to, risk factors often fail to demonstrate.
Abstract: although it is generally accepted that the promotion of exercise accords with clinical best practice, the anecdotal experience of many primary care physicians, cardiologists, and exercise physiologists is that, even when exercise prescriptions are adhered to, risk factors often fail to demonstrate

Journal ArticleDOI
TL;DR: The effects of changes in convective O(2) delivery on the development of central and peripheral fatigue are focused on.
Abstract: During exercise, fatigue is defined as a reversible reduction in force- or power-generating capacity and can be elicited by “central” and/or “peripheral” mechanisms. During skeletal muscle contract...

Journal ArticleDOI
TL;DR: During intense contraction some Na(+)-K(+) pumps are inactivated and together with further ionic disturbances, likely precipitate muscle fatigue, and less severe local ionic changes can also augment subtetanic force, suggesting that they may potentiate muscle contractility early in exercise.
Abstract: Membrane excitability is a critical regulatory step in skeletal muscle contraction and is modulated by local ionic concentrations, conductances, ion transporter activities, temperature, and humoral...

Journal ArticleDOI
TL;DR: In general, it appears that both physical activity and CRF are separately and independently associated with metabolic risk factors in youth, possibly through different causal pathways.
Abstract: The metabolic syndrome is defined as the coexistence of multiple cardiovascular and diabetes risk factors, the prevalence of which has increased dramatically in adult populations in the last decades. More recently, the same cluster of metabolic risk factors has also been recognized in children and adolescents. Epidemiological evidence suggests that high levels of cardiorespiratory fitness (CRF) and physical activity are associated with a favorable metabolic risk profile in adults. However, in youth the role of these factors is less clear. Therefore, the purpose of this mini-review is to examine the recent evidence between objectively measured habitual physical activity and CRF with clustered metabolic risk in youth. In general, it appears that both physical activity and CRF are separately and independently associated with metabolic risk factors in youth, possibly through different causal pathways. Further research is necessary to quantify how much physical activity is needed to prevent the metabolic syndrome and the diseases with which it is associated. Public health approaches that encourage increased physical activity and reduce sedentary behaviors may prove useful in reducing the population burden associated with metabolic risk.

Journal ArticleDOI
TL;DR: Progress requires the development of methods that can identify impaired SR Ca(2+) release in intact, blood-perfused muscles and that can distinguish between the various mechanisms proposed.
Abstract: Impaired calcium release from the sarcoplasmic reticulum (SR) has been identified as a contributor to fatigue in isolated skeletal muscle fibers. The functional importance of this phenomenon can be...

Journal ArticleDOI
TL;DR: In this paper, the authors evaluated 12 wk of exercise (aerobic and resistance) or 12wk of weight loss (approximately 7% reduction) on skeletal muscle mRNAs for toll-like receptor-4 (TLR-4), mechanogrowth factor (MGF), TNF-alpha, and IL-6 in 16 obese (body mass index 38+/-2 kg/m2) older (69+/-1 yr) physically frail individuals.
Abstract: Many obese elderly persons have impaired physical function associated with an increased chronic inflammatory response. We evaluated 12 wk of exercise (aerobic and resistance) or 12 wk of weight loss (approximately 7% reduction) on skeletal muscle mRNAs for toll-like receptor-4 (TLR-4), mechanogrowth factor (MGF), TNF-alpha, and IL-6 in 16 obese (body mass index 38+/-2 kg/m2) older (69+/-1 yr) physically frail individuals. Vastus lateralis muscle biopsies were obtained at 0 and 12 wk and analyzed by real-time RT-PCR. Body composition was assessed by dual-energy x-ray absorptiometry. Body weight decreased (-7.5+/-1.2 kg, P=0.001) in the weight loss group but not in the exercise group (-0.3+/-0.8 kg, P=0.74). Fat-free mass (FFM) decreased (-2.9+/-0.6 kg, P=0.010) in the weight loss group and increased (1.6+/-0.6 kg, P=0.03) in the exercise group. Exercise resulted in a 37% decrease in TLR-4 mRNA (P<0.05) while weight loss had no significant effect. Additionally, exercise led to a significant (50%) decrease in IL-6 and TNF-alpha mRNA (P<0.05) while weight loss had no effect. Exercise increased MGF mRNA (approximately 2 fold, P<0.05), but weight loss had no effect. In conclusion, exercise but not weight loss had a beneficial effect on markers of muscle inflammation and anabolism in frail obese elderly individuals.