Chronic aryl hydrocarbon receptor activity impairs muscle mitochondrial function with tobacco smoking.

Background: Accumulating evidence has demonstrated that chronic tobacco smoking directly contributes to skeletal muscle dysfunction independent of its pathological impact to the cardiorespiratory systems. The mechanisms underlying tobacco smoke toxicity in skeletal muscle are not fully resolved. In this study, the role of the aryl hydrocarbon receptor (AHR), a transcription factor known to be activated with tobacco smoke, was investigated.

Muscle fatigue, bioenergetic responses and metabolic economy during load- and velocity-based maximal dynamic contractions in young and older adults.

We evaluated whether task-dependent, age-related differences in muscle fatigue (contraction-induced decline in normalized power) develop from differences in bioenergetics or metabolic economy (ME; mass-normalized work/mM ATP). We used magnetic resonance spectroscopy to quantify intracellular metabolites in vastus lateralis muscle of 10 young and 10 older adults during two maximal-effort, 4-min isotonic (20% maximal torque) and isokinetic (120°s ) contraction protocols. Fatigue, inorganic phosphate (Pi), and pH (p ≥ 0.

Measurements of in vivo skeletal muscle oxidative capacity are lower following sustained isometric compared with dynamic contractions.

Human skeletal muscle oxidative capacity can be quantified non-invasively using 31-phosphorus magnetic resonance spectroscopy (P-MRS) to measure the rate constant of phosphocreatine (PCr) recovery () following contractions. In the quadricep muscles, several studies have quantified following 24-30 s of sustained maximal voluntary isometric contraction (MVIC). This approach has the advantage of simplicity but is potentially problematic because sustained MVICs inhibit perfusion, which may limit muscle oxygen availability or increase the intracellular metabolic perturbation, and thus affect .

The influence of the CYP1A2-163 C>A polymorphism on the hemostatic response to exercise following caffeine supplementation.

Background: Prior work from our group suggests that caffeine increases thrombotic potential after acute exercise. The aim of this study was to determine if hemostatic responses to exercise affected by caffeine are influenced by the CYP1A2-163 C>A polymorphism.

Methods: Forty-two healthy men performed two trials in which a graded maximal exercise test was completed one hour after consuming either 6 mg/kg of caffeine or placebo.

NMR Spectroscopy Identifies Chemicals in Cigarette Smoke Condensate That Impair Skeletal Muscle Mitochondrial Function.

Tobacco smoke-related diseases such as chronic obstructive pulmonary disease (COPD) are associated with high healthcare burden and mortality rates. Many COPD patients were reported to have muscle atrophy and weakness, with several studies suggesting intrinsic muscle mitochondrial impairment as a possible driver of this phenotype. Whereas much information has been learned about muscle pathology once a patient has COPD, little is known about how active tobacco smoking might impact skeletal muscle physiology or mitochondrial health.

Chronic aryl hydrocarbon receptor activity phenocopies smoking-induced skeletal muscle impairment.

Background: Chronic obstructive pulmonary disease (COPD) patients exhibit skeletal muscle atrophy, denervation, and reduced mitochondrial oxidative capacity. Whilst chronic tobacco smoke exposure is implicated in COPD muscle impairment, the mechanisms involved are ambiguous. The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor that activates detoxifying pathways with numerous exogenous ligands, including tobacco smoke.

Effects of old age and contraction mode on knee extensor muscle ATP flux and metabolic economy in vivo.

Key Points: We used 31-phosphorus magnetic resonance spectroscopy to quantify in vivo skeletal muscle metabolic economy (ME; mass-normalized torque or power produced per ATP consumed) during three 24 s maximal-effort contraction protocols: (1) sustained isometric (MVIC), (2) intermittent isokinetic (MVDC ), and (3) intermittent isotonic (MVDC ) in the knee extensor muscles of young and older adults. ME was not different between groups during the MVIC but was lower in older than young adults during both dynamic contraction protocols. These results are consistent with an increased energy cost of locomotion, but not postural support, with age.

Rates of oxidative ATP synthesis are not augmented beyond the pH threshold in human vastus lateralis muscles during a stepwise contraction protocol.

Key Points: The oxygen cost of high-intensity exercise at power outputs above an individual's lactate threshold (LT) is greater than would be predicted by the linear oxygen consumption-power relationship observed below the LT. However, whether these augmentations are caused by an increased ATP cost of force generation (ATP ) or an increased oxygen cost of ATP synthesis is unclear. We used P-MRS to measure changes in cytosolic [ADP] (intramyocellular marker of oxidative metabolism), oxidative ATP synthesis (ATP ) and ATP during a 6-stage, stepwise knee extension protocol.

Muscle architecture, voluntary activation, and low-frequency fatigue do not explain the greater fatigue of older compared with young women during high-velocity contractions.

Although high-velocity contractions elicit greater muscle fatigue in older than young adults, the cause of this difference is unclear. We examined the potential roles of resting muscle architecture and baseline contractile properties, as well as changes in voluntary activation and low-frequency fatigue in response to high-velocity knee extensor work. Vastus lateralis muscle architecture was determined in quiescent muscle by ultrasonography in 8 young (23.

Validity and accuracy of calculating oxidative ATP synthesis in vivo during high-intensity skeletal muscle contractions.

Several methods have been developed for using P-MRS to calculate rates of oxidative ATP synthesis (ATP ) during muscular contractions based on assumptions that (1) the ATP cost of force generation (ATP ) remains constant or (2) Michaelis-Menten coupling between cytosolic ADP and ATP does not change. However, growing evidence suggests that one, or both, of these assumptions are invalid during high-intensity fatigue protocols. Consequently, there is a need to examine the validity and accuracy of traditional ATP calculation methods under these conditions.

Magnetic Resonance Compatible Knee Extension Ergometer.

A magnetic resonance (MR) compatible ergometer has been developed to study contracting lower limb muscles during acquisition of MR spectroscopy data, a technique to noninvasively measure metabolic energy in muscle tissue. Current active and passive MR-compatible ergometer designs lack torque or velocity control to allow precise mechanical measurements during isotonic and isokinetic contractions; incorporating load and velocity controllers while maintaining MR-compatibility is the main challenge. Presented in this paper is the design and evaluation of an MR-compatible ergometer designed to control knee torque or velocity up to 420 N·m and 270 deg/s and is able to operate in a 3 Tesla magnetic field.

Oxidative ATP synthesis in human quadriceps declines during 4 minutes of maximal contractions.

Key Points: During maximal exercise, skeletal muscle metabolism and oxygen consumption remain elevated despite precipitous declines in power. Presently, it is unclear whether these responses are caused by an increased ATP cost of force generation (ATP ) or mitochondrial uncoupling; a process that reduces the efficiency of oxidative ATP synthesis (ATP ). To address this gap, we used 31-phosphorus magnetic resonance spectroscopy to measure changes in ATP and ATP in human quadriceps during repeated trials of maximal intensity knee extensions lasting up to 4 min.

Caffeine Augments the Prothrombotic but Not the Fibrinolytic Response to Exercise.

Unlabelled: Caffeine, a popular ergogenic supplement, induces neural and vascular changes that may influence coagulation and/or fibrinolysis at rest and during exercise.

Purpose: The purpose of this study was to assess the effect of a single dose of caffeine on measures of coagulation and fibrinolysis before and after a single bout of high-intensity exercise.

Methods: Forty-eight men (age, 23 ± 3 yr; body mass index, 24 ± 3 kg·m) completed two trials, with 6 mg·kg of caffeine (CAFF) or placebo (PLAC), in random order, followed by a maximal cycle ergometer test.

In vivo mitochondrial function in aging skeletal muscle: capacity, flux, and patterns of use.

Because of the fundamental dependence of mammalian life on adequate mitochondrial function, the question of how and why mitochondria change in old age is the target of intense study. Given the importance of skeletal muscle for the support of mobility and health, this question extends to the need to understand mitochondrial changes in the muscle of older adults, as well. We and others have focused on clarifying the age-related changes in human skeletal muscle mitochondrial function in vivo.

Heterogeneous effects of old age on human muscle oxidative capacity in vivo: a systematic review and meta-analysis.

Despite intensive efforts to understand the extent to which skeletal muscle mitochondrial capacity changes in older humans, the answer to this important question remains unclear. To determine what the preponderance of evidence from in vivo studies suggests, we conducted a systematic review and meta-analysis of the effects of age on muscle oxidative capacity as measured noninvasively by magnetic resonance spectroscopy. A secondary aim was to examine potential moderators contributing to differences in results across studies, including muscle group, physical activity status, and sex.