Ryan Godsk Larsen

Effects of old age on human skeletal muscle energetics during fatiguing contractions with and without blood flow

We recently reported lower glycolytic flux (ATPGLY) and increased reliance on oxidative ATP synthesis (ATPOX) in contracting muscle of older compared to young humans. To further investigate this age‐related difference in the pathways of ATP synthesis, we used magnetic resonance spectroscopy to determine the rates of ATPOX, ATPGLY and net phosphocreatine hydrolysis in vivo during maximal muscle contractions under free‐flow (FF) and ischaemic (ISC) conditions in the ankle dorsiflexors of 20 young (27 ± 3 years; 10 male, 10 female) and 18 older (70 ± 5 years; 10 male, 8 female) adults. We hypothesized that ATPGLY would be higher in young compared to old during FF contractions, but that old would be unable to increase ATPGLY during ISC to match that of the young, which would suggest impaired glycolytic ATP synthesis with old age. Peak glycolytic flux during FF was lower in older (0.8 ± 0.1 mm ATP s−1) compared to young (1.4 ± 0.1 mm ATP s−1, P < 0.001) subjects. During ISC, peak ATPGLY increased in old to a level similar to that of young (1.4 ± 0.2 mm ATP s−1, 1.3 ± 0.2 mm ATP s−1, respectively; P= 0.86), suggesting that glycolytic function remains intact in aged muscle in vivo. Notably, older adults fatigued less than young during both FF and ISC (P≤ 0.004). These results provide novel evidence of unimpaired in vivo glycolytic function in the skeletal muscle of older adults during maximal isometric dorsiflexion, and suggest a potential role for differences in metabolic economy and as a result, metabolite accumulation, in the fatigue resistance of the old.

Age-related changes in oxidative capacity differ between locomotory muscles and are associated with physical activity behavior.

There is discrepancy in the literature regarding the degree to which old age affects muscle bioenergetics. These discrepancies are likely influenced by several factors, including variations in physical activity (PA) and differences in the muscle group investigated. To test the hypothesis that age may affect muscles differently, we quantified oxidative capacity of tibialis anterior (TA) and vastus lateralis (VL) muscles in healthy, relatively sedentary younger (8 YW, 8 YM; 21-35 years) and older (8 OW, 8 OM; 65-80 years) adults. To investigate the effect of physical activity on muscle oxidative capacity in older adults, we compared older sedentary women to older women with mild-to-moderate mobility impairment and lower physical activity (OIW, n = 7), and older sedentary men with older active male runners (OAM, n = 6). Oxidative capacity was measured in vivo as the rate constant, k(PCr), of postcontraction phosphocreatine recovery, obtained by (31)P magnetic resonance spectroscopy following maximal isometric contractions. While k(PCr) was higher in TA of older than activity-matched younger adults (28%; p = 0.03), older adults had lower k(PCr) in VL (23%; p = 0.04). In OIW compared with OW, k(PCr) was lower in VL (∼45%; p = 0.01), but not different in TA. In contrast, OAM had higher k(PCr) than OM (p = 0.03) in both TA (41%) and VL (54%). In older adults, moderate-to-vigorous PA was positively associated with k(PCr) in VL (r = 0.65, p < 0.001) and TA (r = 0.41, p = 0.03). Collectively, these results indicate that age-related changes in oxidative capacity vary markedly between locomotory muscles, and that altered PA behavior may play a role in these changes.

In vivo oxidative capacity varies with muscle and training status in young adults

It is well established that exercise training results in increased muscle oxidative capacity. Less is known about how oxidative capacities in distinct muscles, in the same individual, are affected by different levels of physical activity. We hypothesized that 1) trained individuals would have higher oxidative capacity than untrained individuals in both tibialis anterior (TA) and vastus lateralis (VL) and 2) oxidative capacity would be higher in TA than VL in untrained, but not in trained, individuals. Phosphorus magnetic resonance spectroscopy was used to measure the rate of phosphocreatine recovery (k(PCr)), which reflects the rate of oxidative phosphorylation, following a maximal voluntary isometric contraction of the TA and VL in healthy untrained (7 women, 7 men, 25.7 +/- 3.6 yr; mean +/- SD) and trained (5 women, 7 men, 27.5 +/- 3.4 yr) adults. Daily physical activity levels were measured using accelerometry. The trained group spent threefold more time ( approximately 90 vs. approximately 30 min/day; P < 0.001) in moderate to vigorous physical activity (MVPA). Overall, k(PCr) was higher in VL than in TA (P = 0.01) and higher in trained than in untrained participants (P < 0.001). The relationship between k(PCr) and MVPA was more robust in VL (r = 0.64, P = 0.001, n = 25) than in TA (r = 0.38, P = 0.06, n = 25). These results indicate greater oxidative capacity in vivo in trained compared with untrained individuals in two distinct muscles of the lower limb and provide novel evidence of higher oxidative capacity in VL compared with TA in young humans, irrespective of training status. The basis for this difference is not known at this time but likely reflects a difference in usage patterns between the muscles.

High-intensity interval training increases in vivo oxidative capacity with no effect on Pi→ATP rate in resting human muscle

Mitochondrial ATP production is vital for meeting cellular energy demand at rest and during periods of high ATP turnover. We hypothesized that high-intensity interval training (HIT) would increase ATP flux in resting muscle (VPi→ATP) in response to a single bout of exercise, whereas changes in the capacity for oxidative ATP production (Vmax) would require repeated bouts. Eight untrained men (27 ± 4 yr; peak oxygen uptake = 36 ± 4 ml·kg(-1)·min(-1)) performed six sessions of HIT (4-6 × 30-s bouts of all-out cycling with 4-min recovery). After standardized meals and a 10-h fast, VPi→ATP and Vmax of the vastus lateralis muscle were measured using phosphorus magnetic resonance spectroscopy at 4 Tesla. Measurements were obtained at baseline, 15 h after the first training session, and 15 h after completion of the sixth session. VPi→ATP was determined from the unidirectional flux between Pi and ATP, using the saturation transfer technique. The rate of phosphocreatine recovery (kPCr) following a maximal contraction was used to calculate Vmax. While kPCr and Vmax were unchanged after a single session of HIT, completion of six training sessions resulted in a ∼14% increase in muscle oxidative capacity (P ≤ 0.004). In contrast, neither a single nor six training sessions altered VPi→ATP (P = 0.74). This novel analysis of resting and maximal high-energy phosphate kinetics in vivo in response to HIT provides evidence that distinct aspects of human skeletal muscle metabolism respond differently to this type of training.

Human skeletal muscle metabolic economy in vivo: effects of contraction intensity, age, and mobility impairment

We tested the hypothesis that older muscle has greater metabolic economy (ME) in vivo than young, in a manner dependent, in part, on contraction intensity. Twenty young (Y; 24±1 yr, 10 women), 18 older healthy (O; 73±2, 9 women) and 9 older individuals with mild-to-moderate mobility impairment (OI; 74±1, 7 women) received stimulated twitches (2 Hz, 3 min) and performed nonfatiguing voluntary (20, 50, and 100% maximal; 12 s each) isometric dorsiflexion contractions. Torque-time integrals (TTI; Nm·s) were calculated and expressed relative to maximal fat-free muscle cross-sectional area (cm2), and torque variability during voluntary contractions was calculated as the coefficient of variation. Total ATP cost of contraction (mM) was determined from flux through the creatine kinase reaction, nonoxidative glycolysis and oxidative phosphorylation, and used to calculate ME (Nm·s·cm(-2)·mM ATP(-1)). While twitch torque relaxation was slower in O and OI compared with Y (P≤0.001), twitch TTI, ATP cost, and economy were similar across groups (P≥0.15), indicating comparable intrinsic muscle economy during electrically induced isometric contractions in vivo. During voluntary contractions, normalized TTI and total ATP cost did not differ significantly across groups (P≥0.20). However, ME was lower in OI than Y or O at 20% and 50% MVC (P≤0.02), and torque variability was greater in OI than Y or O at 20% MVC (P≤0.05). These results refute the hypothesis of greater muscle ME in old age, and provide support for lower ME in impaired older adults as a potential mechanism or consequence of age-related reductions in functional mobility.

High-intensity interval training alters ATP pathway flux during maximal muscle contractions in humans

High‐intensity interval training (HIT) results in potent metabolic adaptations in skeletal muscle; however, little is known about the influence of these adaptations on energetics in vivo. We used magnetic resonance spectroscopy to examine the effects of HIT on ATP synthesis from net PCr breakdown (ATPCK), oxidative phosphorylation (ATPOX) and non‐oxidative glycolysis (ATPGLY) in vivo in vastus lateralis during a 24‐s maximal voluntary contraction (MVC).

Estimation of Energy Expenditure during Treadmill Exercise via Thermal Imaging.

PURPOSE Noninvasive imaging of oxygen uptake may provide a useful tool for the quantification of energy expenditure during human locomotion. A novel thermal imaging method (optical flow) was validated against indirect calorimetry for the estimation of energy expenditure during human walking and running. METHODS Fourteen endurance-trained subjects completed a discontinuous incremental exercise test on a treadmill. Subjects performed 4-min intervals at 3, 5, and 7 km·h (walking) and at 8, 10, 12, 14, 16, and 18 km·h (running) with 30 s of rest between intervals. Heart rate, gas exchange, and mean accelerations of ankle, thigh, wrist, and hip were measured throughout the exercise test. A thermal camera (30 frames per second) was used to quantify optical flow, calculated as the movements of the limbs relative to the trunk (internal mechanical work) and vertical movement of the trunk (external vertical mechanical work). RESULTS Heart rate, gross oxygen uptake (mL·kg·min) together with gross and net energy expenditure (J·kg·min) rose with increasing treadmill velocities, as did optical flow measurements and mean accelerations (g) of ankle, thigh, wrist, and hip. Oxygen uptake was linearly correlated with optical flow across all exercise intensities (R = 0.96, P < 0.0001; V˙O2 [mL·kg·min] = 7.35 + 9.85 × optical flow [arbitrary units]). Only 3-4 s of camera recording was required to estimate an optical flow value at each velocity. CONCLUSIONS Optical flow measurements provide an accurate estimation of energy expenditure during horizontal walking and running. The technique offers a novel experimental method of estimating energy expenditure during human locomotion, without use of interfering equipment attached to the subject.

Breaking up Prolonged Sitting does not Alter Postprandial Glycemia in Young, Normal-Weight Men and Women

A randomized, controlled, cross-over study was used to investigate the effects of breaking up prolonged sitting with low intensity physical activity on postprandial blood glucose concentrations in healthy, young, normal-weight adults. 14 men (n=6) and women (n=8) were assigned to 2.5 h of prolonged sitting (CON) and 2.5 h of prolonged sitting with 2-min bouts of walking every 20 min (LIPA). After ingesting a standardized test drink, capillary blood was sampled every 10 min to establish a postprandial blood glucose profile. Based on individual glucose responses, peak blood glucose, time-to-peak glucose, and incremental area under the glucose curve (iAUC) were determined. Paired sample t-tests were used to detect differences between trials. Peak blood glucose (p=0.55) and iAUC (CON: 252 mmol·L-1·2.5 h-1 [163-340]; LIPA: 214 mmol·L-1·2.5 h-1 [146-282]; p=0.45) were not different between trials. Also, time-to-peak glucose was not different between LIPA and CON (p=0.37). Taking advantage of high temporal resolution blood glucose profiles, we showed that breaking up prolonged sitting with low-intensity physical activity does not alter the postprandial blood glucose response in young, healthy, normal-weight adults. Our results indicate that postprandial glycemic control is maintained during prolonged sitting in young, healthy adults.

Blood flow after contraction and cuff occlusion is reduced in subjects with muscle soreness after eccentric exercise

Delayed onset muscle soreness (DOMS) occurs within 1‐2 days after eccentric exercise, but the mechanism mediating hypersensitivity is unclear. This study hypothesized that eccentric exercise reduces the blood flow response following muscle contractions and cuff occlusion, which may result in accumulated algesic substances being a part of the sensitization in DOMS. Twelve healthy subjects (five women) performed dorsiflexion exercise (five sets of 10 repeated eccentric contractions) in one leg, while the contralateral leg was the control. The maximal voluntary contraction (MVC) of the tibialis anterior muscle was recorded. Blood flow was assessed by ultrasound Doppler on the anterior tibialis artery (ATA) and within the anterior tibialis muscle tissue before and immediately after 1‐second MVC, 5‐seconds MVC, and 5‐minutes thigh cuff occlusion. Pressure pain thresholds (PPTs) were recorded on the tibialis anterior muscle. All measures were done bilaterally at day 0 (pre‐exercise), day 2, and day 6 (post‐exercise). Subjects scored the muscle soreness on a Likert scale for 6 days. Eccentric exercise increased Likert scores at day 1 and day 2 compared with day 0 (P<.001). Compared with pre‐exercise (day 0), reduced PPT (~25%, P<.002), MVC (~22%, P<.002), ATA diameter (~8%, P<.002), ATA post‐contraction/occlusion blood flow (~16%, P<.04), and intramuscular peak blood flow (~23%, P<.03) were found in the DOMS leg on day 2 but not in the control leg. These results showed that eccentric contractions decreased vessel diameter, impaired the blood flow response, and promoted hyperalgesia. Thus, the results suggest that the blood flow reduction may be involved in the increased pain response after eccentric exercise.

The impact of husbands' prostate cancer diagnosis and participation in a behavioral lifestyle intervention on spouses' lives and relationships with their partners

Background: A prostate cancer diagnosis affects the patient and his spouse. Partners of cancer patients are often the first to respond to the demands related to their husband’s illness and thus are likely to be the most supportive individuals available to the patients. It is therefore important to examine how spouses react and handle their husband’s prostate cancer diagnosis. Objective: The aim of this study was to explore how the prostate cancer diagnosis and the participation in their partners’ behavioral lifestyle intervention program influenced the spouses’ life, their relationship with their partner, and how they handle the situation. Methods: Interviews were recorded with 8 spouses of potential low-risk prostate cancer patients on active surveillance as part of a clinical self-management lifestyle trial. Results: We identified 3 phases that the spouses went through: feeling insecure about their situation, coping strategies to deal with these insecurities, and feeling reassured. Conclusions: The framework of a clinical trial should include mobilizing spousal empowerment so that they can take on an active and meaningful role in relation to their husband’s disease. The observations here substantiate that the framework of active surveillance in combination with a lifestyle intervention in 1 specific prostate cancer clinical trial can mobilize spousal empowerment. Implications for Practice: Creating well-designed clinical patient programs that actively involve the spouse appears to promote empowerment (meaning, self-efficacy, positive impact, and self-determination) in spouses. Spousal participation in clinical patient programs can give spouses relief from anxieties while recognizing them as a vital support for their husband.