Jared M. Dickinson

Influence of aging on the in vivo properties of human patellar tendon

Tendons are important for optimal muscle force transfer to bone and play a key role in functional ability. Changes in tendon properties with aging could contribute to declines in physical function commonly associated with aging. We investigated the in vivo mechanical properties of the patellar tendon in 37 men and women [11 young (27 +/- 1 yr) and 26 old (65 +/- 1 yr)] using ultrasonography and magnetic resonance imaging (MRI). Patella displacement relative to the tibia was monitored with ultrasonography during ramped isometric contractions of the knee extensors, and MRI was used to determine tendon cross-sectional area (CSA) and signal intensity. At peak force, patellar tendon deformation, stress, and strain were 13 (P = 0.05), 19, and 12% less in old compared with young (P < 0.05). Additionally, deformation, stiffness, stress, CSA, and length were 18, 35, 41, 28, and 11% greater (P < 0.05), respectively, in men compared with women. After normalization of mechanical properties to a common force, no age differences were apparent; however, stress and strain were 26 and 22% higher, respectively, in women compared with men (P < 0.05). CSA and signal intensity decreased 12 and 24%, respectively, with aging (P < 0.05) in the midregion of the tendon. These data suggest that differences in patellar tendon in vivo mechanical properties with aging are more related to force output rather than an age effect. In contrast, the decrease in signal intensity indirectly suggests that the internal milieu of the tendon is altered with aging; however, the physiological and functional consequence of this finding requires further study.

Influence of acetaminophen and ibuprofen on skeletal muscle adaptations to resistance exercise in older adults

Evidence suggests that consumption of over-the-counter cyclooxygenase (COX) inhibitors may interfere with the positive effects that resistance exercise training has on reversing sarcopenia in older adults. This study examined the influence of acetaminophen or ibuprofen consumption on muscle mass and strength during 12 wk of knee extensor progressive resistance exercise training in older adults. Thirty-six individuals were randomly assigned to one of three groups and consumed the COX-inhibiting drugs in double-blind placebo-controlled fashion: placebo (67 ± 2 yr; n = 12), acetaminophen (64 ± 1 yr; n = 11; 4 g/day), and ibuprofen (64 ± 1 yr; n = 13; 1.2 g/day). Compliance with the resistance training program (100%) and drug consumption (via digital video observation, 94%), and resistance training intensity were similar (P > 0.05) for all three groups. Drug consumption unexpectedly increased muscle volume (acetaminophen: 109 ± 14 cm(3), 12.5%; ibuprofen: 84 ± 10 cm(3), 10.9%) and muscle strength (acetaminophen: 19 ± 2 kg; ibuprofen: 19 ± 2 kg) to a greater extent (P < 0.05) than placebo (muscle volume: 69 ± 12 cm(3), 8.6%; muscle strength: 15 ± 2 kg), when controlling for initial muscle size and strength. Follow-up analysis of muscle biopsies taken from the vastus lateralis before and after training showed muscle protein content, muscle water content, and myosin heavy chain distribution were not influenced (P > 0.05) by drug consumption. Similarly, muscle content of the two known enzymes potentially targeted by the drugs, COX-1 and -2, was not influenced (P > 0.05) by drug consumption, although resistance training did result in a drug-independent increase in COX-1 (32 ± 8%; P < 0.05). Drug consumption did not influence the size of the nonresistance-trained hamstring muscles (P > 0.05). Over-the-counter doses of acetaminophen or ibuprofen, when consumed in combination with resistance training, do not inhibit and appear to enhance muscle hypertrophy and strength gains in older adults. The present findings coupled with previous short-term exercise studies provide convincing evidence that the COX pathway(s) are involved in the regulation of muscle protein turnover and muscle mass in humans.

Protein synthesis and the expression of growth-related genes are altered by running in human vastus lateralis and soleus muscles

Recent evidence suggests aerobic exercise may help preserve soleus muscle mass during unloading. The purpose of this investigation was to examine the muscle-specific metabolic response to running as it relates to muscle growth. Mixed-muscle protein synthesis [fractional synthetic rate (FSR)] and gene expression (GE) were examined in the vastus lateralis (VL) and soleus (SOL) muscles from eight men (26 +/- 2 yr; Vo(2max) 63 +/- 2 ml.kg(-1).min(-1)) before and after a 45-min level-grade treadmill run at 77 +/- 1% intensity. Muscle glycogen utilization was similar between muscles. Resting FSR was similar between the VL (0.080 +/- 0.007 %/h) and SOL (0.086 +/- 0.008 %/h) and was higher (P < 0.05) 24 h postexercise compared with rest for both muscles. The absolute change in FSR was not different between muscles (0.030 +/- 0.007 vs. 0.037 +/- 0.012 %/h for VL and SOL). At baseline, myostatin GE was approximately twofold higher (P < 0.05) in SOL compared with VL, while no other muscle-specific differences in GE were present. After running, myostatin GE was suppressed (P < 0.05) in both muscles at 4 h and was higher (P < 0.05) than baseline at 24 h for VL only. Muscle regulatory factor 4 mRNA was elevated (P < 0.05) at 4 h in both SOL and VL; MyoD and peroxisome-proliferator-activated receptor-gamma coactivator-1alpha (PGC-1alpha) were higher (P < 0.05) at 4 h, and forkhead box [FOXO]3A was higher at 24 h in SOL only, while muscle-RING-finger protein-1 (MuRF-1) was higher (P < 0.05) at 4 h in VL only. Myogenin and atrogin-1 GE were unaltered. The similar increases between muscles in FSR support running as part of the exercise countermeasure to preserve soleus mass during unloading. The subtle differences in GE suggest a potential mechanism for muscle-specific adaptations to chronic run training.

Effect of a cyclooxygenase-2 inhibitor on postexercise muscle protein synthesis in humans

Nonselective blockade of the cyclooxygenase (COX) enzymes in skeletal muscle eliminates the normal increase in muscle protein synthesis following resistance exercise. The current study tested the hypothesis that this COX-mediated increase in postexercise muscle protein synthesis is regulated specifically by the COX-2 isoform. Sixteen males (23 +/- 1 yr) were randomly assigned to one of two groups that received three doses of either a selective COX-2 inhibitor (celecoxib; 200 mg/dose, 600 mg total) or a placebo in double-blind fashion during the 24 h following a single bout of knee extensor resistance exercise. At rest and 24 h postexercise, skeletal muscle protein fractional synthesis rate (FSR) was measured using a primed constant infusion of [(2)H(5)]phenylalanine coupled with muscle biopsies of the vastus lateralis, and measurements were made of mRNA and protein expression of COX-1 and COX-2. Mixed muscle protein FSR in response to exercise (P < 0.05) was not suppressed by the COX-2 inhibitor (0.056 +/- 0.004 to 0.108 +/- 0.014%/h) compared with placebo (0.074 +/- 0.004 to 0.091 +/- 0.005%/h), nor was there any difference (P > 0.05) between the placebo and COX-2 inhibitor postexercise when controlling for resting FSR. The COX-2 inhibitor did not influence COX-1 mRNA, COX-1 protein, or COX-2 protein levels, whereas it did increase (P < 0.05) COX-2 mRNA (3.0 +/- 0.9-fold) compared with placebo (1.3 +/- 0.3-fold). It appears that the elimination of the postexercise muscle protein synthesis response by nonselective COX inhibitors is not solely due to COX-2 isoform blockade. Furthermore, the current data suggest that the COX-1 enzyme is likely the main isoform responsible for the COX-mediated increase in muscle protein synthesis following resistance exercise in humans.

Influence of acetaminophen and ibuprofen on in vivo patellar tendon adaptations to knee extensor resistance exercise in older adults

Millions of older individuals consume acetaminophen or ibuprofen daily and these same individuals are encouraged to participate in resistance training. Several in vitro studies suggest that cyclooxygenase-inhibiting drugs can alter tendon metabolism and may influence adaptations to resistance training. Thirty-six individuals were randomly assigned to a placebo (67 ± 2 yr old), acetaminophen (64 ± 1 yr old; 4,000 mg/day), or ibuprofen (64 ± 1 yr old; 1,200 mg/day) group in a double-blind manner and completed 12 wk of knee extensor resistance training. Before and after training in vivo patellar tendon properties were assessed with MRI [cross-sectional area (CSA) and signal intensity] and ultrasonography of patellar tendon deformation coupled with force measurements to obtain stiffness, modulus, stress, and strain. Mean patellar tendon CSA was unchanged (P > 0.05) with training in the placebo group, and this response was not influenced with ibuprofen consumption. Mean tendon CSA increased with training in the acetaminophen group (3%, P < 0.05), primarily due to increases in the mid (7%, P < 0.05) and distal (8%, P < 0.05) tendon regions. Correspondingly, tendon signal intensity increased with training in the acetaminophen group at the mid (13%, P < 0.05) and distal (15%, P = 0.07) regions. When normalized to pretraining force levels, patellar tendon deformation and strain decreased 11% (P < 0.05) and stiffness, modulus, and stress were unchanged (P > 0.05) with training in the placebo group. These responses were generally uninfluenced by ibuprofen consumption. In the acetaminophen group, tendon deformation and strain increased 20% (P < 0.05) and stiffness (-17%, P < 0.05) and modulus (-20%, P < 0.05) decreased with training. These data suggest that 3 mo of knee extensor resistance training in older adults induces modest changes in the mechanical properties of the patellar tendon. Over-the-counter doses of acetaminophen, but not ibuprofen, have a strong influence on tendon mechanical and material property adaptations to resistance training. These findings add to a growing body of evidence that acetaminophen has profound effects on peripheral tissues in humans.

A new method to study in vivo protein synthesis in slow- and fast-twitch muscle fibers and initial measurements in humans

The aim of this study was to develop an approach to directly assess protein fractional synthesis rate (FSR) in isolated human muscle fibers in a fiber type-specific fashion. Individual muscle fibers were isolated from biopsies of the vastus lateralis (VL) and soleus (SOL) obtained from eight young men during a primed, continuous infusion of [5,5,5-(2)H3]leucine performed under basal conditions. To determine mixed protein FSR, a portion of each fiber was used to identify fiber type, fibers of the same type were pooled, and the [5,5,5-(2)H3]leucine enrichment was determined via GC-MS. Processing isolated slow-twitch [myosin heavy chain (MHC) I] and fast-twitch (MHC IIa) fibers for mixed protein bound [5,5,5-(2)H3]leucine enrichment yielded mass ion chromatographic peaks that were similar in shape, abundance, and measurement reliability as tissue homogenates. In the VL, MHC I fibers exhibited a 33% faster (P<0.05) mixed protein FSR compared with MHC IIa fibers (0.068+/-0.006 vs. 0.051+/-0.003%/h). MHC I fibers from the SOL (0.060+/-0.005%/h) and MHC I fibers from the VL displayed similar (P>0.05) mixed protein FSR. Feasibility of processing isolated human muscle fibers for analysis of myofibrillar protein [5,5,5-(2)H3]leucine enrichment was also confirmed in non-fiber-typed pooled fibers from the VL. These methods can be applied to the study of fiber type-specific responses in human skeletal muscle. The need for this level of investigation is underscored by the different contributions of each fiber type to whole muscle function and the numerous distinct adaptive functional and metabolic changes in MHC I and MHC II fibers originating from the same muscle.

Influence of tracer selection on protein synthesis rates at rest and postexercise in multiple human muscles

The goal of this investigation was to assess the influence of tracer selection on mixed muscle fractional synthesis rate (FSR) at rest and postexercise during amino acid infusion in multiple human skeletal muscles. Fractional synthesis rate was measured before and 24 hours after 45 minutes of running using simultaneous infusion of [(2)H(5)]-phenylalanine (Phe) and [(2)H(3)]-leucine (Leu) coupled with muscle biopsies from the vastus lateralis and soleus in aerobically trained men (n = 8; age, 26 ± 2 years). Mixed muscle protein FSR was analyzed by gas chromatography-mass spectrometry combined with a standard curve using the enriched muscle tissue fluid as the precursor pool. To control for potential analytical differences between tracers, all samples and standards for both tracers were matched for m + 0 abundance. Tracer selection did not influence resting FSR for the vastus lateralis or soleus (P > .05). Fractional synthesis rate measured 24 hours postexercise was higher (P < .05) compared with rate at rest and was similar between tracers for the vastus lateralis (Phe, 0.110% ± 0.010%·h(-1); Leu, 0.109% ± 0.005%·h(-1)) and soleus (Phe, 0.123% ± 0.008%·h(-1); Leu, 0.122% ± 0.005%·h(-1)). These data demonstrate that tracer selection does not influence the assessment of resting or postexercise FSR, thereby supporting the use of both [(2)H(5)]-phenylalanine and [(2)H(3)]-leucine for the measurement of FSR in exercise-based studies of human skeletal muscle.