Lower basal and postprandial muscle protein synthesis after 2 weeks single-leg immobilization in older men: No protective effect of anti-inflammatory medication.

Muscle inactivity may reduce basal and postprandial muscle protein synthesis (MPS) rates in humans. Anti-inflammatory treatment alleviates the MPS impairments in younger individuals. The present study explored the influence of nonsteroidal anti-inflammatory drugs (NSAIDs) upon MPS during a period of inactivity in older humans. Eighteen men (age 60-80 years) were allocated to ibuprofen (1200 mg/day, Ibu) or control (Plc) groups. One lower limb was cast immobilized for 2 weeks. Postabsorptive and postprandial MPS was measured before and after the immobilization by L-[ring-13 C6 ]-phenylalanine infusion. The protein expression of select anabolic signaling molecules was investigated by western blot. Basal (0.038 ± 0.002%/h and 0.039 ± 0.005%/h, Plc and Ibu, respectively) and postprandial (0.064 ± 0.004%/h and 0.067 ± 0.010%/h, Plc and Ibu, respectively) MPS rate were higher pre-immobilization compared to basal (0.019 ± 0.005%/h and 0.020 ± 0.010%/h, Plc and Ibu, respectively) and postprandial (0.033 ± 0.005%/h and 0.037 ± 0.006%/h, Plc and Ibu, respectively) MPS rate post-immobilization (p < 0.001). NSAID treatment did not affect the suppression of MPS (p > 0.05). The anabolic signaling were in general reduced after immobilization (p < 0.05). These changes were unaffected by NSAID treatment (p > 0.05). Basal and postprandial MPS dropped markedly after 2 weeks of lower limb immobilization. NSAID treatment neither influenced the reduction in MPS nor the anabolic signaling after immobilization in healthy older individuals.

Muscle protein breakdown is impaired during immobilization compared to during a subsequent retraining period in older men: no effect of anti-inflammatory medication.

Muscle inactivity reduces muscle protein synthesis (MPS), whereas a subsequent period of rehabilitation resistance training (retraining) increases MPS. However, less is known regarding muscle protein breakdown (MPB) during such conditions. Furthermore, nonsteroidal anti-inflammatory drugs (NSAIDs) may have a dampening effect on MPB during periods of inactivity in older individuals. Thus, we measured the average MPB, by use of the deuterated water methodology, during an immobilization period and a subsequent retraining period in older individuals with and without NSAID treatment. Eighteen men (60-80 years: range) were randomly assigned to ibuprofen (1200 mg/d, Ibu) or placebo (Plc). One lower limb was immobilized in a cast for 2 weeks and retrained for 2 weeks, and 2 × 20 g of whey protein was ingested daily during both periods. Besides MPB, the protein expression of different muscle degradation signaling molecules was investigated. MPB was lower during immobilization compared to retraining (p < 0.01). NSAID treatment did not affect the MPB rate during immobilization or retraining (p > 0.05). The protein expression of muscle degradation signaling molecules changed during the study intervention but were unaffected by NSAID treatment. The finding that MPB was lower during immobilization than during retraining indicates that an increased MPB may play an important role in the muscle protein remodeling processes taking place within the initial retraining period. Moreover, NSAID treatment did not significantly influence the MPB rate during 2 weeks of lower limb immobilization or during 2 weeks of subsequent retraining in older individuals.

Skeletal muscle adaptation to immobilization and subsequent retraining in elderly men: No effect of anti-inflammatory medication.

BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) may enhance resistance training induced gain in skeletal muscle mass and strength, but it is unknown if NSAIDs affects muscle loss during periods of inactivity in elderly individuals. Thus, we studied the influence of NSAID treatment on human skeletal muscle during immobilization and rehabilitation resistance training (retraining). METHODS: 19 men (60-80yrs, range) were randomly assigned to ibuprofen (1200mg/d, Ibu) or placebo (Plc). One lower limb was immobilized in a cast for 2weeks and retrained for 6weeks. Moreover, whey protein isolate was ingested (2×20g/d) throughout the whole study period. Plasma inflammatory markers, quadriceps muscle mass and strength, and muscle gene expression were investigated. RESULTS: Muscle mass and strength decreased after 2weeks of immobilization (P<0.001), but returned to baseline levels after 2weeks of retraining combined with whey protein supplementation (P<0.001). Furthermore, muscle mass and strength reached beyond baseline levels after 6weeks of retraining (p<0.05), and NSAID did not significantly affect this (p>0.05). No group-differences, but differences over time, were observed for muscle gene expression of proteolytic and anabolic factors. Plasma inflammatory markers were unaffected by the study intervention and NSAID treatment. CONCLUSION: Two weeks of lower limb immobilization lead to a reduction in muscle mass and strength, but these parameters were restored already after2 weeks of retraining and whey protein supplementation. After 6weeks of retraining and whey protein supplementation, muscle mass and strength increased beyond baseline levels, and NSAID treatment did not significantly influence this in elderly.

Effect of growth hormone on aging connective tissue in muscle and tendon: gene expression, morphology, and function following immobilization and rehabilitation.

It is unknown whether loss in musculotendinous tissue during inactivity can be counteracted by growth hormone (GH), and whether GH accelerate rehabilitation in aging individuals. Elderly men (65-75 yr; n = 12) had one leg immobilized 2 wk followed by 6 wk of retraining and were randomly assigned to daily injections of recombinant GH (rhGH; n = 6) or placebo (Plc; n = 6). Cross-sectional area (CSA), muscle strength (MVC), and biomechanical properties of m. quadriceps and patellar tendon were determined. Muscle and tendon biopsies were analyzed for gene expressions (mRNA) of collagen (COL1A1/3A1) and insulin-like growth factors (IGF-1Ea/Ec). Fibril morphology was analyzed by transmission electron microscope (TEM). In tendon, CSA and biomechanical properties did not change following immobilization, but an increase in CSA was found after 6 wk of rehabilitation in both groups. The changes were more pronounced when GH was injected. Furthermore, tendon stiffness increased in the GH group. Muscle CSA declined after immobilization in the Plc but not in the GH group. Muscle CSA increased during retraining, with a significantly larger increase in the GH group compared with the Plc group. Both a time and a group effect were seen for IGF-1Ea/Ec and COL1A1/3A1 mRNA expression in muscle, with a difference between GH and Plc. IGF-1Ea/Ec and COL-1A1/3A1 mRNA expression increased in muscle following immobilization and retraining in subjects receiving GH, whereas an increase in IGF-1Ec mRNA expression was seen in the Plc group only after retraining. In conclusion, in elderly humans, GH seems to have a matrix stabilizing effect during inactivity and rehabilitation by stimulating collagen expression in the musculotendinous tissue and increasing tendon CSA and stiffness.

Tendon and skeletal muscle matrix gene expression and functional responses to immobilisation and rehabilitation in young males: effect of growth hormone administration.

We examined the effect of growth hormone (GH) on connective tissue of tendon and skeletal muscle during immobilisation and re-training in humans. Young men (20-30 years; n = 20) were randomly assigned to daily recombinant human GH (rhGH) (33-50 µg kg(-1) day(-1)) or placebo (Plc), and had one leg immobilised for 2 weeks, followed by 6 weeks of strength training. The cross-sectional area (CSA), maximal muscle strength (maximal voluntary contraction, MVC) and biomechanical properties of the quadriceps muscle and patellar tendon were determined. Muscle and tendon biopsies were analysed for mRNA of collagen (COL1A1/3A1), insulin-like growth factors (IGF-1Ea/Ec), lysyl oxidase (LOX), matrix metalloproteases (MMP-2 and MMP-9), decorin and tenascin-C. Fibril morphology was analysed by transmission electron microscopy (TEM) to detect changes in the fibril diameter distribution. In muscle, CSA and MVC declined with immobilisation and recovered with rehabilitation similarly in both groups. Likewise, both groups showed increased IGF-1Ea/Ec and COL1A1/3A1 expression in muscle during re-training after immobilisation compared with baseline, and the increase was more pronounced when subjects received GH. The tendon CSA did not change during immobilisation, but increased in both groups during 6 weeks of rehabilitation (∼14%). A decline in tendon stiffness after immobilisation was observed only in the Plc group, and an increase during 6 weeks of rehabilitation was observed only in the GH group. IGF-1Ea and COL1A1/3A1 mRNA increased with immobilisation in the GH group only, and LOX mRNA was higher in the GH group than in the Plc group after immobilisation. Both groups showed an increase in MMP-2 with immobilisation, whereas no changes in MMP-9, decorin and tenascin-C were observed. The tendon fibril diameter distribution remained unchanged in both groups. In conclusion, GH stimulates collagen expression in both skeletal muscle and tendon, abolishes the normal inactivity-related decline in tendon stiffness and LOX, and results in increased tendon CSA and stiffness during rehabilitation. GH has a matrix-stabilising effect during periods of inactivity and rehabilitation in humans.