Predictors of skeletal muscle mass in elderly men and women

BACKGROUND: Elderly men and women lose muscle mass and strength with increasing age. Decreased physical activity, hormones, malnutrition and chronic disease have been identified as factors contributing to this loss. There are few data, however, for their multivariate associations with muscle mass and strength. This study analyzes these associations in a cross-sectional sample of elderly people from the New Mexico Aging Process Study. METHODS: Data collected in 1994 for 121 male and 180 female volunteers aged 65-97 years of age enrolled in The New Mexico Aging Process Study were analyzed. Body composition was measured using dual energy X-ray absorptiometry; dietary intake from 3 day food records; usual physical activity by questionnaire; health status from annual physical examinations; and serum testosterone, estrone, sex-hormone binding globulin (SHBG), and insulin-like growth factor (IGF1) from radioimmunoassays of fasting blood samples. Statistical analyses included partial correlation and stepwise multiple regression. RESULTS: The muscle mass and strength (adjusted for knee height) decreased with increasing age in both sexes. The muscle mass was significantly associated with serum free-testosterone, physical activity, cardiovascular disease, and IGF1 in the men. In the women, the muscle mass was significantly associated with total fat mass and physical activity. Age was not associated significantly with muscle mass after controlling for these variables. Grip strength was associated with age independent of muscle mass in both sexes. Estrogen (endogenous and exogenous) was not associated with muscle mass or strength in women. CONCLUSIONS: Age-related loss of muscle mass and strength occurs in relatively healthy, well-nourished elderly men and women and has a multifactorial basis. Sex hormone status is an important factor in men but not in women. Physical activity is an important predictor of muscle mass in both sexes.     

Resistance exercise-induced increases in putative anabolic hormones do not enhance muscle protein synthesis or intracellular signalling in young men

We aimed to determine whether exercise-induced elevations in systemic concentration of testosterone, growth hormone (GH) and insulin-like growth factor-1 (IGF-1) enhanced post-exercise myofibrillar protein synthesis (MPS) and phosphorylation of signalling proteins important in regulating mRNA translation. Eight young men (20 ± 1.1 years, BMI = 26 ± 3.5 kg m⁻²) completed two exercise protocols designed to maintain basal hormone concentrations (low hormone, LH) or elicit increases in endogenous hormones (high hormone, HH). In the LH protocol, participants performed a bout of unilateral resistance exercise with the elbow flexors. The HH protocol consisted of the same elbow flexor exercise with the contralateral arm followed immediately by high-volume leg resistance exercise. Participants consumed 25 g of protein after arm exercise to maximize MPS. Muscle biopsies and blood samples were taken as appropriate. There were no changes in serum testosterone, GH or IGF-1 after the LH protocol, whereas there were marked elevations after HH (testosterone, P < 0.001; GH, P < 0.001; IGF-1, P < 0.05). Exercise stimulated a rise in MPS in the biceps brachii (rest = 0.040 ± 0.007, LH = 0.071 ± 0.008, HH = 0.064 ± 0.014% h⁻¹; P < 0.05) with no effect of elevated hormones ( P = 0.72). Phosphorylation of the 70 kDa S6 protein kinase (p70S6K) also increased post-exercise ( P < 0.05) with no differences between conditions. We conclude that the transient increases in endogenous purportedly anabolic hormones do not enhance fed-state anabolic signalling or MPS following resistance exercise. Local mechanisms are likely to be of predominant importance for the post-exercise increase in MPS.     

Age-related differences in the dose–response relationship of muscle protein synthesis to resistance exercise in young and old men

We investigated how myofibrillar protein synthesis (MPS) and muscle anabolic signalling were affected by resistance exercise at 20–90% of 1 repetition maximum (1 RM) in two groups (25 each) of post-absorptive, healthy, young (24 ± 6 years) and old (70 ± 5 years) men with identical body mass indices (24 ± 2 kg m⁻²). We hypothesized that, in response to exercise, anabolic signalling molecule phosphorylation and MPS would be modified in a dose-dependant fashion, but to a lesser extent in older men. Vastus lateralis muscle was sampled before, immediately after, and 1, 2 and 4 h post-exercise. MPS was measured by incorporation of [1,2-¹³C] leucine (gas chromatography–combustion–mass spectrometry using plasma [1,2-¹³C]α-ketoisocaparoate as surrogate precursor); the phosphorylation of p70 ribosomal S6 kinase (p70s6K) and eukaryotic initiation factor 4E binding protein 1 (4EBP1) was measured using Western analysis with anti-phosphoantibodies. In each group, there was a sigmoidal dose–response relationship between MPS at 1–2 h post-exercise and exercise intensity, which was blunted ( P < 0.05) in the older men. At all intensities, MPS fell in both groups to near-basal values by 2–4 h post-exercise. The phosphorylation of p70s6K and 4EBP1 at 60–90% 1 RM was blunted in older men. At 1 h post-exercise at 60–90% 1 RM, p70s6K phosphorylation predicted the rate of MPS at 1–2 h post-exercise in the young but not in the old. The results suggest that in the post-absorptive state: (i) MPS is dose dependant on intensity rising to a plateau at 60–90% 1 RM; (ii) older men show anabolic resistance of signalling and MPS to resistance exercise.     

Effect of exercise training on muscle glucose transporter 4 protein and intramuscular lipid content in elderly men with impaired glucose tolerance

This study determined the effects of exercise training on adaptations of skeletal muscle including fibre composition, capillarity, intra-muscular triglyceride concentration (IMTG), as well as glucose transporter 4 protein (GLUT4) and metabolic enzyme activities. Percutaneous muscle biopsies from the vastus lateralis muscle were obtained from non-obese elderly Korean men (n=10; age range 58–67 years) with impaired glucose tolerance. Subjects performed 12 weeks of endurance exercise training (60–70% of the heart rate reserve). The training program improved the total GLUT4 protein expression (P<0.01), decreased the IMTG, increased the fatty acid oxidation capacity, and the number of capillaries around type 1 fibres (P<0.05), whereas no significant alteration was observed around type II fibres. All data are presented as the means together with the standard deviation. The results suggest that endurance training evokes morphological and biochemical changes in the skeletal muscle of elderly men with impaired glucose tolerance that may be considered to limit the development of type 2 diabetes.     

抗阻训练与蛋白质补充：改善老年人肌肉蛋白质代谢

背景：老年人肌肉蛋白质代谢出现了负平衡状态,这被认为是老年人肌肉丢失和肌肉功能衰退的重要原因。近年来的许多研究都证实,抗阻训练和蛋白质补充可以有效地改善老年人肌肉蛋白质代谢的负平衡现象,并提高老年人肌肉质量,改善其肌肉功能。 目的：综述老年人抗阻训练、蛋白质补充以及抗阻训练结合蛋白质补充对老年人肌肉蛋白质代谢和肌肉功能的影响,探讨改善老年人肌肉功能和抑制肌肉丢失的可行办法。 方法：应用计算机检索CNKI 期刊全文数据库(2005年1月至2012年12月)和PubMed数据库(2010年1月至2012年12月)与肌肉蛋白质代谢、蛋白补充及抗阻训练对老年人肌肉蛋白质代谢影响的相关文献。检索词分别为“蛋白质代谢;肌细胞;肌肉丢失;抗阻训练;蛋白补充”和“muslce cell, resistance training,Sarcopenia,protein motablism”。 结果与结论：在检索到的81篇文献中排除22篇不符合标准的文献,最终纳入59篇文献进行了分析、综述。结果表明,老年人肌肉蛋白质代谢的负平衡状态是导致老年肌肉丢失的直接原因。抗阻训练和给予富含亮氨酸的蛋白质补充能够有效增强老年人肌肉蛋白质合成代谢水平,并改善老年人肌肉功能。但老年人肌肉蛋白合成代谢对抗阻训练和蛋白补充的反应能力远低于年轻人。     

Function, morphology and protein expression of ageing skeletal muscle: a cross-sectional study of elderly men with different training backgrounds

The function and morphology of knee extension/m. vastus lateralis and elbow flexion/m. biceps brachii were studied in young (28 +/- 0.1 years, n = 7) and elderly (68 +/- 0.5 years, n = 8) sedentary subjects and in elderly swimmers (69 +/- 1.9 years, n = 6), runners (70 +/- 0.7 years, n = 5) and strength-trained subjects (68 +/- 0.8 years, n = 7). On average, the training groups had, for the 12-17 years before the measurements were taken, performed their training regimen 3 +/- 0.1 times a week. Compared with the young subjects, the maximal isometric torque of the sedentary elderly subjects was 44% (P less than 0.05) lower in knee extension and 32% (P less than 0.05) lower in elbow flexion, and speed of movement was between 20 and 26% (P less than 0.05) lower in both knee extension and elbow flexion. The cross-sectional area of m. quadriceps femoris and the elbow flexors was also 24% (P less than 0.05) and 20% lower respectively, and the specific tension was 27% (P less than 0.05) lower in m. quadriceps femoris and 14% (P less than 0.05) lower in the elbow flexors. A 27% (P less than 0.05) higher content of myosin heavy chain type I and a 39% (P less than 0.05) higher content of the slow-type myosin light chain--2 was observed in m. vastus lateralis of the sedentary elderly subjects as compared with the young subjects. The same tendency was also seen with m. biceps brachii. Since the histochemical fibre-type distribution was identical and no major co-expression of type I and type II myosin heavy-chain isoforms was observed with immunocytochemistry, the increase in slow myosin isoforms with ageing seems mainly related to a larger relative area of type I fibres, induced by a selective atrophy of type II fibre area. An increased content of the beta-isoform of tropomyosin was also demonstrated with ageing. In contrast to the swimmers and runners, the elderly strength-trained subjects had maximal isometric torques, speed of movements, cross-sectional areas, specific tensions and a content of myosin and tropomyosin isoforms in both muscles studied identical to those of the young controls. These results seem to suggest that strength training can counteract the age-related changes in function and morphology of the ageing human skeletal muscle.     

Creatine supplementation improves muscular performance in older women

Muscle power and strength decrease with age leading to reduced independence and increased health risk from falls. Creatine supplementation can increase muscle power and strength. The purpose of this study was to examine the effects of 7 days of creatine supplementation on body composition, muscular strength, and lower-body motor functional performance in older women. Thirty 58–71 year old women performed three test sessions (T1–T3) each separated by one week. Each session consisted of one repetition maximum tests for bench press and leg press, and isometric hand-grip, tandem gait, upper-body ergometer, and lower-body ergometer tests. Following T2, subjects were assigned to a creatine monohydrate (0.3 g kg body mass⁻¹ for 7 days) (CR: 63.31 ± 1.22 year, 160.00 ± 1.58 cm, 67.11 ± 4.38 kg) or a placebo (PL: 62.98 ± 1.11 year, 162.25 ± 2.09 cm, 67.84 ± 3.90 kg) supplementation group. CR significantly (P < 0.05) increased bench press (1.7 ± 0.4 kg), leg press (5.2 ± 1.8 kg), body mass (0.49 ± 0.04 kg) and fat free mass (0.52 ± 0.05) and decreased completion time on the functional tandem gait tests from T2–T3. No significant changes were found for PL on any of the measured variables. No adverse side-effects were reported by either group. Short-term creatine supplementation resulted in an increase in strength, power, and lower-body motor functional performance in older women without any adverse side effects     

N-Methyl-D-aspartate receptor activation inhibits protein synthesis in cortical neurons independently of its ionic permeability properties

Transient cerebral ischemia, which is accompanied by a sustained release of glutamate, strongly depresses protein synthesis. We have previously demonstrated in cortical neurons that a glutamate-induced increase in intracellular Ca(2+) is likely responsible for the blockade of the elongation step of protein synthesis. In this study, we provide evidence indicating that NMDA mobilizes a thapsigargin-sensitive pool of intracellular Ca(2+). Exposure of cortical neurons to NMDA, in the absence of external Ca(2+), produced a transient rise in intracellular Ca(2+) that was suppressed by pretreatment with thapsigargin. This rise in intracellular Ca(2+) did not result from an influx of Na(+) via reversal of the mitochondrial Na(+)/Ca(2+) exchanger since it persisted in a Na(+)-free medium or in the presence of CGP 37157, an inhibitor of the exchanger. Moreover, the NMDA-induced increase in intracellular Ca(2+) required the presence of D-serine, was blocked by D(-)-2-amino-5-phosphonopentanoic acid, but was not reduced in the presence of external Mg(2+). This unexpected non-ionotropic effect of NMDA was associated with an inhibition of protein synthesis that was also insensitive to the absence of external Ca(2+) or Na(+), or presence of Mg(2+). NMDA treatment resulted in an increase in the phosphorylation of eEF-2 in the absence or presence of external Ca(2+). The initiation step of protein synthesis was not blocked by NMDA since the phosphorylation of initiation factor eIF-2alpha subunit was not altered by NMDA treatment. In conclusion, we provide evidence indicating that NMDA can inhibit protein synthesis in cortical neurons through a process that involves the mobilization of intracellular Ca(2+) stores via a mechanism that is not linked to the ionic properties of NMDA receptors.     

Nutrient signalling in the regulation of human muscle protein synthesis

The mammalian target of rapamycin (mTOR) and AMP-activated protein kinase (AMPK) are important nutrient- and energy-sensing and signalling proteins in skeletal muscle. AMPK activation decreases muscle protein synthesis by inhibiting mTOR signalling to regulatory proteins associated with translation initiation and elongation. On the other hand, essential amino acids (leucine in particular) and insulin stimulate mTOR signalling and protein synthesis. We hypothesized that anabolic nutrients would be sensed by both AMPK and mTOR, resulting in an acute and potent stimulation of human skeletal muscle protein synthesis via enhanced translation initiation and elongation.
We measured muscle protein synthesis and mTOR-associated upstream and downstream signalling proteins in young male subjects ( n = 14) using stable isotopic and immunoblotting techniques. Following a first muscle biopsy, subjects in the 'Nutrition' group ingested a leucine-enriched essential amino acid–carbohydrate mixture (EAC). Subjects in the Control group did not consume nutrients. A second biopsy was obtained 1 h later. Ingestion of EAC significantly increased muscle protein synthesis, modestly reduced AMPK phosphorylation, and increased Akt/PKB (protein kinase B) and mTOR phosphorylation ( P < 0.05). mTOR signalling to its downstream effectors (S6 kinase 1 (S6K1) and 4E-binding protein 1 (4E-BP1) phosphorylation status) was also increased ( P < 0.05). In addition, eukaryotic elongation factor 2 (eEF2) phosphorylation was significantly reduced ( P < 0.05). Protein synthesis and cell signalling (phosphorylation status) was unchanged in the control group ( P > 0.05).
We conclude that anabolic nutrients alter the phosphorylation status of both AMPK- and mTOR-associated signalling proteins in human muscle, in association with an increase in protein synthesis not only via enhanced translation initiation but also through signalling promoting translation elongation.     

Bacteriuria in elderly institutionalized men

Over a two-year period we obtained monthly urine samples from all noncatheterized male residents on two geriatric wards to determine the occurrence and optimal management of bacteriuria in this population. Among 88 men the prevalence of bacteriuria was 33 per cent, and the incidence was 45 infections per 100 patients per year. Outcomes after single-dose therapy for asymptomatic bacteriuria with 43 courses of trimethoprim/sulfamethoxazole and 23 of tobramycin included 15 cures, 40 relapses, and 11 treatment failures. Thirty-six residents who had a relapse or in whom single-dose therapy failed were randomly assigned to receive therapy to eradicate bacteriuria or to receive no therapy. All 20 residents who received no therapy remained bacteriuric. The 16 residents who received therapy had fewer months of bacteriuria after randomization, but at the end of the study only one remained free of bacteriuria. Mortality and infectious morbidity after randomization were similar in the two groups. These data suggest that asymptomatic bacteriuria is common in elderly institutionalized men and that therapy is neither necessary nor effective.     

Human soleus muscle protein synthesis following resistance exercise

AIM: It is generally believed the calf muscles in humans are relatively unresponsive to resistance training when compared with other muscles of the body. The purpose of this investigation was to determine the muscle protein synthesis response of the soleus muscle following a standard high intensity bout of resistance exercise. METHODS: Eight recreationally active males (27 +/- 4 years) completed three unilateral calf muscle exercises: standing calf press/heel raise, bent-knee calf press/heel raise, and seated calf press/heel raise. Each exercise consisted of four sets of 15 repetitions (approximately 15 repetition maximum, RM, or approximately 70% 1RM). Fractional rate of muscle protein synthesis (FSR) was determined with a primed constant infusion of [2H5]phenylalanine coupled with muscle biopsies immediately and 3 h following the exercise in both the exercise and non-exercise (resting control) leg. RESULTS: FSR was elevated (P < 0.05) in the exercise (0.069 +/- 0.010) vs. the control (0.051 +/- 0.012) leg. Muscle glycogen concentration was lower (P < 0.05) in the exercise compared with the control leg (Decrease from control; immediate post-exercise: 54 +/- 5; 3 h post-exercise: 36 +/- 4 mmol kg(-1) wet wt.). This relatively high amount of glycogen use is comparable with previous studies of resistance exercise of the thigh (i.e. vastus lateralis; approximately 41-49 mmol kg(-1) wet wt.). However, the exercise-induced increase in FSR that has been consistently reported for the vastus lateralis (approximately 0.045-0.060% h(-1)) is on average approximately 200% higher than reported here for the soleus (0.019 +/- 0.003% h(-1)). CONCLUSIONS: These results suggest the relatively poor response of soleus muscle protein synthesis to an acute bout of resistance exercise may be the basis for the relative inability of the calf muscles to respond to resistance training programs.     

Management of osteoporosis in elderly men

Osteoporosis is a common condition associated with aging but has been considered to primarily affect women because of the substantial effect of menopause on osteoporosis. Bone density can decrease with aging in men but occurs more gradually than in postmenopausal women. With improvements in healthcare and extended life expectancy, it is becoming more apparent that osteoporosis affects men and can have serious consequences. Recently, a greater number of osteoporosis studies are either including men or focusing specifically on them. The majority of medication trials in men, however, used bone density as the primary outcome rather than fractures. Therefore, treatment data for men is still rather limited, and there is also very little information in the oldest subset of this population. The more recent guidelines for treating osteoporosis now include men, but the recommendations for screening and treatment are not necessarily gender specific. Despite the limited data, some osteoporosis treatments have received approval to treat or prevent osteoporosis specifically in men. Future studies must provide greater information on fracture prevention in men and also must include a greater population of the oldest geriatric patients, who are typically not well represented in osteoporosis trials, to evaluate any differences in both efficacy and side effects. The oldest group is important because they are at the highest risk for both osteoporosis-related complications and treatment-related adverse events.     

The effect of unloading on protein synthesis in human skeletal muscle

Atrophy of skeletal muscle is observed in response to immobilization and lack of weight-bearing. The aim of this study was to investigate the effect of immobilization on muscle protein synthesis and associated biochemical parameters in skeletal muscle of healthy volunteers employing a standardized model of lower limb unloading. One leg was unloaded for 10 days, and percutaneous muscle biopsies were taken before and at the end of the unloading period. The capacity for protein synthesis, as reflected by the concentration of RNA, decreased by 16% (P < 0.05) although the fractional synthesis rate (FSR) of protein was not significantly changed after 10 days of unloading. Furthermore there was an increase in the concentration of the free branched chain amino acids in muscle by 48% (P < 0.05).     

Oral tyrosine supplementation improves exercise capacity in the heat

Increased brain dopamine availability improves prolonged exercise tolerance in the heat. It is unclear whether supplementing the amino-acid precursor of dopamine increases exercise capacity in the heat. Eight healthy male volunteers [mean age 32 ± 11 (SD) years; body mass 75.3 ± 8.1 kg; peak oxygen uptake ([(V)\dot]O_2peak \dot{V}O_{{2peak}} ) 3.5 ± 0.3 L min⁻¹] performed two exercise trials separated by at least 7 days in a randomised, crossover design. Subjects consumed 500 mL of a flavoured sugar-free drink (PLA), or the same drink with 150 mg kg body mass⁻¹ tyrosine (TYR) in a double-blind manner 1 h before cycling to exhaustion at a constant exercise intensity equivalent to 68 ± 5% [(V)\dot]O_2peak \dot{V}O_{{2peak}} in 30°C and 60% relative humidity. Pre-exercise plasma tyrosine:large neutral amino acids increased 2.9-fold in TYR (P < 0.01), while there was no change in PLA (P > 0.05). Subjects cycled longer in TYR compared to PLA (80.3 ± 19.7 min vs. 69.2 ± 14.0 min; P < 0.01). Core temperature, mean weighted skin temperature, heart rate, ratings of perceived exertion and thermal sensation were similar in TYR and PLA during exercise and at exhaustion (P > 0.05) despite longer exercise time in TYR. The results show that acute tyrosine supplementation is associated with increased endurance capacity in the heat in moderately trained subjects. The results also suggest for the first time that the availability of tyrosine, a nutritional dopamine precursor, can influence the ability to subjectively tolerate prolonged submaximal constant-load exercise in the heat.     

Dietary supplementation with whey protein improves systemic microvascular function in heart failure patients: a pilot study

Endothelial dysfunction is a well-known component of the pathophysiology of heart failure (HF), with proven prognostic value. Dietary supplementation with whey protein (WP) has been widely used to increase skeletal muscle mass, but it also has vascular effects, which are less understood. This study aimed to evaluate the effects of WP supplementation on the systemic microvascular function of HF patients. This was a blinded, randomized, placebo-controlled clinical trial that evaluated the effects of 12-week WP dietary supplementation on systemic microvascular function, in patients with HF New York Heart Association (NYHA) classes I/II. Cutaneous microvascular flow and reactivity were assessed using laser speckle contrast imaging, coupled with pharmacological local vasodilator stimuli. Fifteen patients (aged 64.5±6.2 years, 11 males) received WP supplementation and ten patients (aged 68.2±8.8 years, 8 males) received placebo (maltodextrin). The increase in endothelial-dependent microvascular vasodilation, induced by skin iontophoresis of acetylcholine, was improved after WP (P=0.03) but not placebo (P=0.37) supplementation. Moreover, endothelial-independent microvascular vasodilation induced by skin iontophoresis of sodium nitroprusside, was also enhanced after WP (P=0.04) but not placebo (P=0.42) supplementation. The results suggested that dietary supplementation with WP improved systemic microvascular function in patients with HF.     

Mechano-transduction to muscle protein synthesis is modulated by FAK

We examined the involvement of focal adhesion kinase (FAK) in mechano-regulated signalling to protein synthesis by combining muscle-targeted transgenesis with a physiological model for un- and reloading of hindlimbs. Transfections of mouse tibialis anterior muscle with a FAK expression construct increased FAK protein 1.6-fold versus empty transfection in the contralateral leg and elevated FAK concentration at the sarcolemma. Altered activation status of phosphotransfer enzymes and downstream translation factors showed that FAK overexpression was functionally important. FAK auto-phosphorylation on Y397 was enhanced between 1 and 6 h of reloading and preceded the activation of p70S6K after 24 h of reloading. Akt and translation initiation factors 4E-BP1 and 2A, which reside up- or downstream of p70S6K, respectively, showed no FAK-modulated regulation. The findings identify FAK as an upstream element of the mechano-sensory pathway of p70S6K activation whose Akt-independent regulation intervenes in control of muscle mass by mechanical stimuli in humans.