Nutritional supplementation alters associations between one-carbon metabolites and cardiometabolic risk profiles in older adults: a secondary analysis of the Vienna Active Ageing Study.

PURPOSE: Cardiovascular diseases and cognitive decline, predominant in ageing populations, share common features of dysregulated one-carbon (1C) and cardiometabolic homeostasis. However, few studies have addressed the impact of multifaceted lifestyle interventions in older adults that combine both nutritional supplementation and resistance training on the co-regulation of 1C metabolites and cardiometabolic markers. METHODS: 95 institutionalised older adults (83 ± 6 years, 88.4% female) were randomised to receive resistance training with or without nutritional supplementation (Fortifit), or cognitive training (control for socialisation) for 6 months. Fasting plasma 1C metabolite concentrations, analysed by liquid chromatography coupled with mass spectrometry, and cardiometabolic parameters were measured at baseline and the 3- and 6-month follow-ups. RESULTS: Regardless of the intervention group, choline was elevated after 3 months, while cysteine and methionine remained elevated after 6 months (mixed model time effects, p < 0.05). Elevated dimethylglycine and lower betaine concentrations were correlated with an unfavourable cardiometabolic profile at baseline (spearman correlations, p < 0.05). However, increasing choline and dimethylglycine concentrations were associated with improvements in lipid metabolism in those receiving supplementation (regression model interaction, p < 0.05). CONCLUSION: Choline metabolites, including choline, betaine and dimethylglycine, were central to the co-regulation of 1C metabolism and cardiometabolic health in older adults. Metabolites that indicate upregulated betaine-dependent homocysteine remethylation were elevated in those with the greatest cardiometabolic risk at baseline, but associated with improvements in lipid parameters following resistance training with nutritional supplementation. The relevance of how 1C metabolite status might be optimised to protect against cardiometabolic dysregulation requires further attention.

Muscle mass, strength and functional outcomes in critically ill patients after cardiothoracic surgery: does neuromuscular electrical stimulation help? The Catastim 2 randomized controlled trial.

BACKGROUND: The effects of neuromuscular electrical stimulation (NMES) in critically ill patients after cardiothoracic surgery are unknown. The objectives were to investigate whether NMES prevents loss of muscle layer thickness (MLT) and strength and to observe the time variation of MLT and strength from preoperative day to hospital discharge. METHODS: In this randomized controlled trial, 54 critically ill patients were randomized into four strata based on the SAPS II score. Patients were blinded to the intervention. In the intervention group, quadriceps muscles were electrically stimulated bilaterally from the first postoperative day until ICU discharge for a maximum of 14 days. In the control group, the electrodes were applied, but no electricity was delivered. The primary outcomes were MLT measured by ultrasonography and muscle strength evaluated with the Medical Research Council (MRC) scale. The secondary functional outcomes were average mobility level, FIM score, Timed Up and Go Test and SF-12 health survey. Additional variables of interest were grip strength and the relation between fluid balance and MLT. Linear mixed models were used to assess the effect of NMES on MLT, MRC score and grip strength. RESULTS: NMES had no significant effect on MLT. Patients in the NMES group regained muscle strength 4.5 times faster than patients in the control group. During the first three postoperative days, there was a positive correlation between change in MLT and cumulative fluid balance (r = 0.43, P = 0.01). At hospital discharge, all patients regained preoperative levels of muscle strength, but not of MLT. Patients did not regain their preoperative levels of average mobility (P = 0.04) and FIM score (P = 0.02) at hospital discharge, independent of group allocation. CONCLUSIONS: NMES had no effect on MLT, but was associated with a higher rate in regaining muscle strength during the ICU stay. Regression of intramuscular edema during the ICU stay interfered with measurement of changes in MLT. At hospital discharge patients had regained preoperative levels of muscle strength, but still showed residual functional disability and decreased MLT compared to pre-ICU levels in both groups. TRIAL REGISTRATION: Clinicaltrials.gov identifier NCT02391103. Registered on 7 March 2015.

Elastic band resistance training influences transforming growth factor-ß receptor I mRNA expression in peripheral mononuclear cells of institutionalised older adults: the Vienna Active Ageing Study (VAAS).

BACKGROUND: Ageing, inactivity and obesity are associated with chronic low-grade inflammation contributing to a variety of lifestyle-related diseases. Transforming growth factor-ß (TGF-ß) is a multimodal protein with various cellular functions ranging from tissue remodelling to the regulation of inflammation and immune functions. While it is generally accepted that aerobic exercise exerts beneficial effects on several aspects of immune functions, even in older adults, the effect of resistance training remains unclear. The aim of this study was to investigate whether progressive resistance training (6 months) with or without nutritional supplementation (protein and vitamins) would influence circulating C-reactive protein and TGF-ß levels as well as TGF-ß signalling in peripheral mononuclear cells (PBMCs) of institutionalised adults with a median age of 84.5 (65.0-97.4) years. RESULTS: Elastic band resistance training significantly improved performance as shown by the arm-lifting test (p = 0.007), chair stand test (p = 0.001) and 6-min walking test (p = 0.026). These results were paralleled by a reduction in TGF-ß receptor I (TGF-ßRI) mRNA expression in PBMCs (p = 0.006), while circulating inflammatory markers were unaffected. Protein and vitamin supplementation did not provoke any additional effects. Interestingly, muscular endurance of upper and lower body and aerobic performance at baseline were negatively associated with changes in circulating TGF-ß at the early phase of the study. Furthermore, drop-outs of the study were characterised not only by lower physical performance but also higher TGF-ß and TGF-ßRI mRNA expression, and lower miRNA-21 expression. CONCLUSIONS: Progressive resistance training with elastic bands did not influence chronic low-grade inflammation but potentially affected TGF-ß signalling in PBMCs through altered TGF-ßRI mRNA expression. There appears to be an association between physical performance and TGF-ß expression in PBMCs of older adults, in which the exact mechanisms need to be clarified.

Effects of elastic band resistance training and nutritional supplementation on muscle quality and circulating muscle growth and degradation factors of institutionalized elderly women: the Vienna Active Ageing Study (VAAS).

PURPOSE: Regular resistance exercise training and a balanced diet may counteract the age-related muscular decline on a molecular level. The aim of this study was to investigate the influence of elastic band resistance training and nutritional supplementation on circulating muscle growth and degradation factors, physical performance and muscle quality (MQ) of institutionalized elderly. METHODS: Within the Vienna Active Ageing Study, 91 women aged 83.6 (65.0-92.2) years were randomly assigned to one of the three intervention groups (RT, resistance training; RTS, resistance training plus nutritional supplementation; CT, cognitive training). Circulating levels of myostatin, activin A, follistatin, IGF-1 and GDF-15, as well as MQ and functional parameters were tested at baseline as well as after 3 and 6 months of intervention. RESULTS: MQ of lower extremities significantly increased in the RT group (+14 %) and RTS group (+12 %) after 6 months. Performance improved in the RT and RTS groups for chair stand test (RT: +18 %; RTS: +15 %). Follistatin increased only in the RT group (+18 %) in the latter phase of the intervention, accompanied by a decrease in the activin A-to-follistatin ratio (-7 %). IGF-1, myostatin and GDF-15 levels were not affected by the intervention. CONCLUSION: Our data confirm that strength training improves physical performance and MQ even in very old institutionalized women. This amelioration appears to be mediated by blocking muscle degradation pathways via follistatin rather than inducing muscle growth through the IGF-1 pathway. As plasma levels of biomarkers reflect an overall status of various organ systems, future studies of tissue levels are suggested.

The impact of six months strength training, nutritional supplementation or cognitive training on DNA damage in institutionalised elderly.

Aging and its aligned loss of muscle mass are associated with higher levels of DNA damage and deteriorated antioxidant defence. To improve the body's overall resistance against DNA damage, maintaining a healthy and active lifestyle is desirable, especially in the elderly. As people age, many have to change their residence from home living to an institution, which is often accompanied by malnutrition, depression and inactivity. The current study aimed at investigating the effect of a 6-month progressive resistance training (RT), with or without protein and vitamin supplementation (RTS), or cognitive training (CT), on DNA strand breaks in 105 Austrian institutionalised women and men (65-98 years). DNA damage was detected by performing the single cell gel electrophoresis (comet) assay. Physical fitness was assessed using the chair rise, the 6-min-walking and the handgrip strength test. In addition, antioxidant enzyme activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT) were analysed. Basal DNA damage (lysis) increased significantly after 3 months of intervention in the RT group (T1 - T2 + 20%, P = 0.001) and the RTS group (T1 - T2 + 17%, P = 0.002) and showed a similar tendency in the CT group (T1 - T2 + 21%, P = 0.059). %DNA in tail decreased in cells exposed to H2O2 significantly in the RT (T1 - T2 - 24%, P = 0.030; T1 - T3 - 18%, P = 0.019) and CT (T1 - T2 - 21%, P = 0.004; T1 - T3 - 13%, P = 0.038) groups. Only RT and RTS groups showed significant differences overtime in enzyme activity (RT + 22% CAT-activity T1 - T3, P = 0.013; RTS + 6% SOD-activity T2 - T3, P = 0.005). Contrary to the time effects, no difference between groups was detected for any parameter at any time point. Our results suggest that both CT and RT improve resistance against H2O2 induced DNA damage and that a nutritional supplement has no further protective effect in institutionalised elderly.

Influence of age and physical fitness on miRNA-21, TGF-ß and its receptors in leukocytes of healthy women.

The TGF-ß superfamily has been shown to play an important role in a wide range of physiological as well as pathological processes including ageing, immune modulation, atherosclerosis and cancer development. The aim of the current study was to investigate (i) whether TGF-ß signalling in peripheral blood mononuclear cells (PBMCs) would differ between young and old females and (ii) whether physical performance parameters of elderly women would be related to the expression of TGF-ß or its receptors. Sixteen healthy young (22-28 years; YF) and 90 healthy older (65-92 years; OF) females participated in the study. In addition to several components of health-related physical fitness, circulating CRP and TGF-ß levels were determined together with the mRNA expression of TGF-ß, TGF-ßRI, TGF-ßRII, and miRNA-21 (known to interfere with TGF-ß signalling) in PBMCs. Physical fitness as determined by 6-minutes walking test (YF:median 932 (range 573-1254) m; OF:360 (114-558) m), handgrip strength (YF: 32 (24-39) kg; OF:18(10-30) kg), relative isokinetic peak torque of knee extensors (YF:1.9 (1.2- 2.3) Nm/kg; OF:1.0 (0.2-1.9) Nm/kg and flexors (YF: 1.1 (0.7- 1.5) Nm/kg; OF: 0.5 (0.2-1.0) Nm/kg was substantially lower in older women (p<0.001 for all comparisons). These changes were paralleled by an increase in hs-CRP (YF: 0.9 (0.1-4.3)mg/L; OF: 2.3 (0.3-56.7)mg/L,p<0.001). Serum levels of TGF-ß and TGF-ß mRNA levels from PBMCs did not differ between young and old women whereas, both TGF- ßRI/GAPDH (YF: 4.07 (1.38-14.60); OF: 2.08 (0.14-28.81); p=0.020) and TGF-ßRII/GAPDH levels (YF: 3.16 (1.14- 10.25); OF: 1.71 (0.51-14.86); p=0.020) were lower with respect to old age. In elderly women, only TGF-ßRΙ expression correlated negatively with miRNA-21 expression in PBMCs (ρ=-0.315; p=0.004). Interestingly, hs-CRP and miRNA correlated positively with handgrip strength (ρ=0.237 and ρ=243, p<0.05), while none of the TGF-ß-related parameters were related to physical performance. The results suggest that age affects TGF-ß signalling in leukocytes by altering the expression levels of its receptors. These changes seem to occur independently of physical fitness of old women.

The influence of age and aerobic fitness on chromosomal damage in Austrian institutionalised elderly.

Ageing goes hand in hand with altered DNA repair and defence mechanisms against DNA damage. To improve the body's overall resistance against chromosomal damage, maintaining a healthy and active lifestyle is of great concern, especially in the elderly. As more and more people are getting older, they change from home living to an institutionalised situation, which is often accompanied by malnutrition, depression and inactivity. So far, there is a lack of data on chromosomal damage in relation to age and fitness status. The aim of this study was to examine the effect of age and aerobic fitness on endpoints of DNA damage in 105 institutionalised women and men (65-98 years) living in Vienna. Chromosomal damage was measured by conducting the cytokinesis block micronucleus cytome assay. Aerobic fitness of the participants was assessed using the 6-min walking test. To investigate the effect of age on micronuclei (MN) frequency and evaluate the particular age group, our data were merged with data from a recent study by Wallner et al. (Effects of unconjugated bilirubin on chromosomal damage in individuals with Gilbert's syndrome measured with the micronucleus cytome assay. Mutagenesis 2012; 27: 731-735). Age and MN frequency correlated significantly for squared regression (r = 0.577; P = 0.000) and showed a levelling-off at ~60 years of age. Furthermore, we observed a significant negative linear correlation (r = -0.222; P = 0.03) between MN frequency and 6-min walking performance. There was a plateau-like effect of the MN frequency above the age of 60-70 years, indicating a higher resistance against chromosomal damage of the 'survivors' of the regular lifespan. This study suggests that aerobic fitness 'protects' against chromosomal damage at high age.

Association of Bioelectrical Impedance Phase Angle with Physical Performance and Nutrient Intake of Older Adults.

In recent years, the phase angle (PhA) as a raw bioelectrical impedance analysis variable has gained attention to assess cell integrity and its association to physical performance in either sports-related or clinical settings. However, data on healthy older adults are scarce. Therefore, data on body composition, physical performance and macronutrient intake from older adults (n = 326, 59.2% women, 75.2 ± 7.2 years) were retrospectively analyzed. Physical performance was evaluated by the Senior Fitness Test battery, gait speed, timed up and go and handgrip strength. Body composition was determined by the BIA and dual-energy X-ray absorptiometry (from a subgroup of n = 51). The PhA was negatively associated with the timed up and go test and age (r = -0.312 and -0.537, p < 0.001), and positively associated with the 6 min walk test, 30 s chair stand, handgrip strength, gait speed and physical performance score (r = 0.170-0.554, p < 0.05), but not protein intake (r = 0.050, p = 0.386). Hierarchical multiple regression analysis showed that especially age, sex, BMI, but also the PhA predicted the performance test outcomes. In conclusion, the PhA seems to be an interesting contributor to physical performance, but sex- and age-specific norm values still need to be determined.

The influence of vitamin D supplementation and strength training on health biomarkers and chromosomal damage in community-dwelling older adults.

Older adults lack of proper physical activity which is often accompanied by vitamin D deficiency. Those factors are known to contribute to health issues in the later years of life. The main goal of this intervention study was to investigate the effect of different vitamin D supplementation strategies for 4 weeks solely or combined with a 10-week strength training program on chromosomal stability in peripheral blood mononuclear cells in community-dwelling older people. One hundred women and men (65-85 years) received either vitamin D3 daily (800 IU), a monthly dose (50.000 IU) or placebo for 17 weeks. All groups received 400 mg calcium daily. The fitness status of the study participants was measured using the 30- second chair stand test, the handgrip strength test and the 6-min walk test. The cytokinesis block micronucleus cytome (CBMN) assay was applied to analyze chromosomal anomalies, including cytotoxic and genotoxic parameters. Changes in antioxidant markers were measured in plasma. Walking distance and chair stand performance improved significantly. Increased levels of the parameters of the CBMN assay were detected for all intervention groups at study end. At baseline micronuclei (MNi) frequency correlated significantly with BMI in both sexes (females: r = 0.369, p = 0.034; males: r = 0.265, p = 0.035), but not with vitamin D serum levels. In females, body fat (r = 0.372, p < 0.001) and functional parameter using the 30-s chair stand test (r = 0.311, p = 0.002) correlated significantly with MNi frequency. Interestingly, not vitamin D supplementation but 10 weeks of resistance training increased MNi frequency indicating elevated chromosomal instability and also adverse effects on antioxidant markers including glutathione and FRAP were detected in the group of community-dwelling older adults.

Effects of an increased habitual dietary protein intake followed by resistance training on fitness, muscle quality and body composition of seniors: A randomised controlled trial.

BACKGROUND & AIMS: Resistance training and a sufficient amount of dietary protein have been suggested to build up and maintain muscle mass, strength and function into old age. As there is still no consensus on the optimum amount of protein intake in older people, this study aims to evaluate first whether it is achievable to double the recommended amount, which is 1 g/kg BW/d in German speaking countries, via food administration and secondly whether this would lead to stronger improvements when subsequently combined with resistance training. METHODS: In total, 136 community-dwelling older adults (54% females, 72.9 ± 4.8 yrs) were randomly assigned to one of the three study groups: observational control (CON), recommended protein (RP + T) and high protein (HP + T) intake groups. After six weeks of observation or nutritional counselling to achieve the respective protein target levels, eight weeks of resistance training (2x/week) were applied in RP + T and HP + T groups. Parameters indicative for muscle mass, strength and function were measured at baseline (t1), before (t2) and after the training period (t3). RESULTS: Baseline protein intake for the different groups were 0.83 (CON), 0.97 (RP + T) and 0.78 (HP + T) g/kg BW/d and increased by 0.18 ± 0.31 (RP + T, p = 0.003) and 0.83 ± 0.33 (HP + T, p > 0.001) g/kg BW/d between t1 and t3 while CON remained unchanged. Most of the physical performance parameters improved over time, but no interaction effects between group and time could be observed. While body fat mass initially increased from t1 to t2 (0.8 ± 2.3 kg, p = 0.001), skeletal muscle mass decreased (-0.5 ± 1.9 kg, p = 0.025), a trend which was reversed from t2 to t3 only in HP + T group (body fat mass: -0.47 ± 2.12 kg, p = 0.041; muscle mass: 0.51 ± 1.57 kg, p = 0.021). CONCLUSION: The findings suggest that a substantial increase of habitual protein intake above the currently recommended levels is achievable within 17 weeks in community-dwelling older adults, whereby the extra amount of protein led to minor changes in body composition but not physical performance or muscle quality (NCT04023513).

The plasma proteome is favorably modified by a high protein diet but not by additional resistance training in older adults: A 17-week randomized controlled trial.

Background: The age-related loss of muscle mass significantly contributes to the development of chronic diseases, loss of mobility and dependency on others, yet could be improved by an optimized lifestyle. Objective: The goal of this randomized controlled trial was to compare the influence of a habitual diet (CON) with either a diet containing the recommended protein intake (RP) or a high protein intake (HP), both with and without strength training, on the plasma proteome in older adults. Methods: One hundred and thirty-six women and men (65-85 years) were randomly assigned to three intervention groups. CON continued their habitual diet; participants of the HP and RP group consumed either high protein or standard foods. After 6 weeks of dietary intervention, HP and RP groups additionally started a strength training intervention twice per week for 8 weeks. Twenty-four hours dietary recalls were performed every 7-10 days. Body composition was assessed and blood taken. Plasma proteomics were assessed with LC-MS. Results: Participants of the HP group doubled their baseline protein intake from 0.80 ± 0.31 to 1.63 ± 0.36 g/kg BW/d; RP increased protein intake from 0.89 ± 0.28 to 1.06 ± 0.26 g/kg BW/d. The CON group kept the protein intake stable throughout the study. Combined exercise and HP initiated notable changes, resulting in a reduction in bodyfat and increased muscle mass. Proteomics analyses revealed 14 significantly affected proteins by HP diet, regulating innate immune system, lipid transport and blood coagulation, yet the additional strength training did not elicit further changes. Conclusions: Combined HP and resistance exercise in healthy older adults seem to induce favorable changes in the body composition. Changes in the plasma proteome due to the high protein diet point to a beneficial impact for the innate immune system, lipid transport and blood coagulation system, all of which are involved in chronic disease development. Clinical trial registration: The study was registered at ClinicalTrials.gov (NCT04023513).

Effects of Vitamin D3 Supplementation and Resistance Training on 25-Hydroxyvitamin D Status and Functional Performance of Older Adults: A Randomized Placebo-Controlled Trial.

Vitamin D status is associated with muscle strength and performance in older adults. To examine the additive effects of vitamin D3 supplementation during resistance training, 100 seniors (65-85 years) participated in a 16-week intervention. Besides a daily dose of 400 mg of calcium, participants received either 800 IU vitamin D3 per day (VDD), 50,000 IU vitamin D3 per month (VDM) or nothing (CON). After the initial loading phase of four weeks, all groups started a 10-week resistance training program. Assessments of 25-hydroxyvitamin D (25(OH)D) status, muscle strength endurance (30-s chair stand and arm curl tests), aerobic capacity (6-min walk test) and functional mobility (gait speed and timed up and go test) were undertaken at baseline, after four weeks and at the end of the study. 25(OH)D status significantly improved in VDD and VDM, but not in CON (time x group: p = 0.021), as 15.2% of CON, 40.0% of VDD and 61.1% of VDM reached vitamin D sufficiency (>30 ng/mL; p = 0.004). Chair stand test, arm curl test, 6-min walk test, gait speed and timed up and go test improved over the whole intervention period (p < 0.05), however only chair stand and arm curl test were selectively affected by resistance training (p < 0.001). Neither muscle strength endurance, nor functional mobility or aerobic capacity were modulated by vitamin D supplementation. Therefore, the mere amelioration of 25(OH)D status of older adults does not lead to an additive effect on muscular performance during RT.

The Effect of Elevated Protein Intake on DNA Damage in Older People: Comparative Secondary Analysis of Two Randomized Controlled Trials.

A high protein intake at old age is important for muscle protein synthesis, however, this could also trigger protein oxidation with the potential risk for DNA damage. The aim of this study was to investigate whether an increased protein intake at recommended level or well above would affect DNA damage or change levels of reduced (GSH) and oxidised glutathione (GSSG) in community-dwelling elderly subjects. These analyses were performed in two randomized intervention studies, in Austria and in New Zealand. In both randomized control trials, the mean protein intake was increased with whole foods, in the New Zealand study (n = 29 males, 74.2 ± 3.6 years) to 1.7 g/kg body weight/d (10 weeks intervention; p < 0.001)) in the Austrian study (n = 119 males and females, 72.9 ± 4.8 years) to 1.54 g/kg body weight/d (6 weeks intervention; p < 0.001)). In both studies, single and double strand breaks and as formamidopyrimidine-DNA glycosylase-sensitive sites were investigated in peripheral blood mononuclear cells or whole blood. Further, resistance to H2O2 induced DNA damage, GSH, GSSG and CRP were measured. Increased dietary protein intake did not impact on DNA damage markers and GSH/GSSG levels. A seasonal-based time effect (p < 0.05), which led to a decrease in DNA damage and GSH was observed in the Austrian study. Therefore, increasing the protein intake to more than 20% of the total energy intake in community-dwelling seniors in Austria and New Zealand did not increase measures of DNA damage, change glutathione status or elevate plasma CRP.

Chromosomal stability in buccal cells was linked to age but not affected by exercise and nutrients - Vienna Active Ageing Study (VAAS), a randomized controlled trial.

The purpose of this study was to investigate the effect of six months strength training with or without supplementing protein and vitamins, on chromosomal integrity of buccal cells in institutionalized elderly. One hundred seventeen women and men (65-98 years) performed either resistance training (RT), RT combined with a nutritional supplement (RTS) or cognitive training (CT) twice per week for six months. Participants' fitness was measured using the 6 min walking, the chair rise, and the handgrip strength test. Genotoxicity and cytotoxicity parameters were investigated with the Buccal Micronucleus Cytome (BMcyt) assay. Six minutes walking and chair rise performance improved significantly, however, no changes of the parameters of the BMcyt were detected. Age and micronuclei (MN) frequency correlated significantly, for both women (r = 0.597, p = 0.000) and men (r = 0.508, p = 0.000). Squared regressions revealed a significant increase in the MN frequency of buccal cells with age (R2 = 0.466, p = 0.000). Interestingly and contrary to what was shown in blood lymphocytes, chromosomal damage in buccal cells increases until very old age, which might qualify them as a valid biomarker for aging. Unexpectedly, in this group of institutionalized elderly, resistance training using elastic bands had no effect on chromosomal damage in buccal cells.

Neuromuscular electrical stimulation reduces skeletal muscle protein degradation and stimulates insulin-like growth factors in an age- and current-dependent manner: a randomized, controlled clinical trial in major abdominal surgical patients.

OBJECTIVE: To investigate the effect of neuromuscular electrical stimulation (NMES) on skeletal muscle metabolism after major abdominal surgery. SUMMARY BACKGROUND DATA: Protein catabolism associated with surgical interventions leads to reduced muscle strength, increased clinical complications and prolonged convalescence. Immobilization is suggested as a major stimulus for muscle wasting. This study investigates the potency of NMES on skeletal muscle growth factors and degradation processes in surgical patients. METHODS: This observer blind study included 26 patients after major abdominal surgery mainly due to cancer aged 60 +/- 10 years. Starting on the first postoperative day, 1 randomly assigned thigh of each patient was treated on 4 consecutive days with NMES, whereas the other leg was used as sham-stimulated control. Thereafter, muscle biopsies from both legs were performed. Differences in mRNA level, protein expression, and enzyme activity between legs were analyzed by cross-over analysis of variance (Clinical Trial Registration Number: NCT00635440). RESULTS: NMES significantly increased total RNA content and total sarcoplasmatic protein content. NMES significantly reduced ubiquitin-conjugated sarcoplasmatic proteins and proteasome activity. The mechano growth factor mRNA level correlated positively with the applied current and negatively with the body mass index of the patients. The increase in insulin like growth factor-1Ea mRNA after NMES correlated negatively with the age of the patients. CONCLUSIONS: This study shows that NMES significantly increases total RNA content and reduces protein degradation in postoperative patients. Moreover, the induction of growth factors by NMES reveals dependency on body mass index, age, and applied current. We conclude that NMES is a useful clinical tool to reduce protein catabolism in postoperative patients.

Effects of acute resistance exercise on proteolytic and myogenic markers in skeletal muscles of former weightlifters and age-matched sedentary controls.

BACKGROUND: Former athletes who continue a regular, performance-oriented training throughout life provide a unique model for studying successful aging. With this in mind, the current study aimed to compare the effects of an acute resistance exercise on proteolytic and myogenic markers in older weightlifters and untrained participants. METHODS: Sixteen older men (8 former weightlifters, 8 age-matched untrained controls) with an age of 61.2±8.2 years volunteered to participate in the study. Two days after assessing 1-RM, an acute exercise protocol (3 sets, 70-75% of one-repetition maximum until voluntary fatigue) was applied unilaterally on the dominant leg while the other leg served as control. Three hours after termination of the exercise, skeletal muscle tissue was obtained from m. vastus lateralis of both legs. RESULTS: Acute resistance exercise led to an up-regulation (>1.5-fold) of 14 genes in controls and of 13 genes in weightlifters. The transcription factors FOS and early growth response 1 (EGR1), as well as the E3 protein ligase TRIM63 comprised the most responsive genes to resistance exercise (EGR1:15.7-fold increase, P=0.003, FOS: 36.3-fold increase, P<0.001; TRIM63: 2.9-fold increase, P<0.001). In addition, myostatin levels were decreased in the exercised leg (0.6-fold, P<0.001). FOXO3 gene expression was significantly higher in weightlifters than in untrained controls (1.5-fold, P=0.042). CONCLUSIONS: Trained and untrained older adults respond to an acute bout of resistance exercise in a very similar way irrespective of training status, although some differences exist in FOXO3, potentially reflecting the superior capacity of trained persons in regulating cellular homeostasis.

Fat Soluble Vitamins in Institutionalized Elderly and the Effect of Exercise, Nutrition and Cognitive Training on Their Status-The Vienna Active Aging Study (VAAS): A Randomized Controlled Trial.

BACKGROUND: Institutionalized elderly are at higher risk for micronutrient deficiency. In particular, fat soluble micronutrients, which additionally have antioxidative function, are of interest. The purpose of this secondary investigation of the Vienna Active Ageing Study was to assess and evaluate the plasma status of retinol, alpha- and gamma-tocopherol, alpha- and beta-carotene, lutein, zeaxanthin, beta-cryptoxanthin, and lycopene, as well as vitamin D (25(OH)D) in a cohort of institutionalized elderly. We further determined the effect of six months strength training with or without supplementing (antioxidant) vitamins and protein on the plasma status of these ten micronutrients. METHODS: Three groups (n = 117, age = 83.1 ± 6.1 years)-resistance training (RT), RT combined with protein and vitamin supplementation (RTS), or cognitive training (CT)-performed two guided training sessions per week for six months. Micronutrients were measured with High Performance Liquid Chromatography (HPLC) at baseline and after 6 months of intervention. Physical fitness was assessed by the 6-min-walking, the 30-s chair rise, isokinetic dynamometry, and the handgrip strength tests. RESULTS: At baseline, the plasma status of retinol was satisfactory, for alpha-tocopherol, beta-carotene, and 25(OH)D, the percentage of individuals with an insufficient status was 33%, 73% and 61%/81% (when using 50 nmol/L or 75 nmol/L as threshold levels for 25(OH)D), respectively. Plasma analyses were supported by intake data. Six months of elastic band resistance training with or without protein-vitamin supplementation had no biological impact on the status of fat soluble micronutrients. Even for vitamin D, which was part of the nutritional supplement (additional 20 µg/d), the plasma status did not increase significantly, however it contributed to a lower percentage of elderly below the threshold levels of 50/75 nmol/L (49%/74%). CONCLUSIONS: The findings of the study lead to the strong recommendation for regular physical activity and increased consumption of plant-based foods in institutionalized elderly. When supported by blood analysis, supplementing micronutrients in a moderate range should also be considered.

Age and the effect of exercise, nutrition and cognitive training on oxidative stress - The Vienna Active Aging Study (VAAS), a randomized controlled trial.

The purpose of this study was to investigated the effect of age - over or under life-expectancy (LE) - on six months resistance training alone or combined with a nutritional supplement, and cognitive training by analyzing markers for oxidative stress and antioxidant defense in institutionalized elderly, living in Vienna. Three groups (n = 117, age = 83.1 ±â€¯6.1 years) - resistance training (RT), RT combined with protein and vitamin supplementation (RTS) or cognitive training (CT) - performed two guided training sessions per week for six months. Oxidative stress, antioxidant defense and DNA strand breaks were analyzed and transformed into an "antioxidant factor" to compare the total effect of the intervention. Physical fitness was assessed by the 6-min-walking, the chair-rise and the handgrip strength tests. We observed significant negative baseline correlations between 8-oxo-7.8-dihydroguanosine and handgrip strength (r = -0.350, p = 0.001), and between high sensitive troponin-T and the 6-min-walking test (r = -0.210, p = 0.035). RT and RTS groups, showed significant improvements in physical performance. Over LE, subjects of the RT group demonstrated a significant greater response in the "antioxidant factor" compared to RTS and CT (RT vs. RTS p = 0.033, RT vs. CT p = 0.028), whereas no difference was observed between the intervention groups under LE. Six months of elastic band resistance training lead to improvements in antioxidant defense, DNA stability and oxidative damage, summarized in the "antioxidant factor", however mainly in subjects over their statistical LE. Consuming a supplement containing antioxidants might inhibit optimal cellular response to exercise. The study was approved by the ethics committee of the City of Vienna (EK-11-151-0811) and registered at ClinicalTrials.gov, NCT01775111.

Strength training increases skeletal muscle quality but not muscle mass in old institutionalized adults: a randomized, multi-arm parallel and controlled intervention study.

BACKGROUND: Age related loss of skeletal muscle mass is accompanied by changes in muscle quality leading to impairment of functional status. AIM: This study investigated the effect of resistance training and nutritional supply on muscle mass and muscle quality in very old institutionalized adults. DESIGN: Prospective, randomized, multi-arm parallel and controlled intervention study. SETTING: This study was conducted in five retirement care facilities. POPULATION: This subgroup of the Vienna Active Ageing Study included 54 women and men (82.4±6.0 years) with impaired health status. Participants were randomly assigned either to elastic band resistance training (N.=16), training with nutritional supplementation (N.=21) or control group (N.=17). METHODS: Health status was assessed at baseline with functional tests, cognitive status, nutritional status, sum of medications as well as sum of diseases. Skeletal muscle mass, determined by dual-energy X-ray absorptiometry, isokinetic knee extension and flexion force and handgrip strength were assessed at baseline and after 6 months. Muscle quality of lower extremities was defined as ratio of the extensor (MQ_LE (Ext.)) or flexor strength (MQ_LE (Flex.)) to lean leg mass. Muscle quality of upper extremity was defined as ratio of handgrip strength to lean arm mass. Follow-up examinations were performed after 12 and 18 months of intervention. RESULTS: Muscle quality, but not muscle mass, showed significant correlations to functional tests at baseline (0.300 - 0.614, P<0.05). Resistance training significantly enhanced muscle quality of lower extremity after 6 months (MQ_LE (Ext.) +19.8%, MQ_LE (Flex.) +30.8%, P<0.05). Nutritional supplementation could not further increase the training effect. Participants with lower muscle quality at baseline benefit most from the training intervention. Skeletal muscle mass was not changed by any intervention. CONCLUSIONS: Resistance training with elastic bands improved muscle quality in very old people. Additional nutritional supplementation was not able to further improve the effects obtained by training alone. CLINICAL REHABILITATION IMPACT: Elastic band resistance training could be safely used to improve muscle quality even in old people with impaired health status. Weak and chronically ill participants benefit most from this training.

[Cellular regulation of anabolism and catabolism in skeletal muscle during immobilisation, aging and critical illness]. / Zelluläre Regulation des Anabolismus und Katabolismus der Skelettmuskulatur bei Immobilität, im Alter und bei kritisch Kranken.

Skeletal muscle atrophy is associated with situations of acute and chronical illness, such as sepsis, surgery, trauma and immobility. Additionally, it is a common problem during the physiological process of aging. The myofibrillar proteins myosin and actin, which are essential for muscle contraction, are the major targets during the process of protein degradation. This leads to a general loss of muscle mass, muscle strength and to increased muscle fatigue. In critically ill or immobile patients skeletal muscle atrophy is accompanied by enhanced inflammation, reduced wound healing, weaning complications and difficulties in mobilisation. During aging it results in falls, fractures, physical injuries and loss of mobility. Relating to the primary stimulators - hormones, muscle lengthening, stress, inflammation, neuronal activity - research is now focusing on the investigation of the signal transduction pathways, which influence protein synthesis and protein degradation during skeletal muscle atrophy.