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.

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.

Resistance training with or without nutritional supplementation showed no influence on muscle thickness in old-institutionalized adults: a secondary analysis of the Vienna Active Ageing Study.

BACKGROUND: Resistance training and protein supplementation are recommended strategies to combat sarcopenia. AIM: Quantification of muscle thickness (MT) by musculoskeletal ultrasound is a promising method to follow changes in skeletal muscles. The aim of this study was to investigate the effect of six months of resistance training with or without nutritional supplementation on MT of M. quadriceps in institutionalized old adults. DESIGN: This is a prospective, randomized, multi-arm parallel and controlled intervention study. SETTING: This study was conducted in five different retirement care facilities. POPULATION: Institutionalized individuals (mean age 82.6±6.2 years) were randomly assigned to an elastic band resistance training (N.=41), training with nutritional supplementation (N.=36) or control group (N.=40). METHODS: Health status and handgrip strength were investigated at baseline. MT of all parts of M. quadriceps of the left leg was assessed using musculoskeletal ultrasound at baseline and after six months. Linear regression models adjusted for age, BMI and sex were calculated to investigate the influence of baseline characteristics on MT. Multivariable regression analyses were performed for investigation of study intervention on MT. Follow-up examinations were performed after 12 and 18 months. RESULTS: Handgrip strength of both hands was significantly correlated with MT of M. vastus lateralis. Moreover, the sum of regularly taken medication was significantly correlated to MT of all parts of quadriceps. Six months of training or nutritional supplementation was not able to alter MT. However, participants with lower baseline MT values or a higher number of diseases and medications at baseline showed significant higher increases in MT after intervention. CONCLUSIONS: Resistance training using elastic bands with or without nutritional supplementation did not alter MT of M. quadriceps of old institutionalized individuals. However, baseline values and health status had a significant influence on the training effect. CLINICAL REHABILITATION IMPACT: As old individuals are very heterogenic according to their health and muscle status; further studies might focus on individualizing training regimes with particular emphasize on accompanied diseases and medications of this population.

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.

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.

Circulating cell-free DNA, telomere length and bilirubin in the Vienna Active Ageing Study: exploratory analysis of a randomized, controlled trial.

Telomere length (TL) in blood cells is widely used in human studies as a molecular marker of ageing. Circulating cell-free DNA (cfDNA) as well as unconjugated bilirubin (UCB) are dynamic blood constituents whose involvement in age-associated diseases is largely unexplored. To our knowledge, there are no published studies integrating all three parameters, especially in individuals of advanced age. Here we present a secondary analysis from the Vienna Active Aging Study (VAAS), a randomized controlled intervention trial in institutionalized elderly individuals (n = 101). Using an exploratory approach we combine three blood-based molecular markers (TL, UCB and cfDNA) with a range of primary and secondary outcomes from the intervention. We further look at the changes occurring in these parameters after 6-month resistance exercise training with or without supplementation. A correlation between UCB and TL was evident at baseline (p < 0.05), and both were associated with increased chromosomal anomalies such as nucleoplasmatic bridges and nuclear buds (p < 0.05). Of the three main markers explored in this paper, only cfDNA decreased significantly (p < 0.05) after 6-month training and dietary intervention. No clear relationship could be established between cfDNA and either UCB or TL. The trial was registered at ClinicalTrials.gov (NCT01775111).