Higher habitual dietary flavonoid intake associates with lower central blood pressure and arterial stiffness in healthy older adults.

Flavonoids have shown anti-hypertensive and anti-atherosclerotic properties: the impact of habitual flavonoid intake on vascular function, central haemodynamics and arterial stiffness may be important. We investigated the relationship between habitual flavonoid consumption and measures of central blood pressure and arterial stiffness. We performed cross-sectional analysis of 381 non-smoking healthy older adults (mean age 66·0 (sd 4·1) years; BMI, 26·4 (sd 4·41) kg/m2; 41 % male) recruited as part of the Australian Research Council Longevity Intervention study. Flavonoid intake (i.e. flavonols, flavones, flavanones, anthocyanins, isoflavones, flavan-3-ol monomers, proanthocyanidins, theaflavins/thearubigins and total consumption) was estimated from FFQ using the US Department of Agriculture food composition databases. Measures of central haemodynamics and arterial stiffness included systolic blood pressure (cSBP), diastolic blood pressure (cDBP), mean arterial pressure (cMAP) and augmentation index (cAIx). After adjusting for demographic and lifestyle confounders, each sd/d higher intake of anthocyanins ((sd 44·3) mg/d) was associated with significantly lower cDBP (-1·56 mmHg, 95 % CI -2·65, -0·48) and cMAP (-1·62 mmHg, 95 % CI -2·82, -0·41). Similarly, each sd/d higher intake of flavanones ((sd 19·5) mg/d) was associated with ~1 % lower cAIx (-0·93 %, 95 % CI -1·77, -0·09). These associations remained significant after additional adjustment for (1) a dietary quality score and (2) other major nutrients that may affect blood pressure or arterial stiffness (i.e. Na, K, Ca, Mg, n-3, total protein and fibre). This study suggests a possible benefit of dietary anthocyanin and flavanone intake on central haemodynamics and arterial stiffness; these findings require corroboration in further research.

High intensity exercise downregulates FTO mRNA expression during the early stages of recovery in young males and females.

BACKGROUND: Physical exercise and activity status may modify the effect of the fat mass- and obesity-associated (FTO) genotype on body weight and obesity risk. To understand the interaction between FTO's effect and physical activity, the present study investigated the effects of high and low intensity exercise on FTO mRNA and protein expression, and potential modifiers of exercise-induced changes in FTO in healthy-weighted individuals. METHODS: Twenty-eight untrained males and females (25.4 ± 1.1 years; 73.1 ± 2.0 kg; 178.8 ± 1.4 cm; 39.0 ± 1.2 ml.kg.min- 1 VO2peak) were genotyped for the FTO rs9939609 (T > A) polymorphism and performed isocaloric (400 kcal) cycle ergometer exercise on two separate occasions at different intensities: 80% (High Intensity (HI)) and 40% (Low Intensity (LO)) VO2peak. Skeletal muscle biopsies (vastus lateralis) and blood samples were taken pre-exercise and following 10 and 90 mins passive recovery. RESULTS: FTO mRNA expression was significantly decreased after HI intensity exercise (p = 0.003). No differences in basal and post-exercise FTO protein expression were evident between FTO genotypes. Phosphorylated adenosine monophosphate-activated protein kinase (AMPK) and Akt substrate of 160 kDa (AS160) were significantly increased following HI intensity exercise (p < 0.05). Multivariate models of metabolomic data (orthogonal two partial least squares discriminant analysis (O2PLS-DA)) were unable to detect any significant metabolic differences between genotypes with either exercise trial (p > 0.05). However, skeletal muscle glucose accumulation at 10 mins following HI (p = 0.021) and LO (p = 0.033) intensity exercise was greater in AA genotypes compared to TT genotypes. CONCLUSION: Our novel data provides preliminary evidence regarding the effects of exercise on FTO expression in skeletal muscle. Specifically, high intensity exercise downregulates expression of FTO mRNA and suggests that in addition to nutritional regulation, FTO could also be regulated by exercise. TRIAL REGISTRATION: ACTRN12612001230842. Registered 21 November 2012 - Prospectively registered, https://www.anzctr.org.au/.

Defects in mitochondrial ATP synthesis in dystrophin-deficient mdx skeletal muscles may be caused by complex I insufficiency.

Duchenne Muscular Dystrophy is a chronic, progressive and ultimately fatal skeletal muscle wasting disease characterised by sarcolemmal fragility and intracellular Ca2+ dysregulation secondary to the absence of dystrophin. Mounting literature also suggests that the dysfunction of key energy systems within the muscle may contribute to pathological muscle wasting by reducing ATP availability to Ca2+ regulation and fibre regeneration. No study to date has biochemically quantified and contrasted mitochondrial ATP production capacity by dystrophic mitochondria isolated from their pathophysiological environment such to determine whether mitochondria are indeed capable of meeting this heightened cellular ATP demand, or examined the effects of an increasing extramitochondrial Ca2+ environment. Using isolated mitochondria from the diaphragm and tibialis anterior of 12 week-old dystrophin-deficient mdx and healthy control mice (C57BL10/ScSn) we have demonstrated severely depressed Complex I-mediated mitochondrial ATP production rate in mdx mitochondria that occurs irrespective of the macronutrient-derivative substrate combination fed into the Kreb's cycle, and, which is partially, but significantly, ameliorated by inhibition of Complex I with rotenone and stimulation of Complex II-mediated ATP-production with succinate. There was no difference in the MAPR response of mdx mitochondria to increasing extramitochondrial Ca2+ load in comparison to controls, and 400 nM extramitochondrial Ca2+ was generally shown to be inhibitory to MAPR in both groups. Our data suggests that DMD pathology is exacerbated by a Complex I deficiency, which may contribute in part to the severe reductions in ATP production previously observed in dystrophic skeletal muscle.

Effects of G-trainer, cycle ergometry, and stretching on physiological and psychological recovery from endurance exercise.

The purpose of this study was to compare the effectiveness of 3 treatment modes (Anti-Gravity Treadmill [G-trainer], stationary cycling [CompuTrainer], and static stretching) on the physiological and psychological recovery after an acute bout of exhaustive exercise. In a crossover design, 12 aerobically trained men (21.3 ± 2.3 years, 72.1 ± 8.1 kg, 178.4 ± 6.3 cm, (Equation is included in full-text article.): 53.7 ± 6.3 ml·kg·min) completed a 29-km stationary cycling time trial. Immediately after the time trial, subjects completed 30 minutes of G-trainer or CompuTrainer (40% (Equation is included in full-text article.)) or static stretching exercises. A significant time effect was detected for plasma lactate (p = 0.010) and serum cortisol (p = 0.039) after exercise. No treatment or treatment by time interaction was identified for lactate or cortisol, respectively. No main effects for time, treatment, or treatment by time interaction were identified for interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α). No differences were observed among treatments in skeletal muscle peak power output, mean power output, time to peak power, and rate to fatigue at 24 hours postexercise bout. Finally, no significant changes in mood status were observed after exercise and between treatment groups. When compared with stationary cycling and static stretching, exercise recovery performed on the G-trainer was unable to reduce systemic markers of stress and inflammation, blood lactate, or improve anaerobic performance and psychological mood states after an exhaustive bout of endurance exercise. Further research is warranted that includes individualized recovery modalities to create balances between the stresses of training and competition.

Creatine supplementation post-exercise does not enhance training-induced adaptations in middle to older aged males.

PURPOSE: The present study evaluated the effects of creatine monohydrate (CrM) consumption post-exercise on body composition and muscle strength in middle to older males following a 12-week resistance training program. METHODS: In a double-blind, randomized trial, 20 males aged between 55 and 70 years were randomly assigned to consume either CrM-carbohydrate (CHO) [20 g days(-1) CrM + 5 g days(-1) CHO × 7 days, then 0.1 g kg(-1) CrM + 5 g CHO on training days (average dosage of ~8.8 g)] or placebo CHO (20 g days(-1) CHO × 7 days, then 5 g CHO on training days) while participating in a high intensity resistance training program [3 sets × 10 repetitions at 75% of 1 repetition maximum (1RM)], 3 days weeks(-1) for 12 weeks. Following the initial 7-day "loading" phase, participants were instructed to ingest their supplement within 60 min post-exercise. Body composition and muscle strength measurements, blood collection and vastus lateralis muscle biopsy were completed at 0, 4, 8 and 12 weeks of the supplement and resistance training program. RESULTS: A significant time effect was observed for 1RM bench press (p = 0.016), leg press (p = 0.012), body mass (p = 0.03), fat-free mass (p = 0.005) and total myofibrillar protein (p = 0.005). A trend for larger muscle fiber cross-sectional area in the type II fibers compared to type I fibers was observed following the 12-week resistance training (p = 0.08). No supplement interaction effects were observed. CONCLUSION: Post-exercise ingestion of creatine monohydrate does not provide greater enhancement of body composition and muscle strength compared to resistance training alone in middle to older males.

Optimizing the benefits of exercise on physical function in older adults.

As the number of older adults continues to rise worldwide, the prevention of physical disability among seniors is an increasingly important public health priority. Physical exercise is among the best known methods of preventing disability, but accumulating evidence indicates that considerable variability exists in the responsiveness of older adults to standard training regimens. Accordingly, a need exists to develop tailored interventions to optimize the beneficial effects of exercise on the physical function of older adults at risk for becoming disabled. The present review summarizes the available literature related to the use of adjuvant or alternative strategies intended to enhance the efficacy of exercise in improving the physical function of older adults. Within this work, we also discuss potential future research directions in this area.

Differential gene expression of FoxO1, ID1, and ID3 between young and older men and associations with muscle mass and function.

BACKGROUND AND AIMS: Aging is associated with significant losses of skeletal muscle mass and function. Numerous biochemical molecules have been implicated in the development of these age-related changes, however evidence from human models is sparse. Assessment of transcript expression is useful as it requires minimal tissue and may potentially be used in clinical trials. This study aimed to compare mRNA expression of proteolytic genes in skeletal muscle of young (18-35 yrs) and older (55-75 yrs) men. METHODS: Muscle tissue was obtained from young (n=14, 21.35±1.03 yrs) and older (n=13, 63.85±1.83 yrs) men using percutaneous biopsy, and transcript expression was quantified using real-time polymerase chain reaction. Lower limb muscle mass was assessed using DEXA while concentric peak torque (PT) and power were assessed via isokinetic dynamometer. When age-related differences in mRNA expression were observed, Pearson correlation coefficients were obtained to examine the relationship of transcripts to muscle mass and function. RESULTS: Older muscle contained significantly more transcript for Forkhead Box O 1 (FoxO1, p=0.001), Inhibitor of DNA binding 1 (ID1, p=0.009), and Inhibitor of DNA Binding 3 (ID3, p=0.043) than young muscle. FoxO1 was significantly correlated with lean mass (R=-0.44, p=0.023) and PT (R=-0.40, p=0.046) while ID3 was significantly correlated with PT (R=-0.58, p=0.001) and power (R=-0.65, p<0.001). Moreover, ID1 was significantly correlated with all assessed measures of muscle function - mass (R=-0.39, p=0.046), PT (R=-0.53, p=0.005), and power (R=-0.520, p=0.005). CONCLUSION: These data suggest that FoxO1, ID1, and ID3 are potentially useful as clinical biomarkers of age-related muscle atrophy and dysfunction.

Soy and the exercise-induced inflammatory response in postmenopausal women.

Aging is associated with increasing inflammation and oxidative stress in the body, both of which can have negative health effects. Successful attenuation of such processes with dietary countermeasures has major public health implications. Soy foods, as a source of high-quality protein and isoflavones, may improve such indices, although the effects in healthy postmenopausal women are not well delineated. A single-blind, randomized controlled trial was conducted in 31 postmenopausal women who were assigned to consume 3 servings of soy (n = 16) or dairy (n = 15) milk per day for 4 weeks. Parameters of systemic inflammation (tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), and interleukin-6 (IL-6)) and the oxidative defense system (superoxide dismutase (SOD), glutathione peroxidase, cyclooxygenase-2) were measured post supplementation, before and after an eccentric exercise bout performed to elicit an inflammatory response. A significant group-by-time effect for plasma TNF-alpha was observed (p = 0.02), with values in the dairy group increased post supplementation and then decreasing into the postexercise period. Additionally, significant time effects were observed for plasma SOD (p < 0.0001) and IL-6 (p < 0.0001) in the postexercise period. Overall results from our study do not support the notion that 4 weeks of daily soy milk ingestion can attenuate systemic elevations in markers of inflammation or oxidative defense. However, data do suggest that the downhill-running protocol utilized in this study can be effective in altering systemic markers of inflammation and oxidative defense enzyme activity, and that the ingestion of soy may help prevent fluctuations in plasma TNF-alpha.

Effects of age and sedentary lifestyle on skeletal muscle NF-kappaB signaling in men.

BACKGROUND: Nuclear factor kappa B (NF-kappaB) is a critical signaling molecule of disuse-induced skeletal muscle atrophy. However, few studies have carefully investigated whether similar pathways are modulated with physical activity and age. METHODS: The present study examined lean mass, maximal force production, and skeletal muscle NF-kappaB signaling in 41 men categorized as sedentary (OS, N = 13, 63.85 +/- 6.59 year), physically active (OA, N = 14, 60.71 +/- 5.54 year), or young and sedentary (YS, N = 14, 21.35 +/- 3.84 year). Muscle tissue from the vastus lateralis was assayed for messenger RNA (mRNA) expression of the beta subunit of IkB kinase (IKKbeta), cytosolic protein content of phosphorylated inhibitor of kappa B alpha (pIKBalpha), and nuclear content of NF-kappaB subunits p50 and p65. RESULTS: When compared with YS, OS demonstrated age-related muscle atrophy and reduced isokinetic knee extension torque. Physical activity in older individuals preserved maximal isokinetic knee extension torque. OS muscle contained 50% more pIKBalpha than OA and 61% more pIKBalpha than YS. Furthermore, nuclear p65 was significantly elevated in OS compared with YS. OS muscle did not differ from either of the other two groups for nuclear p50 or for mRNA expression of IKKbeta. CONCLUSIONS: These results indicate that skeletal muscle content of nuclear-bound p65 is elevated by age in humans. The elevation in nuclear-bound p65 appears to be at least partially due to significant increases in pIKBalpha. A sedentary lifestyle appears to play some role in increased IKBalpha; however, further research is needed to identify downstream effects of this increase.

Soymilk supplementation does not alter plasma markers of inflammation and oxidative stress in postmenopausal women.

Aging is associated with increasing levels of systemic inflammation and oxidative stress, both of which contribute to the progression of cardiovascular disease. Attenuation of such processes via dietary intervention has significant public health implications. Soyfoods, as a source of high-quality protein and isoflavones, may improve such indices, although such effects in healthy aging women are not well delineated. The purpose of this study was to test the hypothesis that 4 weeks of daily soymilk consumption would improve systemic markers of inflammation and oxidative stress in postmenopausal women when compared with a dairy control. In September 2009, a single-blind, randomized, controlled trial was conducted on 31 postmenopausal women at Baylor University, Waco, Tex. Subjects were randomly assigned to consume 3 servings of vanilla soy (n = 16) or reduced fat dairy (n = 15) milk per day for 4 weeks. Plasma markers of inflammation (tumor necrosis factor alpha [TNF-alpha], interleukin [IL]-1beta, IL-6) and oxidative stress (superoxide dismutase [SOD], glutathione peroxidase [GPx], cyclooxygenase-2 [COX-2]) were obtained before and after supplementation. No significant differences were observed for any of the plasma inflammatory (TNF-alpha, P = .08; IL-1beta, P = .14; IL-6, P = .26) or oxidative stress (SOD, P = .68; GPx, P = .58; COX-2, P = .99) variables by dietary treatment group. Despite good dietary compliance, our study failed to show a significant effect of soymilk consumption on markers of inflammation and oxidative stress in this postmenopausal female population. Potential reasons for this nonsignificant finding are discussed, and future research directions are presented.

Effects of eccentric treadmill exercise on inflammatory gene expression in human skeletal muscle.

The present study examined the skeletal muscle expression of several genes related to the inflammatory process before and after a bout of downhill running. Twenty-nine males between the ages of 18 and 35 years performed a 45-min downhill (-17.5%) treadmill protocol at 60% of maximal oxygen consumption. Venous bloods samples and muscle biopsy samples from the vastus lateralis were donated prior to and at 3-h and 24-h postexercise, along with ratings of perceived muscle soreness. Serum creatine kinase (CK) was determined, as was skeletal muscle gene expression of interleukin (IL)-6, IL-8, IL-12 (p35), tumor necrosis factor-alpha (TNF-alpha), IL-1beta, cyclooxygenase 2 (COX2), and nuclear factor kappa B (NFkB) (p105/p50). Gene expression was analyzed using RT-PCR and compared with a standard housekeeping gene (beta-actin). Data were analyzed for statistical differences using multivariate analysis of variance with univariate follow-up. In addition, Pearson correlations were conducted to determine if any significant relationship exists between any of these transcripts and both CK and muscle soreness. Significant (p < 0.05) up-regulations in IL-6, IL-8, and COX2 mRNA expression were observed compared with baseline, whereas no significant changes for IL-12, IL-1beta, TNF-alpha, or NFkB were noted. Significant increases in IL-6 mRNA were observed at 3 h (p < 0.001) and 24 h (p = 0.043), whereas significant increases in IL-8 (p = 0.001) and COX2 (p = 0.046) mRNA were observed at 3-h postexercise. In addition, muscle soreness was significantly correlated with IL-8 at 24 h (r = -0.370; p = 0.048), whereas CK was significantly related to NFkB at baseline (r = -0.460; p = 0.012). These data indicate that increases in the mRNA expression of IL-6, IL-8, and COX2 occur in the vastus lateralis as a result of damaging eccentric exercise in young, recreationally trained males. Further, it appears that IL-8 transcription may play some role in inhibiting postexercise muscle soreness, possibly through regulation of angiogenesis.

Resistance exercise-induced changes of inflammatory gene expression within human skeletal muscle.

Aberrant local inflammatory signaling within skeletal muscle is now considered a contributing factor to the development of sarcopenia. Recent evidence indicates that chronic resistance training contributes to the control of locally derived inflammation via adaptations to repeated, acute increases in pro-inflammatory mRNA within muscle. However, only a limited number of gene transcripts related to the inflammatory process have been examined in the literature. The present study utilized an acute bout to examine the effects of resistance exercise on several inflammatory-related genes in 24 physically active, post-menopausal women not currently undergoing hormone replacement therapy. Following a standard warm-up, participants completed a lower-body resistance exercise bout consisting of 3 sets of 10 repetitions on machine squat, leg press, and leg extension exercises (80% intensity). Muscle biopsies were obtained from the vastus lateralis of the dominant leg at baseline and 3 h following exercise. Significant (p < 0.05) up-regulation in mRNA content was observed for TNFalpha, IL1beta, IL6, IL8, SOCS2, COX2, SAA1, SAA2, IKKB, cfos, and junB. Muscle mRNA content was not significantly altered at the 0.05 level for IL2, IL5, IL10, or IL12 (p35). Venous blood samples were also obtained at baseline as well as at 3, 24, and 48 h post-exercise. Serum was analyzed for circulating TNFalpha, IL1beta, IL6, IL8, COX2, and SAA with no significant changes observed. These results indicate that resistance exercise is capable of up-regulating transcription of numerous inflammatory mediators within skeletal muscle, and these appear to be worthy of future examination in chronic studies.