Insight into the Molecular Signature of Skeletal Muscle Characterizing Lifelong Football Players.

BACKGROUND: Aging and sedentary behavior are independent risk factors for non-communicable diseases. An active lifestyle and structured physical activity are positively associated with a healthier quality of life in the elderly. Here, we explored the proteomic/metabolomic muscular signature induced by lifelong football training associated with successful aging. METHODS: The study was performed on nine lifelong football players (67.3 ± 2.8 yrs) and nine aged-matched untrained subjects. We performed a proteomic/metabolomic approach on V. lateralis muscle biopsies; the obtained data were analyzed by means of different bioinformatic tools. RESULTS: Our results indicated that lifelong football training is able to enhance the muscles' oxidative capacity in the elderly by promoting fatty acids as preferential energetic substrates and hence determining a healthier body composition and metabolic profile; furthermore, we showed that the total polyamine content is higher in lifelong football players' muscle, enforcing the involvement of polyamines in muscle growth and hypertrophy. CONCLUSIONS: Lifelong football training, as a structured physical activity, significantly influences the expression of the proteins and metabolites involved in oxidative metabolism and muscle hypertrophy associated with successful aging.

Acute arm and leg muscle glycogen and metabolite responses to small-sided football games in healthy young men.

PURPOSE: Studies have indicated upper body involvement during football, provoking long-term muscular adaptations. This study aimed at examining the acute metabolic response in upper and lower body skeletal muscle to football training organized as small-sided games (SSG). METHODS: Ten healthy male recreational football players [age 24 ± 1 (± SD) yrs; height 183 ± 4 cm; body mass 83.1 ± 9.7 kg; body fat 15.5 ± 5.4%] completed 1-h 5v5 SSG (4 × 12 min interspersed with 4-min recovery periods). Muscle biopsies were obtained from m. vastus lateralis (VL) and m. deltoideus (DE) pre- and post-SSG for muscle glycogen and metabolite analyses. Blood lactate samples were obtained at rest, middle and end of the SSG. RESULTS: Muscle glycogen in VL decreased (P < 0.01) by 21% and tended (P = 0.08) to decrease in DE by 13%. Muscle lactate increased in VL (117%; P < 0.001) and DE (81%; P < 0.001) during the game, while blood lactate rose threefold. Muscle ATP and PCr were unaltered, but intermuscular differences were detected for ATP at both time points (P < 0.001) and for PCr at pre-SSG (P < 0.05) with VL demonstrating higher values than DE, while muscle creatine rose in VL (P < 0.001) by 41% and by 22% in DE (P = 0.02). Baseline citrate synthase maximal activity was higher (P < 0.05) in VL compared to DE, whereas baseline muscle lactate concentration was higher (P < 0.05) in DE than VL. CONCLUSION: The upper body may be extensively involved during football play, but besides a rise in muscle lactate in the deltoideus muscle similar to the leg muscles, the present study did not demonstrate acute metabolic changes of an order that may explain the previously reported training effect of football play in the upper extremities.

Lifelong Football Training: Effects on Autophagy and Healthy Longevity Promotion.

Aging is a physiological process characterized by a progressive decline of biological functions and an increase in destructive processes in cells and organs. Physical activity and exercise positively affects the expression of skeletal muscle markers involved in longevity pathways. Recently, a new mechanism, autophagy, was introduced to the adaptations induced by acute and chronic exercise as responsible of positive metabolic modification and health-longevity promotion. However, the molecular mechanisms regulating autophagy in response to physical activity and exercise are sparsely described. We investigated the long-term adaptations resulting from lifelong recreational football training on the expression of skeletal muscle markers involved in autophagy signaling. We demonstrated that lifelong football training increased the expression of messengers: RAD23A, HSPB6, RAB1B, TRAP1, SIRT2, and HSBPB1, involved in the auto-lysosomal and proteasome-mediated protein degradation machinery; of RPL1, RPL4, RPL36, MRLP37, involved in cellular growth and differentiation processes; of the Bcl-2, HSP70, HSP90, PSMD13, and of the ATG5-ATG12 protein complex, involved in proteasome promotion and autophagy processes in muscle samples from lifelong trained subjects compared to age-matched untrained controls. In conclusion, our results indicated that lifelong football training positively influence exercise-induced autophagy processes and protein quality control in skeletal muscle, thus promoting healthy aging.

Positive effects of 1-year football and strength training on mechanical muscle function and functional capacity in elderly men.

PURPOSE: A decline in physical capacity takes place with increasing age that negatively affects overall physical function including work ability and the ability to perform typical activities of daily living (ADL). The overall aim of the present study was to determine the neuromuscular adaptations to long-term (1 year) football and strength training in older untrained adults, and to assess the concurrent effect on functional ADL capacity. METHODS: Twenty-seven healthy elderly males (68.2 ± 3.2 years) were randomly assigned to 12 months of either recreational football training (FT: n = 10), strength training (ST: n = 9) or served as inactive controls (CON: n = 8). Recreational football training consisted of small-sided training sessions whereas strength training consisted of high intensity exercises targeting the lower extremity and upper body. Maximal thigh muscle strength and rate of force development (RFD) were assessed with isokinetic dynamometry, while postural balance and vertical jumping performance were evaluated using force plate analysis. Furthermore, functional ability was evaluated by stair-ascent and chair-rising testing. RESULTS: A total of nine, nine and seven participants from FT, ST and CON, respectively, were included in the analysis. Both exercise regimens led to substantial gains in functional ability, evidenced by 24 and 18 % reduced stair-ascent time, and 32 and 21 % increased chair-rising performance in FT and ST, respectively (all P < 0.05). Long-term strength training led to increased concentric (14 %; P < 0.01) and isometric (23 %; P < 0.001) quadriceps and isometric hamstring strength (44 %; P < 0.0001), whereas football training mainly resulted in enhanced hamstring strength (18 %, P < 0.05) and RFD (89 %, P < 0.0001). CONCLUSIONS: Long-term (1 year) strength training led to increased quadriceps and hamstring strength, whereas the adaptations to football training mainly included enhanced strength and rapid force capacity of the hamstring muscles. Gains in functional ability were observed in response to both training regimens, evidenced by reduced stair-ascent time and increased chair-rising performance. Long-term football exercise and strength training both appear to be effective interventional strategies to improve factors of importance for ADL by counteracting the age-related decline in lower limb strength and functional capacity among old male adults. This could potentially be a way to improve work ability of senior workers.

The mechanistic bases of the power-time relationship: muscle metabolic responses and relationships to muscle fibre type.

KEY POINTS: The power-asymptote (critical power; CP) of the hyperbolic power-time relationship for high-intensity exercise defines a threshold between steady-state and non-steady-state exercise intensities and the curvature constant (W') indicates a fixed capacity for work >CP that is related to a loss of muscular efficiency. The present study reports novel evidence on the muscle metabolic underpinnings of CP and W' during whole-body exercise and their relationships to muscle fibre type. We show that the W' is not correlated with muscle fibre type distribution and that it represents an elevated energy contribution from both oxidative and glycolytic/glycogenolytic metabolism. We show that there is a positive correlation between CP and highly oxidative type I muscle fibres and that muscle metabolic steady-state is attainable CP. Our findings indicate a mechanistic link between the bioenergetic characteristics of muscle fibre types and the power-time relationship for high-intensity exercise. ABSTRACT: We hypothesized that: (1) the critical power (CP) will represent a boundary separating steady-state from non-steady-state muscle metabolic responses during whole-body exercise and (2) that the CP and the curvature constant (W') of the power-time relationship for high-intensity exercise will be correlated with type I and type IIx muscle fibre distributions, respectively. Four men and four women performed a 3 min all-out cycling test for the estimation of CP and constant work rate (CWR) tests slightly >CP until exhaustion (Tlim ), slightly CP Tlim isotime to test the first hypothesis. Eleven men performed 3 min all-out tests and donated muscle biopsies to test the second hypothesis. Below CP, muscle [PCr] [42.6 ± 7.1 vs. 49.4 ± 6.9 mmol (kg d.w.)(-1) ], [La(-) ] [34.8 ± 12.6 vs. 35.5 ± 13.2 mmol (kg d.w.)(-1) ] and pH (7.11 ± 0.08 vs. 7.10 ± 0.11) remained stable between ∼12 and 24 min (P > 0.05 for all), whereas these variables changed with time >CP such that they were greater [[La(-) ] 95.6 ± 14.1 mmol (kg d.w.)(-1) ] and lower [[PCr] 24.2 ± 3.9 mmol (kg d.w.)(-1) ; pH 6.84 ± 0.06] (P < 0.05) at Tlim (740 ± 186 s) than during the

The Effects of 52 Weeks of Soccer or Resistance Training on Body Composition and Muscle Function in +65-Year-Old Healthy Males--A Randomized Controlled Trial.

The effects of 52 weeks of soccer or resistance training were investigated in untrained elderly men. The subjects aged 68.1±2.1 yrs were randomised into a soccer (SG; n = 9), a resistance (RG; n = 9) and a control group (CG; n = 8). The subjects in SG and RG, respectively, trained 1.7±0.3 and 1.8±0.3 times weekly on average during the intervention period. Muscle function and body composition were determined before and after 16 and 52 weeks of the intervention period. In SG, BMI was reduced by 1.5% and 3.0% (p<0.05) after 16 and 52 weeks, respectively, unchanged in RG and 2% higher (p<0.05) in CG after 52 weeks of the intervention period. In SG, the response to a glucose tolerance test was 16% lower (p<0.05) after 16 wks, but not after 52 wks, compared to before the intervention period, and unchanged in RG and CG. In SG, superoxide dismutase-2 expression was 59% higher (p<0.05) after 52 wks compared to before the intervention period, and unchanged in RG and CG. In RG, upper body lean mass was 3 and 2% higher (p<0.05) after 16 and 52 wks, respectively, compared to before the intervention period, and unchanged in SG and CG. In RG, Akt-2 expression increased by 28% (p<0.01) and follistatin expression decreased by 38% (p<0.05) during the 52-wk intervention period, and was unchanged in SG and CG. Thus, long-term soccer training reduces BMI and improves anti-oxidative capacity, while long-term resistance training impacts muscle protein enzyme expression and increases lean body mass in elderly men. Trial Registration: ClinicalTrials.gov: NCT01530035.

Effects of Exercise Training on Regulation of Skeletal Muscle Glucose Metabolism in Elderly Men.

BACKGROUND: The aim was to investigate the molecular mechanisms behind exercise training-induced improvements in glucose regulation in aged subjects. METHODS: Twelve elderly male subjects completed 8 weeks of exercise training. Before and after the training period, the subjects completed an oral glucose tolerance test (OGTT) and a muscle biopsy was obtained from the vastus lateralis before and 45 minutes into the OGTT. Blood samples were collected before and up to 120 minutes after glucose intake. RESULTS: Exercise training increased Hexokinase II, GLUT4, Akt2, glycogen synthase (GS), pyruvate dehydrogenase (PDH)-E1α, PDK2 protein, and glycogen content in skeletal muscle. Furthermore, in response to glucose, GS activity was increased and the dephosphorylation of GS site 2 + 2a and 3a was enhanced after the training intervention. The glucose-mediated insulin stimulation of TBC1D4 Thr(642) phosphorylation was increased after exercise training. In the trained state, the PDHa activity was reduced following glucose intake and without changes in phosphorylation level of PDH-E1α. CONCLUSIONS: The present results suggest that exercise training improves glucose regulation in elderly subjects by enhancing the capacity and acute regulation of glucose uptake and by enhancing intracellular glucose removal to glycogen synthesis rather than glucose oxidation.

Resveratrol modulates the angiogenic response to exercise training in skeletal muscles of aged men.

In animal studies, the polyphenol resveratrol has been shown to influence several pathways of importance for angiogenesis in skeletal muscle. The aim of the present study was to examine the angiogenic effect of resveratrol supplementation with parallel exercise training in aged men. Forty-three healthy physically inactive aged men (65 ± 1 yr) were divided into 1) a training group that conducted 8 wk of intense exercise training where half of the subjects received a daily intake of either 250 mg trans-resveratrol (n = 14) and the other half received placebo (n = 13) and 2) a nontraining group that received either 250 mg trans-resveratrol (n = 9) or placebo (n = 7). The group that trained with placebo showed a ~20% increase in the capillary-to-fiber ratio, an increase in muscle protein expression of VEGF, VEGF receptor-2, and tissue inhibitor of matrix metalloproteinase (TIMP-1) but unaltered thrombospodin-1 levels. Muscle interstitial VEGF and thrombospodin-1 protein levels were unchanged after the training period. The group that trained with resveratrol supplementation did not show an increase in the capillary-to-fiber ratio or an increase in muscle VEGF protein. Muscle TIMP-1 protein levels were lower in the training and resveratrol group than in the training and placebo group. Both training groups showed an increase in forkhead box O1 protein. In nontraining groups, TIMP-1 protein was lower in the resveratrol-treated group than the placebo-treated group after 8 wk. In conclusion, these data show that exercise training has a strong angiogenic effect, whereas resveratrol supplementation may limit basal and training-induced angiogenesis.

Effects of recreational soccer in men with prostate cancer undergoing androgen deprivation therapy: study protocol for the 'FC Prostate' randomized controlled trial.

BACKGROUND: Androgen deprivation therapy (ADT) is a cornerstone in the treatment of advanced prostate cancer. Adverse musculoskeletal and cardiovascular effects of ADT are widely reported and investigations into the potential of exercise to ameliorate the effects of treatment are warranted. The 'Football Club (FC) Prostate' study is a randomized trial comparing the effects of soccer training with standard treatment approaches on body composition, cardiovascular function, physical function parameters, glucose tolerance, bone health, and patient-reported outcomes in men undergoing ADT for prostate cancer. METHODS/DESIGN: Using a single-center randomized controlled design, 80 men with histologically confirmed locally advanced or disseminated prostate cancer undergoing ADT for 6 months or more at The Copenhagen University Hospital will be enrolled on this trial. After baseline assessments eligible participants will be randomly assigned to a soccer training group or a control group receiving usual care. The soccer intervention will consist of 12 weeks of training 2-3 times/week for 45-60 min after which the assessment protocol will be repeated. Soccer training will then continue bi-weekly for an additional 20 weeks at the end of which all measures will be repeated to allow for additional analyses of long-term effects. The primary endpoint is changes in lean body mass from baseline to 12 weeks assessed by dual X-ray absorptiometry scan. Secondary endpoints include changes of cardiovascular, metabolic, and physical function parameters, as well as markers of bone metabolism and patient-reported outcomes. DISCUSSION: The FC Prostate trial will assess the safety and efficacy of a novel soccer-training approach to cancer rehabilitation on a number of clinically important health outcomes in men with advanced prostate cancer during ADT. The results may pave the way for innovative, community-based interventions in the approach to treating prostate cancer. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01711892.

Cardiovascular effects of 3 months of football training in overweight children examined by comprehensive echocardiography: a pilot study.

We examined effects of a 3-month football training programme in overweight children using comprehensive echocardiography and peripheral arterial tonometry. Twenty preadolescent overweight children (17 boys, 3 girls aged 8-12 yrs; body mass index [BMI] ≥ 85(th) percentile) participated in a structured 3-month football training programme, consisting of 4 weekly 60-90 min sessions with mean heart rate (HR) > 80% of HRmax (football group, FG). A parallel control group (CG) included 11 children (7 boys, 4 girls) of equivalent age from an obesity clinic. After 3 months, systolic blood pressure was unchanged in FG, but had increased in CG (112 [s 6] vs. 122 [10] mmHg, P = 0.02). FG demonstrated increased left ventricular (LV) posterior wall diameter (0.60 [0.07] vs. 0.68 [0.10] cm, P < 0.001) and an improved right ventricular systolic function determined by tricuspid annular plane systolic excursion (TAPSE, 2.01 [0.29] vs. 2.27 [0.28] cm, P = 0.003). Measures of LV systolic function showed only discrete alterations and two-dimensional (2D) global strain was not changed. After 3 months, global isovolumetric relaxation time (IVRTglobal) had increased in FG (64.0 [7.5] vs. 73.9 [9.4] ms, P < 0.001) while other examined LV diastolic function variables were not altered. No echocardiographic changes were observed in CG. Between-group differences in pre-post delta values were observed for systolic blood pressure, TAPSE, and IVRTglobal (P = 0.02-0.03). We conclude that short-term football training may have positive structural and functional effects on the cardiovascular system in overweight preadolescent children.

Resveratrol blunts the positive effects of exercise training on cardiovascular health in aged men.

Ageing is thought to be associated with decreased vascular function partly due to oxidative stress. Resveratrol is a polyphenol, which in animal studies has been shown to decrease atherosclerosis, and improve cardiovascular health and physical capacity, in part through its effects on Sirtuin 1 signalling and through an improved antioxidant capacity. We tested the hypothesis that resveratrol supplementation enhances training-induced improvements in cardiovascular health parameters in aged men. Twenty-seven healthy physically inactive aged men (age: 65 ± 1 years; body mass index: 25.4 ± 0.7 kg m(-2); mean arterial pressure (MAP): 95.8 ± 2.2 mmHg; maximal oxygen uptake: 2488 ± 72 ml O2 min(-1)) were randomized into 8 weeks of either daily intake of either 250 mg trans-resveratrol (n = 14) or of placebo (n = 13) concomitant with high-intensity exercise training. Exercise training led to a 45% greater (P < 0.05) increase in maximal oxygen uptake in the placebo group than in the resveratrol group and to a decrease in MAP in the placebo group only (-4.8 ± 1.7 mmHg; P < 0.05). The interstitial level of vasodilator prostacyclin was lower in the resveratrol than in the placebo group after training (980 ± 90 vs. 1174 ± 121 pg ml(-1); P < 0.02) and muscle thromboxane synthase was higher in the resveratrol group after training (P < 0.05). Resveratrol administration also abolished the positive effects of exercise on low-density lipoprotein, total cholesterol/high-density lipoprotein ratio and triglyceride concentrations in blood (P < 0.05). Resveratrol did not alter the effect of exercise training on the atherosclerosis marker vascular cell adhesion molecule 1 (VCAM-1). Sirtuin 1 protein levels were not affected by resveratrol supplementation. These findings indicate that, whereas exercise training effectively improves several cardiovascular health parameters in aged men, concomitant resveratrol supplementation can blunt these effects.

Soccer training improves cardiac function in men with type 2 diabetes.

INTRODUCTION: Patients with type 2 diabetes mellitus (T2DM) have an increased risk of cardiovascular disease, which is worsened by physical inactivity. Subclinical myocardial dysfunction is associated with increased risk of heart failure and impaired prognosis in T2DM; however, it is not clear if exercise training can counteract the early signs of diabetic heart disease. PURPOSE: This study aimed to evaluate the effects of soccer training on cardiac function, exercise capacity, and blood pressure in middle-age men with T2DM. METHODS: Twenty-one men age 49.8 ± 1.7 yr with T2DM and no history of cardiovascular disease participated in a soccer training group (n = 12) that trained 1 h twice a week or a control group (n = 9) with no change in lifestyle. Examinations included comprehensive transthoracic echocardiography, measurements of blood pressure, maximal oxygen consumption (V(˙)O(2max)), and intermittent endurance capacity before and after 12 and 24 wk. Two-way repeated-measures ANOVA was applied. RESULTS: After 24 wk of soccer training, left ventricular (LV) end-diastolic diameter and volume were increased (P < 0.001) compared to baseline. LV longitudinal systolic displacement was augmented by 23% (P < 0.001) and global longitudinal two-dimensional strain increased by 10% (P < 0.05). LV diastolic function, determined by mitral inflow (E/A ratio) and peak diastolic velocity E', was increased by 18% (P < 0.01) and 29% (P < 0.001), respectively, whereas LV filling pressure E/E' was reduced by 15% (P = 0.05). Systolic, diastolic, and mean arterial pressures were all reduced by 8 mm Hg (P < 0.01, P < 0.001, and P < 0.001, respectively). V(˙)O(2max) and intermittent endurance capacity was 12% and 42% (P < 0.001) higher, respectively. No changes in any of the measured parameters were observed in control group. CONCLUSION: Regular soccer training improves cardiac function, increases exercise capacity, and lowers blood pressure in men with T2DM.