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In a pilot randomized clinical trial, participants aged ≥60 years (n = 35) with physical limitations and symptomatic knee osteoarthritis (OA) were randomized to 12 weeks of lower-body low-load resistance training with blood-flow restriction (BFR) or moderate-intensity resistance training (MIRT) to evaluate changes in muscle strength, pain, and physical function. Four exercises were performed three times per week to volitional fatigue using 20% and 60% of one repetition maximum (1RM). Study outcomes included knee extensor strength, gait speed, Short Physical Performance Battery (SPPB) performance, and pain via the Western Ontario and McMaster Universities OA Index (WOMAC). Per established guidance for pilot studies, primary analyses for the trial focused on safety, feasibility, and effect sizes/95% confidence intervals of dependent outcomes to inform a fully-powered trial. Across three speeds of movement, the pre- to post-training change in maximal isokinetic peak torque was 9.96 (5.76, 14.16) Nm while the mean difference between groups (BFR relative to MIRT) was -1.87 (-10.96, 7.23) Nm. Most other directionally favored MIRT, though more spontaneous reports of knee pain were observed (n = 14) compared to BFR (n = 3). BFR may have lower efficacy than MIRT in this context-though a fully-powered trial is needed to definitively address this hypothesis.
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Skeletal muscle mitochondrial function declines with age and is a key factor in the maintenance of physical function among older adults. Research studies from animals and humans have consistently demonstrated that exercise improves skeletal muscle mitochondrial function in early and middle adulthood. However, mitochondrial adaptations to both acute and chronic exercise are attenuated in late life. Thus, there is an important need to identify adjuvant therapies capable of augmenting mitochondrial adaptations to exercise (e.g. improved mitochondrial respiration, muscle mitochondria biogenesis) among older adults. This study is investigating the potential of resveratrol supplementation for this purpose. The objective of this randomized, double-masked pilot trial is to evaluate the efficacy of resveratrol supplementation combined with a comprehensive supervised exercise program exercise for improving physical function among older adults. Moderately functioning, sedentary participants aged ≥60 years will perform 24 sessions (2 day/wk for 12 weeks) of center-based walking and resistance training and are randomly assigned to receive either (1) 500 mg/day resveratrol (2) 1000 mg/day resveratrol or (3) placebo. Study dependent outcomes include changes in 1) knee extensor strength, 2) objective measures of physical function (e.g. 4m walk test, Short Physical Performance Battery), 3) subjective measures of physical function assessed by Late Life Function and Disability Instrument, and 4) skeletal muscle mitochondrial function. This study will provide novel information regarding the therapeutic potential of resveratrol supplementation combined with exercise while also informing about the long-term clinical viability of the intervention by evaluating participant safety and willingness to engage in the intervention.
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Persons aged over 65 years account for over the vast majority of healthcare expenditures and deaths attributable to cardiovascular disease (CVD). Accordingly, reducing CVD risk among older adults is an important public health priority. Structured physical activity (i.e. exercise) is a well-documented method of decreasing CVD risk, but recent large-scale trials suggest that exercise alone is insufficient to reduce CVD events in high-risk populations of older adults. Thus adjuvant strategies appear necessary to reduce CVD risk. Accumulating evidence indicates that prolonged sedentary behavior (e.g. sitting) has detrimental health effects that are independent of engagement in recommended levels of moderate-intensity exercise. Yet clinical trials in this area are lacking. We hypothesize that exercise, when combined with a novel technology based intervention specifically designed to reduce sedentary behavior will reduce CVD risk among sedentary older adults. The purpose of this study is to evaluate the feasibility and efficacy of combining a traditional, structured exercise intervention with an innovative intervention designed to decrease sedentary behavior and increase non-exercise physical activity (NEPA). This study will provide us with critical data necessary to design and implement a full-scale trial to test our central hypothesis. Participants aged ≥60 years with moderate to high risk of coronary heart disease (CHD) events are randomly assigned to either the exercise and technology intervention (EX+NEPA) or exercise alone (EX) groups. Study dependent outcomes include changes in 1) daily activity patterns, 2) blood pressure, 3) exercise capacity, 4) waist circumference, and 5) circulating indices of cardiovascular function. This study will provide critical information for designing a fully-powered clinical trial, which could have health implications for the ever increasing population of older adults.
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OBJECTIVES: To examine associations between objectively measured physical activity (PA) and incidence of major mobility disability (MMD) and persistent MMD (PMMD) in older adults in the Lifestyle Interventions and Independence for Elders (LIFE) Study. DESIGN: Prospective cohort of individuals aged 65 and older undergoing structured PA intervention or health education. SETTING: The LIFE Study was a multicenter (eight sites) randomized controlled trial designed to compare the efficacy of a long-term structured PA intervention with that of a health education (HE) program in reducing the incidence of MMD in mobility-limited older adults. PARTICIPANTS: LIFE Study participants (n = 1,590) had a mean age±standard deviation of 78.9 ± 5.2, low levels of PA, and measured mobility-relevant functional impairment at baseline. MEASUREMENTS: Activity data were collected using hip-worn 7-day accelerometers at baseline and 6, 12, and 24 months after randomization to test for associations with incident MMD and PMMD (≥2 consecutive instances of MMD). RESULTS: At baseline, every 30 minutes spent being sedentary (<100 accelerometry counts per minute) was associated with higher rate of subsequent MMD (10%) and PMMD (11%) events. Every 500 steps taken was associated with lower rate of MMD (15%) and PMMD (18%). Similar associations were observed when fitting accelerometry-based PA as a time-dependent variable. CONCLUSION: Accelerometry-based PA levels were strongly associated with MMD and PMMD events in older adults with limited mobility. These results support the importance of daily PA and lower amounts of sedentary time levels in this population and suggest that accelerometry may be a useful tool for assessing risk of mobility disability.
Assuntos
Acelerometria/métodos , Avaliação da Deficiência , Exercício Físico , Avaliação Geriátrica/métodos , Limitação da Mobilidade , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Modalidades de Fisioterapia , Comportamento Sedentário , Fatores de TempoRESUMO
OBJECTIVES: To evaluate the extent of variability in functional responses in participants in the Lifestyle Interventions and Independence for Elders (LIFE) study and to identify the relative contributions of intervention adherence, physical activity, and demographic and health characteristics to this variability. DESIGN: Secondary analysis. SETTING: Multicenter institutions. PARTICIPANTS: A volunteer sample (N=1635) of sedentary men and women aged 70 to 89 years who were able to walk 400m but had physical limitations, defined as a Short Physical Performance Battery (SPPB) score of ≤9. INTERVENTIONS: Moderate-intensity physical activity (n=818) consisting of aerobic, resistance, and flexibility exercises performed both center-based (2times/wk) and home-based (3-4times/wk) sessions or health education program (n=817) consisting of weekly to monthly workshops covering relevant health information. MAIN OUTCOME MEASURES: Physical function (gait speed over 400m) and lower extremity function (SPPB score) assessed at baseline and 6, 12, and 24 months. RESULTS: Greater baseline physical function (gait speed, SPPB score) was negatively associated with change in gait speed (regression coefficient ß=-.185; P<.001) and change in SPPB score (ß=-.365; P<.001), whereas higher number of steps per day measured by accelerometry was positively associated with change in gait speed (ß=.035; P<.001) and change in SPPB score (ß=.525; P<.001). Other baseline factors associated with positive change in gait speed and/or SPPB score include younger age (P<.001), lower body mass index (P<.001), and higher self-reported physical activity (P=.002). CONCLUSIONS: Several demographic and physical activity-related factors were associated with the extent of change in functional outcomes in participants in the LIFE study. These factors should be considered when designing interventions for improving physical function in older adults with limited mobility.
Assuntos
Exercício Físico/fisiologia , Educação em Saúde , Extremidade Inferior/fisiologia , Limitação da Mobilidade , Acelerometria , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Pressão Sanguínea , Índice de Massa Corporal , Feminino , Humanos , Masculino , Cooperação do Paciente , Condicionamento Físico Humano/métodos , Treinamento Resistido , Comportamento Sedentário , Fatores de Tempo , Velocidade de Caminhada/fisiologiaRESUMO
We investigated the acute myogenic response to resistance exercise with and without blood-flow restriction (BFR). Six men and women (age, 22 ± 1 years) performed unilateral knee extensions at 40% of 1-repetition maximum with or without (CNTRL) BFR applied via pressure cuff inflated to 220 mm Hg. Muscle biopsies were collected at 4 h and 24 h postexercise. Addition of BFR increased myoD and c-Met messenger RNA expression relative to CNTRL. Expression of hepatocyte growth factor protein was significantly higher following CNTRL.
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Fator de Crescimento de Hepatócito/metabolismo , Desenvolvimento Muscular , Proteína MyoD/metabolismo , Proteínas Proto-Oncogênicas c-met/metabolismo , Músculo Quadríceps/metabolismo , Treinamento Resistido/métodos , Regulação para Cima , Adolescente , Adulto , Biomarcadores/metabolismo , Biópsia por Agulha , Constrição , Estudos Cross-Over , Feminino , Regulação da Expressão Gênica , Fator de Crescimento de Hepatócito/genética , Humanos , Masculino , Proteína MyoD/genética , Proteínas Proto-Oncogênicas c-met/genética , Músculo Quadríceps/crescimento & desenvolvimento , RNA Mensageiro/metabolismo , Fatores de Tempo , Adulto JovemRESUMO
South, MA, Layne, AS, Stuart, CA, Triplett, NT, Ramsey, MW, Howell, ME, Sands, WA, Mizuguchi, S, Hornsby, WG, Kavanaugh, AA, and Stone, MH. Effects of short-term free-weight and semiblock periodization resistance training on metabolic syndrome. J Strength Cond Res 30(10): 2682-2696, 2016-The effects of short-term resistance training on performance and health variables associated with prolonged sedentary lifestyle and metabolic syndrome (MS) were investigated. Resistance training may alter a number of health-related, physiological, and performance variables. As a result, resistance training can be used as a valuable tool in ameliorating the effects of a sedentary lifestyle including those associated with MS. Nineteen previously sedentary subjects (10 with MS and 9 with nonmetabolic syndrome [NMS]) underwent 8 weeks of supervised resistance training. Maximum strength was measured using an isometric midthigh pull and resulting force-time curve. Vertical jump height (JH) and power were measured using a force plate. The muscle cross-sectional area (CSA) and type were examined using muscle biopsy and standard analysis techniques. Aerobic power was measured on a cycle ergometer using a ParvoMedics 2400 Metabolic system. Endurance was measured as time to exhaustion on a cycle ergometer. After training, maximum isometric strength, JH, jump power, and V[Combining Dot Above]O2peak increased by approximately 10% (or more) in both the metabolic and NMS groups (both male and female subjects). Over 8 weeks of training, body mass did not change statistically, but percent body fat decreased in subjects with the MS and in women, and lean body mass increased in all groups (p ≤ 0.05). Few alterations were noted in the fiber type. Men had larger CSAs compared those of with women, and there was a fiber-specific trend toward hypertrophy over time. In summary, 8 weeks of semiblock free-weight resistance training improved several performance variables and some cardiovascular factors associated with MS.
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Síndrome Metabólica/terapia , Treinamento Resistido/métodos , Adulto , Composição Corporal/fisiologia , Distribuição da Gordura Corporal , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fibras Musculares Esqueléticas/patologia , Força Muscular/fisiologia , Consumo de Oxigênio/fisiologia , Fatores Sexuais , Adulto JovemRESUMO
AMP-activated protein kinase (AMPK) is a master regulator of metabolism. While muscle-specific AMPK ß1ß2 double-knockout (ß1ß2M-KO) mice display alterations in metabolic and mitochondrial capacity, their severe exercise intolerance suggested a secondary contributor to the observed phenotype. We find that tibialis anterior (TA), but not soleus, muscles of sedentary ß1ß2M-KO mice display a significant myopathy (decreased myofiber areas, increased split and necrotic myofibers, and increased centrally nucleated myofibers. A mitochondrial- and fiber-type-specific etiology to the myopathy was ruled out. However, ß1ß2M-KO TA muscles displayed significant (P<0.05) increases in platelet aggregation and apoptosis within myofibers and surrounding interstitium (P<0.05). These changes correlated with a 45% decrease in capillary density (P<0.05). We hypothesized that the ß1ß2M-KO myopathy in resting muscle resulted from impaired AMPK-nNOSµ signaling, causing increased platelet aggregation, impaired vasodilation, and, ultimately, ischemic injury. Consistent with this hypothesis, AMPK-specific phosphorylation (Ser1446) of nNOSµ was decreased in ß1ß2M-KO compared to wild-type (WT) mice. The AMPK-nNOSµ relationship was further demonstrated by administration of 5-aminoimidazole-4-carboxamide 1-ß-D-ribofuranoside (AICAR) to ß1ß2-MKO muscles and C2C12 myotubes. AICAR significantly increased nNOSµ phosphorylation and nitric oxide production (P<0.05) within minutes of administration in WT muscles and C2C12 myotubes but not in ß1ß2M-KO muscles. These findings highlight the importance of the AMPK-nNOSµ pathway in resting skeletal muscle.
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Proteínas Quinases Ativadas por AMP/genética , Capilares/metabolismo , Músculo Esquelético/patologia , Doenças Musculares/patologia , Óxido Nítrico/metabolismo , Proteínas Quinases Ativadas por AMP/metabolismo , Aminoimidazol Carboxamida/análogos & derivados , Aminoimidazol Carboxamida/metabolismo , Animais , Linhagem Celular , Complexo IV da Cadeia de Transporte de Elétrons/metabolismo , Feminino , Isquemia/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Mitocôndrias/metabolismo , Músculo Esquelético/irrigação sanguínea , Necrose/metabolismo , Fosforilação , Agregação Plaquetária , Ribonucleotídeos/metabolismo , Succinato Desidrogenase/metabolismoRESUMO
CONTEXT: The metabolic syndrome, characterized by central obesity with dyslipidemia, hypertension, and hyperglycemia, identifies people at high risk for type 2 diabetes. OBJECTIVE: Our objective was to determine how the insulin resistance of the metabolic syndrome is related to muscle fiber composition. DESIGN: Thirty-nine sedentary men and women (including 22 with the metabolic syndrome) had insulin responsiveness quantified using euglycemic clamps and underwent biopsies of the vastus lateralis muscle. Expression of insulin receptors, insulin receptor substrate-1, glucose transporter 4, and ATP synthase were quantified with immunoblots and immunohistochemistry. PARTICIPANTS AND SETTING: Participants were nondiabetic, metabolic syndrome volunteers and sedentary control subjects studied at an outpatient clinic. MAIN OUTCOME MEASURES: Insulin responsiveness during an insulin clamp and the fiber composition of a muscle biopsy specimen were evaluated. RESULTS: There were fewer type I fibers and more mixed (type IIa) fibers in metabolic syndrome subjects. Insulin responsiveness and maximal oxygen uptake correlated with the proportion of type I fibers. Insulin receptor, insulin receptor substrate-1, and glucose transporter 4 expression were not different in whole muscle but all were significantly less in the type I fibers of metabolic syndrome subjects when adjusted for fiber proportion and fiber size. Fat oxidation and muscle mitochondrial expression were not different in the metabolic syndrome subjects. CONCLUSION: Lower proportion of type I fibers in metabolic syndrome muscle correlated with the severity of insulin resistance. Even though whole muscle content was normal, key elements of insulin action were consistently less in type I muscle fibers, suggesting their distribution was important in mediating insulin effects.
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Resistência à Insulina , Síndrome Metabólica/patologia , Fibras Musculares de Contração Lenta/patologia , Músculo Quadríceps/patologia , Complexos de ATP Sintetase/metabolismo , Adulto , Antígenos CD/metabolismo , Índice de Massa Corporal , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/etiologia , Feminino , Transportador de Glucose Tipo 4/metabolismo , Humanos , Proteínas Substratos do Receptor de Insulina/metabolismo , Masculino , Síndrome Metabólica/complicações , Síndrome Metabólica/metabolismo , Pessoa de Meia-Idade , Fibras Musculares de Contração Rápida/enzimologia , Fibras Musculares de Contração Rápida/metabolismo , Fibras Musculares de Contração Rápida/patologia , Fibras Musculares de Contração Lenta/enzimologia , Fibras Musculares de Contração Lenta/metabolismo , Obesidade/complicações , Músculo Quadríceps/enzimologia , Músculo Quadríceps/metabolismo , Receptor de Insulina/metabolismo , Risco , Comportamento Sedentário , Tennessee/epidemiologiaRESUMO
CONTEXT: Strength training induces muscle remodeling and may improve insulin responsiveness. OBJECTIVE: This study will quantify the impact of resistance training on insulin sensitivity in subjects with the metabolic syndrome and correlate this with activation of intramuscular pathways mediating mitochondrial biogenesis and muscle fiber hypertrophy. DESIGN: Ten subjects with the metabolic syndrome (MS) and nine sedentary controls underwent 8 wk of supervised resistance exercise training with pre- and posttraining anthropometric and muscle biochemical assessments. SETTING: Resistance exercise training took place in a sports laboratory on a college campus. MAIN OUTCOME MEASURES: Pre- and posttraining insulin responsiveness was quantified using a euglycemic clamp. Changes in expression of muscle 5-AMP-activated protein kinase (AMPK) and mammalian target of rapamycin (mTOR) pathways were quantified using immunoblots. RESULTS: Strength and stamina increased in both groups. Insulin sensitivity increased in controls (steady-state glucose infusion rate = 7.0 ± 2.0 mg/kg · min pretraining training vs. 8.7 ± 3.1 mg/kg · min posttraining; P < 0.01) but did not improve in MS subjects (3.3 ± 1.3 pre vs. 3.1 ± 1.0 post). Muscle glucose transporter 4 increased 67% in controls and 36% in the MS subjects. Control subjects increased muscle phospho-AMPK (43%), peroxisome proliferator-activated receptor γ coactivator 1α (57%), and ATP synthase (60%), more than MS subjects (8, 28, and 21%, respectively). In contrast, muscle phospho-mTOR increased most in the MS group (57 vs. 32%). CONCLUSION: Failure of resistance training to improve insulin responsiveness in MS subjects was coincident with diminished phosphorylation of muscle AMPK, but increased phosphorylation of mTOR, suggesting activation of the mTOR pathway could be involved in inhibition of exercise training-related increases in AMPK and its activation and downstream events.