Biomedical subjects

Roger A Fielding

Publications and source records attributed to Roger A Fielding.

At least 19 recordsLinked to original sources

PubMed2007

Effects of metformin and rosiglitazone in HIV-infected patients with hyperinsulinemia and elevated waist/hip ratio.

OBJECTIVE: To evaluate the effects of metformin and rosiglitazone, alone or in combination, on fat distribution, insulin sensitivity, and lipids in HIV-infected patients with insulin resistance and changes in fat distribution. METHODS: A total of 105 subjects were randomly assigned to receive metformin (500 mg twice a day increasing to 1000 mg twice a day after 2 weeks) with rosiglitazone placebo (Met/P, N = 26); rosiglitazone (4 mg/day) with metformin placebo (Rosi/P, N = 27); rosiglitazone (4 mg/day) plus metformin (500 mg twice a day increasing to 1000 mg twice a day after 2 weeks; Met/Rosi, N = 25); or dual placebo (P/P, N = 27) for 16 weeks. Efficacy assessments included oral glucose tolerance testing, abdominal computed tomography, whole-body dual-energy X-ray absorptiometry, and the measurement of fasting lipids and other biochemical indices. Safety was monitored throughout. Intent-to-treat analyses were performed using non-parametric methods. RESULTS: The median insulin area under the curve (AUC) decreased significantly compared with baseline in both groups randomly assigned to rosiglitazone (Rosi/P -25.7 microIU/ml, P = 0.012; Met/Rosi -17.7 microIU/ml, P = 0.002); and tended to decrease in the Met/P group (-11.1 microIU/ml, P = 0.058). The change in AUC with combination therapy was significant compared with placebo (P = 0.032). No treatment was associated with significant changes in visceral or subcutaneous abdominal fat. Leg fat increased in subjects on Rosi/P compared with placebo (+4.8 versus -8.3%, P = 0.034). Rosiglitazone, but not metformin, increased adiponectin but also increased LDL-cholesterol and decreased HDL-cholesterol. Gastrointestinal effects occurred frequently in subjects on metformin. CONCLUSION: Both treatments improved insulin sensitivity, but neither reduced visceral fat. Rosiglitazone may increase subcutaneous fat in some individuals.

Adult↗

PubMed2006

Concordance and discordance between two measures of lower extremity function: 400 meter self-paced walk and SPPB.

BACKGROUND AND AIMS: The purpose of the study was to assess the concurrent validity of the 400 meter self-paced walk test (400-m W) against the commonly used short physical performance battery (SPPB). A secondary purpose was to determine whether the 400-m W could better discriminate physical performance among high functioning older adults by examining the distribution of 400-m W scores. METHODS: 101 men and women (80.8+/-0.4 years) were recruited to participate in the study. The 400-mW and SPPB assessed lower extremity function. Lower extremity muscle strength, power, and contraction velocity was assessed using bilateral leg press (LP). Health history was obtained with questionnaire. RESULTS: 400-m W demonstrated moderate correlations with SPPB (Pearson r=0.74; p< 0.001). In 36 high functioning individuals (SPPB score= 10, 11, 12), participants above the median 400-m W performance time (n=20) had more medical conditions (2.8+/-0.4 vs 1.7+/-0.3; p=0.038), more reported falls (0.80+/-0.2 vs 0.19+/-0.1; p=0.016), more medications (3.7+/-0.4 vs 1.8+/-0.4; p=0.001), had lower LP power at 70% of the one repetition maximum (1RM) (336+/-45 W vs 663+/-78 W; p=0.001) and 40% 1RM (329+/-43 W vs 580+/-75 W; p=0.005), and had slower LP contraction velocity at 40% 1RM (77+/-5.5 m/s vs 112+/-8.4 m/s; p=0.001) compared with those below the median (n=16). CONCLUSIONS: A substantial number of apparently well functioning older adults demonstrated some limitations in the ability to walk 400 meters. Use of the 400-m W may be justified to obtain information to better discriminate among high functioning elderly.

Aged↗

PubMed2006

Sex differences in single muscle fiber power in older adults.

PURPOSE: This study was conducted to determine whether differences in power at the single muscle fiber level contribute to sex differences in whole muscle power production in the elderly. METHODS: A total of 16 sedentary older persons (10 women, 6 men), mean age 72 yr, had percutaneous needle biopsy of musculus vastus lateralis. Chemically skinned single muscle fibers were activated with Ca for maximal isometric force measurement (Po). The slack test was performed to determine maximal unloaded shortening velocity (Vo). Force-velocity and power curves were generated via a series of isotonic contractions, allowing measurement of peak power and specific power. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) was used to determine myosin heavy chain composition of single muscle fibers. Whole muscle strength, velocity, and power were measured for knee extension and double leg press. RESULTS: Men had greater whole muscle strength, power, and velocity compared with women. Studied were 274 type I and 33 type IIa single fibers. No significant sex differences were found for fiber size, Po, specific force, Vo, power, or specific power in type I or IIa fibers. CONCLUSIONS: Single muscle fiber quality in older women is equivalent to that in older men and can not explain the differences seen in whole muscle strength, power, or function.

Aged↗

PubMed2006

Creatine monohydrate as a therapeutic aid in muscular dystrophy.

In recent years, dietary supplementation with creatine has been shown to enhance neuromuscular function in several diseases. Recent studies have suggested that creatine can be beneficial in patients with muscular dystrophy and other mitochondrial cytopathies, and may attenuate sarcopenia and facilitate rehabilitation of disuse atrophy. Though the mechanisms are still unknown, creatine has been shown to decrease cytoplasmic Ca2+ levels and increase intramuscular and cerebral phosphocreatine stores, providing potential musculoskeletal and neuroprotective effects.

Calcium↗

PubMed2006

Muscle impairments and behavioral factors mediate functional limitations and disability following stroke.

BACKGROUND AND PURPOSE: Stroke remains the leading cause of disability in the United States. The purposes of this study were to examine whether quantitative measures of muscle strength and power in the involved lower extremity predict functional limitations and to evaluate the contributions of behavioral factors to mediating disability and quality of life in people who have survived a stroke. SUBJECTS AND METHODS: A cross-sectional study design was used, and measurements of muscle impairment, lower-body function, disability, quality of life, and behavioral factors were obtained for 31 community-dwelling volunteers who had experienced a single ischemic stroke in the past 6 to 24 months. RESULTS: Stepwise regression models including impairment and behavioral measures were strong predictors of function, disability, and quality of life. Involved-extremity muscle strength and power and self-efficacy were independently associated with function, whereas depression and self-efficacy were strong predictors of disability and quality of life. DISCUSSION AND CONCLUSION: The findings warrant future studies to determine whether interventions that address muscle strength and power, depressive symptoms, and low self-efficacy effectively improve function, reduce disability, and enhance quality of life in people who have survived a stroke.

Activities of Daily Living↗

PubMed2005

Age-associated decrease in contraction-induced activation of downstream targets of Akt/mTor signaling in skeletal muscle.

In this study, we investigated the effect of age on the association of eukaryotic initiation factor 4E (eIF4E) with eukaryotic initiation factor 4G (eIF4G), as well as the activity of its binding protein (4E-BP1) and the activity of glycogen synthase kinase-3 (GSK-3) after a single bout of rat hindlimb muscle contractile activity elicited by high-frequency electrical stimulation (HFES) of the sciatic nerve. Tibialis anterior (TA) and plantaris (Pla) muscles from adult (Y; 6 mo old) and aged (O; 30 mo old) Fischer 344 x Brown Norway rats were collected immediately or 6 h after HFES. eIF4E-eIF4G association was elevated at 6 h of recovery in TA (1.9 +/- 0.2-fold, P < 0.05) and immediately and 6 h after exercise in Pla (2.1 +/- 0.3- and 2.1 +/- 0.7-fold, P < 0.05) in Y rats. No significant increase was observed in O rats. An increase in 4E-BP1 phosphorylation was observed only 6 h after HFES in TA (5.0 +/- 2.0-fold, P < 0.05) in Y rats. Phosphorylation of GSK-3alpha was increased immediately and 6 h after contraction in TA (1.6 +/- 0.3- and 4.1 +/- 0.8-fold, P < 0.05) and Pla (1.7 +/- 0.2- and 2.1 +/- 0.4-fold, P < 0.05) in Y rats and remained unaffected in O rats. Phosphorylation of GSK-3beta was observed only immediately after HFES in TA (1.5 +/- 0.2-fold, P < 0.05) in Y rats. Overall, eIF4E-eIF4G association and phosphorylation of 4E-BP1 and GSK-3 are increased after HFES in adult, but not in aged, animals. These observations suggest that the anabolic response to muscle stimulation is attenuated with aging and may contribute to the limited capacity of hypertrophy in aged animals.

Aging↗

PubMed2005

The expression of neuregulin and erbB receptors in human skeletal muscle: effects of progressive resistance training.

The neuregulin/erbB-signaling axis contributes to the development and growth of multiple mammalian tissues including skeletal muscle. In this study, we sought to characterize the native expression of this system in human skeletal muscle and test the hypothesis that a program of progressive resistance training (PRT) would regulate the expression of neuregulin (NRG) and its cognate receptors. Twelve healthy-male subjects underwent 8-weeks of lower-extremity PRT and muscle biopsies were performed at baseline and following 1- and 8-weeks of the intervention. PRT resulted in significant gains in skeletal muscle strength without appreciable changes in fiber size or myosin heavy chain (MHC) composition. At baseline, Western Blot analysis demonstrated expression of erbB2, erbB3 and erbB4 receptors and multiple NRG isoforms. Following 1- and 8-weeks of PRT, no changes erbB2, erbB4 or NRG expression were observed. ErbB3 expression, however, was significantly increased at both time points compared to baseline. Double labeling of muscle cross-sections revealed increased expression of erbB3 following PRT was not exclusive to fibers staining positive for MHC IIa. Thus, erbB2, erbB3, erbB4 and multiple NRG isoforms are natively expressed in human skeletal muscle. Following PRT, a significant increase in erbB3 was observed. The ability to detect basal expression and alterations in response to physiologic stimuli merit further studies examining the role of this system in skeletal muscle.

Adult↗

PubMed2005

Identification of a molecular signature of sarcopenia.

Investigating the molecular mechanisms underlying sarcopenia in humans with the use of microarrays has been complicated by low sample size and the variability inherent in human gene expression profiles. We have conducted a study using Affymetrix GeneChips to identify a molecular signature of aged skeletal muscle. The molecular signature was defined as the set of expressed genes that best distinguished the vastus lateralis muscle of young (n = 10) and older (n = 12) male subjects, when a k-nearest neighbor supervised classification method was used in conjunction with a signal-to-noise ratio gene selection method and a holdout cross-validation procedure. The age-specific expression signature was comprised of 45 genes; 27 were upregulated and 18 were downregulated. This signature also correctly classified 75% of the muscle samples from young and older subjects published by an independent laboratory, based on their expression profiles. The signature revealed increased expression of several genes involved in mediating cellular responses to inflammation and apoptosis, including complement component C1QA, Galectin-1, C/EBP-beta, and FOXO3A, among others. The increased expressions of genes that regulate pre-mRNA splicing, localization, and modification of RNA comprise markers of the aging signature. Downregulated genes in the signature were the glutamine transporter SLC38A1, a TRAF-6 inhibitory zinc finger protein, and membrane-bound transcription factor protease S2P, among others. The sarcopenia signature developed here will be useful as a molecular model to judge the effectiveness of exercise and other therapeutic treatments aimed at ameliorating the effects of muscle loss associated with aging.

Adult↗

PubMed2005

The lifestyle interventions and independence for elders (LIFE) pilot study: design and methods.

The LIFE study is a multicenter pilot for a proposed full scale, two-arm randomized controlled trial that will contrast the effect of a physical activity intervention with a successful aging education program on the occurrence of incident major mobility disability (the inability to complete a 400 m walk) or death in at-risk sedentary older adults. Four hundred older adults from 4 clinical sites will be recruited for this purpose. All participants will be followed for at least 1-year; however, we will continue to follow all participants until the final randomized individual has reached the 1-year mark. This will enable us to acquire additional information about maintenance. Additional outcomes will include lower extremity physical performance as well as gait speed over 4 m and 400 m. These latter measures will provide data on the efficacy of the intervention on intermediate endpoints linked to the primary outcome of interest. The goals of the pilot study are to (a) estimate the sample size needed for a full scale trial, (b) examine the consistency of the effects of the physical activity intervention on several continuous measures of physical function, (c) assess the feasibility of recruitment, (d) evaluate study adherence and retention, (d) evaluate the efficacy of a stepped care approach for managing intercurrent illness in this at-risk population, and (e) develop a comprehensive system for monitoring and ensuring participant safety. Other goals of this pilot phase include assessments of health-related quality of life and cost-effectiveness.

Aged↗

PubMed2005

Effect of leg muscle contraction velocity on functional performance in older men and women.

OBJECTIVES: To explore the relationship between impairment (skeletal muscle strength and contraction velocity) and function in community-dwelling older adults. DESIGN: Cross-sectional. SETTING: University-based human physiology laboratory. PARTICIPANTS: One hundred one men and women (aged 75-90). MEASUREMENTS: Muscle strength and contraction velocity during bilateral leg press (LP) were calculated during one-repetition maximum (1RM) and 40% 1RM. A short physical performance battery (SPPB) and gait speed (GS) from a 400-m self-paced walk assessed function. Sex differences in LP strength and contraction velocity (at 40% 1RM) were assessed. The relationship between these variables and function was also examined. RESULTS: Lower extremity strength and contraction velocity were significantly associated with GS (P=.02 and P=.005, respectively) and SPPB (P<.001 and P=.009, respectively) in men only. Contraction velocity, but not muscle strength, was significantly associated with GS (P<.001) and SPPB (P=.02) in women. CONCLUSION: Sex differences exist in the relationship between impairment (muscle strength and contraction velocity) and function. Older men and women may employ different strategies to achieve success on different functional tasks. These findings may have important implications for clinicians practicing geriatric rehabilitation.

Aged↗

PubMed2004

High-intensity resistance training improves muscle strength, self-reported function, and disability in long-term stroke survivors.

BACKGROUND AND PURPOSE: To evaluate the efficacy of supervised high-intensity progressive resistance training (PRT) on lower extremity strength, function, and disability in older, long-term stroke survivors. METHODS: Forty-two volunteers aged 50 years and above, 6 months to 6 years after a single mild to moderate stroke, were randomized into either a control group of upper extremity stretching or a PRT group that received a 12-week supervised high-intensity resistance training program consisting of bilateral leg press (LP), unilateral paretic and nonparetic knee extension (KE), ankle dorsiflexion (DF), and plantarflexion (PF) exercises. Functional performance was assessed using the 6-minute walk, stair-climb time, repeated chair-rise time, and habitual and maximal gait velocities. Self-reported changes in function and disability were evaluated using the Late Life Function and Disability Instrument (LLFDI). RESULTS: Single-repetition maximum strength significantly improved in the PRT group for LP (16.2%), paretic KE (31.4%), and nonparetic KE (38.2%) with no change in the control group. Paretic ankle DF (66.7% versus -24.0%), paretic ankle PF (35.5% versus -20.3%), and nonparetic ankle PF (14.7% versus -13.8%) significantly improved in the PRT group compared with the control. The PRT group showed significant improvement in self-reported function and disability with no change in the control. There was no significant difference between groups for any performance-based measure of function. CONCLUSIONS: High-intensity PRT improves both paretic and nonparetic lower extremity strength after stroke, and results in reductions in functional limitations and disability.

Aged↗

PubMed2004

Contraction-mediated mTOR, p70S6k, and ERK1/2 phosphorylation in aged skeletal muscle.

With age, skeletal muscle experiences substantial atrophy and weakness. Although resistance training can increase muscle size and strength, the myogenic response to exercise and the capacity for muscle hypertrophy in older humans and animals is limited. In the present study, we assessed the ability of muscle contractile activity to activate cellular pathways involved in muscle cell growth and myogenesis in adult (Y; 6 mo old) and aged (O; 30 mo old) Fischer 344 x Brown Norway rats. A single bout of rat hindlimb muscle contractile activity was elicited by high-frequency electrical stimulation (HFES) of the sciatic nerve. Plantaris (Pla) and tibialis anterior (TA) muscles were assayed for mammalian target of rapamycin (mTOR), 70-kDa ribosomal protein S6 kinase (p70(S6K)), and extracellular signal-regulated kinase (ERK) 1/2 phosphorylation and total protein either at baseline, immediately after, or 6 h after HFES. mTOR phosphorylation was elevated in Pla (1.3 +/- 0.3-fold, P < 0.05) immediately after HFES and to a lesser extent 6 h after HFES (0.6 +/- 0.1-fold, P < 0.05) in O rats. Post-HFES, p70(S6K) phosphorylation increased 1.2 +/- 0.3-fold in TA (P < 0.05) and remained elevated 6 h later (0.6 +/- 0.2-fold, P < 0.05) in O rats. ERK phosphorylation was lower in O rats immediately after exercise in both TA (11.1 +/- 2.9 vs. 2.1 +/- 0.5-fold, P < 0.05) and Pla (6.5 +/- 1.5 vs. 1.8 +/- 0.5-fold, P < 0.05) and returned to baseline by 6 h in both Y and O rats. Phosphorylation of mTOR, p70(S6K), and ERK1/2 are increased in skeletal muscle after a single bout of in situ muscle contractile activity in aged animals, and the response is less than that observed in adult animals. These observations suggest that the anabolic response to a single bout of contraction is attenuated with aging and may help explain the reduced capacity for hypertrophy in aged animals.

Aging↗

PubMed2004

Use of phosphocreatine kinetics to determine the influence of creatine on muscle mitochondrial respiration: an in vivo 31P-MRS study of oral creatine ingestion.

Recent human isolated muscle fiber studies suggest that phosphocreatine (PCr) and creatine (Cr) concentrations play a role in the regulation of mitochondrial respiration rate. To determine whether similar regulatory mechanisms are present in vivo, this study examined the relationship between skeletal muscle mitochondrial respiration rate and end-exercise PCr, Cr, PCr-to-Cr ratio (PCr/Cr), ADP, and pH by using (31)P-magnetic resonance spectroscopy in 16 men and women (36.9 +/- 4.6 yr). The initial PCr resynthesis rate and time constant (T(c)) were used as indicators of mitochondrial respiration after brief (10-12 s) and exhaustive (1-4 min) dynamic knee extension exercise performed in placebo and creatine-supplemented conditions. The results show that the initial PCr resynthesis rate has a strong relationship with end-exercise PCr, Cr, and PCr/Cr (r > 0.80, P < 0.001), a moderate relationship with end-exercise ADP (r = 0.77, P < 0.001), and no relationship with end-exercise pH (r = -0.14, P = 0.34). The PCr T(c) was not as strongly related to PCr, Cr, PCr/Cr, and ADP (r < 0.77, P < 0.001-0.18) and was significantly influenced by end-exercise pH (r = -0.43, P < 0.01). These findings suggest that end-exercise PCr and Cr should be taken into consideration when PCr recovery kinetics is used as an indicator of mitochondrial respiration and that the initial PCr resynthesis rate is a more reliable indicator of mitochondrial respiration compared with the PCr T(c).

Adenosine Diphosphate↗

PubMed2004

Impact of muscle power and force on gait speed in disabled older men and women.

BACKGROUND: The purpose of this study was to explore the relationship between muscle power output at different external resistances and performance of functional tasks. The authors hypothesized that power at 40% skeletal muscle 1 repetition maximum (1RM), in which contraction velocity is high, would explain more of the variability in tasks such as level walking than would peak power or 1RM strength, in which contraction velocity is lower. METHODS: Participants were men and women (n = 48; ages 65-91 years) with physical disability as evidenced by 2 or more deficits on the Medical Outcomes Study Short Form physical function subscale or a score of 9 or less on the Established Populations for the Epidemiologic Studies of the Elderly short physical performance battery. Muscle strength (1RM) was measured using a bilateral leg press exercise, and power output was determined by selecting the highest power output from 6 different contraction velocities: 40%, 50%, 60%, 70%, 80%, and 90% 1RM. Functional performance tasks consisted of habitual gait velocity (HGV) and stair climb (SC) and chair rise (CR) performance. Separate linear regression models were fit for each of the 3 dependent variables (SC, CR, HGV) using 1RM strength, power at 70% 1RM, and power at 40% 1RM as independent variables. All models were adjusted for age, body mass, and sex. RESULTS: Lower extremity power at 70% and 40% 1RM demonstrated greater associations with SC and HGV than did 1RM strength, whereas power at 40% 1RM demonstrated similar or stronger associations with all functional tasks compared with 1RM strength. Power at 40% 1RM explained the same or more of the variability in SC (R(2) = .42 [regression coefficient = -.169 +/- .06] vs .43 [-.206 +/- .071]), CR (R(2) = .28 [-.154 +/- .057] vs .24 [-.152 + .070]) and HGV (R(2) = .59 [.214 + .37] vs .51 [.223 +/- .049]) compared with power at 70% 1RM. Power at 40% 1RM explained more of the variability in the lower intensity (HGV) compared with the higher intensity (SC or CR) functions. CONCLUSIONS: Power output at 40% of 1RM explained more of the variability in HGV than did power at 70% 1RM, suggesting that measures such as HGV that require a lower percentage of maximal strength to perform might be more sensitive to differences in contraction velocity. Because HGV is highly predictive of subsequent disability, future studies should evaluate the determinants of muscle power output at low external resistances.

Aged↗

PubMed2004

Increased Velocity Exercise Specific to Task (InVEST) training: a pilot study exploring effects on leg power, balance, and mobility in community-dwelling older women.

OBJECTIVES: To evaluate a dynamic form of weighted vest exercise suitable for home use and designed to enhance muscle power, balance, and mobility. DESIGN: A single-blind, randomized, controlled trial. SETTING: Outpatient exercise research facility situated within an academic long-term care center. PARTICIPANTS: Twenty-one community-dwelling women aged 70 and older with a Short Physical Performance Battery (SPPB) score between 4 and 10 (out of 12). INTERVENTIONS: Subjects were randomized into a progressive resistance-training program using weighted vests for resistance with exercises designed to be specific to mobility tasks and have a component performed at the fastest possible velocity (Increased Velocity Exercise Specific to Task (InVEST), n=11) or a control exercise group (control, n=10), which performed slow-velocity, low-resistance exercise. Both groups exercised three times a week for 12 weeks. MEASUREMENTS: Changes in muscle power, balance, and physical performance were compared. RESULTS: In comparison to control group, InVEST group manifested significant improvements (P<.05) in leg power across measurements obtained at 75% to 90% of the one-repetition maximum. Both groups demonstrated significant improvements in chair stand and SPPB score from baseline, and the InVEST group showed significant improvements in gait speed and chair stand from baseline (P<.05). InVEST produced significantly greater changes in chair stand time than control (P<.05). CONCLUSION: InVEST training appears be an effective means of enhancing leg power and chair rise in this population and is worthy of further investigation as a means of enhancing balance and mobility.

Age Factors↗

PubMed2004

Validation of the Late-Life Function and Disability Instrument.

OBJECTIVES: To assess the concurrent and predictive validity of the Late-Life Function and Disability Instrument (LLFDI). DESIGN: Cross-sectional. SETTING: University-based human physiology laboratory. PARTICIPANTS: One hundred one men and women aged 80.8 +/- 0.4. MEASUREMENTS: A short physical performance battery (SPPB) and a self-paced 400-m walk (400-m W) were used as performance tests of lower extremity function. The LLFDI was used to assess self-reported function and physical disability. Partial correlations adjusted for age and body mass index were used to determine the concurrent and predictive validity of the LLFDI. Statistical significance was accepted at P<.004 using a testwise correction. RESULTS: LLFDI Overall Function scores were moderately associated with the SPPB (r=0.65, P<.001), 400-m W gait speed (r=0.69, P<.001), and measures of lower extremity function. Correlations of the two lower extremity subscores of the LLFDI (correlation coefficient (r)=0.63-0.73, P<.001) were greater than for the LLFDI upper extremity subscores (r=0.19-0.26, P>.004). Performance measures of function predicted disability limitations in the range of r=0.37-0.44 (P<.001) and disability frequency in the range of r=0.16-0.20 (P>.004). CONCLUSION: These findings support the concurrent and predictive validity of the LLFDI. Results support the use of the LLFDI scales as a substitute for physical performance tests when self-report is a preferred data-collection format.

Activities of Daily Living↗

PubMed2004

Use of self-report to predict ability to walk 400 meters in mobility-limited older adults.

OBJECTIVES: To determine whether the ability to walk 400 m could be predicted from self-reported walking habits and abilities in older adults and to develop an accurate self-report measure appropriate for observational trials of mobility when functional measures are impractical to collect. DESIGN: Cross-sectional. SETTING: University-based human physiology laboratory. PARTICIPANTS: One hundred fifty community-dwelling older men and women (mean age+/-standard error= 79.8+/-0.3). MEASUREMENTS: An 18-item questionnaire assessing walking habits and ability was administered to each participant, followed by a 400-m walk test. Ninety-eight (65%) volunteers were able to complete the 400-m walk; 52 (35%) were unable. Logistic regression was performed using response items from a questionnaire as predictors and 400-m walk as the outcome. RESULTS: Three questions (Do you think you could walk one-quarter of a mile now without sitting down to rest. Because of a health or physical problem, do you have difficulty walking 1 mile? Could you walk up and down every aisle of a grocery store without sitting down to rest or leaning on a cart?) were predictive of 400-m walking ability and were included in the model. If participants answered all three questions compatible with the inability to walk 400 m, there was a 91% probability that they were unable to walk 400 m, with a sensitivity of 46% and a specificity of 97%. CONCLUSION: A three-item self-report developed in the study was able to accurately predict mobility disability. The utility of this instrument may be in evaluating self-reported mobility in large observational trials on mobility when functional mobility tasks are impractical to collect.

Aged↗

PubMed2003

Differential activation of mTOR signaling by contractile activity in skeletal muscle.

The cellular mechanisms by which contractile activity stimulates skeletal muscle hypertrophy are beginning to be elucidated and appear to include activation of the phosphatidylinositol 3-kinase signaling substrate mammalian target of rapamycin (mTOR). We examined the time course and location of mTOR phosphorylation in response to an acute bout of contractile activity. Rat hindlimb muscle contractile activity was elicited by high-frequency electrical stimulation (HFES) of the sciatic nerve. Plantaris (Pla), tibialis anterior (TA), and soleus (Sol) muscles from stimulated and control limbs were collected immediately or 6 h after stimulation. HFES resulted in mTOR phosphorylation immediately after (3.4 +/- 0.9-fold, P < 0.01) contractile activity in Pla, whereas TA was unchanged compared with controls. mTOR phosphorylation remained elevated in Pla (3.6 +/- 0.6-fold) and increased in TA (4.6 +/- 0.9-fold, P < 0.05) 6 h after HFES. Interestingly, mTOR activation occurred predominantly in fibers expressing type IIa but not type I myosin heavy chain isoform. Furthermore, HFES induced modest ribosomal protein S6 kinase phosphorylation immediately after exercise in Pla (0.4 +/- 0.1-fold, P < 0.05) but not TA and more markedly 6 h after in both Pla and TA (1.4 +/- 0.4-fold vs. 2.4 +/- 0.3-fold, respectively, P < 0.01). Akt/PKB phosphorylation was similar to controls at both time points. These results suggest that mTOR signaling is increased after a single bout of muscle contractile activity. Despite reports that mTOR is activated downstream of Akt/PKB, in this study, HFES induced mTOR signaling independent of Akt/PKB phosphorylation. Fiber type-dependent mTOR phosphorylation may be a molecular basis by which some fiber types are more susceptible to contraction-induced hypertrophy.

Animals↗