Comparison of Erythrocyte and Skeletal Muscle Creatine Accumulation Following Creatine Loading

2005 ◽  
Vol 15 (1) ◽  
pp. 84-93 ◽  
Author(s):  
David B. Preen ◽  
Brian T. Dawson ◽  
Carmel Goodman ◽  
John Beilby ◽  
Simon Ching
Keyword(s):  
Skeletal Muscle ◽  
Muscle Biopsy ◽  
Vastus Lateralis ◽  
Venous Blood ◽  
Strong Relationship ◽  
Reliable Measure ◽  
Tissue Concentrations ◽  
Muscle Creatine ◽  
The Relationship ◽  
Muscle Biopsies

This study attempted to determine the relationship between creatine (Cr) accumulation in human skeletal muscle and erythrocytes following Cr supplementation. If a strong relationship exists, a blood test might provide a practical, less invasive alternative than muscle biopsy for evaluating cellular Cr accumulation. Eighteen active, but not well-trained males were supplemented with Cr (4 × 5g/d) for 5 d. Muscle biopsies (vastus lateralis) were obtained pre- and post-loading and analyzed for Cr, phosphocreatine (PCr), and total Cr (TCr) content. Venous blood was also drawn at these times to determine erythrocyte Cr concentrations. Muscle Cr, PCr, and TCr concentrations were elevated (P < 0.05) by 39.8%, 7.5%, and 20.1% respectively following supplementation. Erythrocyte Cr concentrations were also elevated (P < 0.01) following the loading period, although to a greater relative degree than tissue concentrations (129.6%). Pre- and post-loading erythrocyte Cr concentrations were poorly and nonsignificantly correlated with that observed in skeletal muscle. Further, loading-mediated increases in erythrocyte Cr concentrations were poorly correlated with elevations in muscle Cr (r = 0.07), PCr (r = 0.06) or TCr (r = 0.04) concentrations. Erythrocyte Cr concentrations can be augmented by 5 d of Cr supplementation, however, this elevation does not reflect that observed in skeletal muscle obtained by muscle biopsy. Consequently, erythrocyte response to Cr loading is not a reliable measure of skeletal muscle Cr/TCr accumulation.

Effect of α-Lipoic Acid Combined with Creatine Monohydrate on Human Skeletal Muscle Creatine and Phosphagen Concentration

2003 ◽  
Vol 13 (3) ◽  
pp. 294-302 ◽  
Author(s):  
Darren G. Burke ◽  
Philip D. Chilibeck ◽  
Gianni Parise ◽  
Mark A. Tarnopolsky ◽  
Darren G. Candow
Keyword(s):  
Skeletal Muscle ◽  
Lipoic Acid ◽  
Human Skeletal Muscle ◽  
Vastus Lateralis ◽  
Creatine Supplementation ◽  
Creatine Monohydrate ◽  
Glucose Disposal ◽  
Creatine Uptake ◽  
Total Creatine ◽  
Muscle Creatine

α-lipoic acid has been found to enhance glucose uptake into skeletal muscle in animal models. Studies have also found that the co-ingestion of carbohydrate along with creatine increases muscle creatine uptake by a process related to insulin-stimulated glucose disposal. The purpose of this study was to determine the effect of α-lipoic acid on human skeletal muscle creatine uptake by directly measuring intramuscular concentrations of creatine, phosphocreatine, and ad-enosine triphosphate when creatine monohydrate was co-ingested with α-lipoic acid. Muscle biopsies were acquired from the vastus lateralis m. of 16 male subjects (18–32 y) before and after the experimental intervention. After the initial biopsy, subjects ingested 20 g · d−1 of creatine monohydrate, 20 g · d−1 of creatine monohydrate + 100 g · d−1 of sucrose, or 20 g · d−1 of creatine monohydrate + 100 g · d−1 of sucrose + 1000 mg · d−1 of α-lipoic acid for 5 days. Subjects refrained from exercise and consumed the same balanced diet for 7 days. Body weight increased by 2.1% following the nutritional intervention, with no differences between the groups. There was a significant increase in total creatine concentration following creatine supplementation, with the group ingesting α-lipoic acid showing a significantly greater increase (p < .05) in phosphocreatine (87.6 → 106.2 mmol · kg−1 dry mass [dm]) and total creatine (137.8 → 156.8 mmol · kg−1 dm). These findings indicate that co-ingestion of α-lipoic acid with creatine and a small amount of sucrose can enhance muscle total creatine content as compared to the ingestion of creatine and sucrose or creatine alone.

A single bout of exercise activates matrix metalloproteinase in human skeletal muscle

2007 ◽  
Vol 102 (6) ◽  
pp. 2346-2351 ◽  
Author(s):  
E. Rullman ◽  
H. Rundqvist ◽  
D. Wågsäter ◽  
H. Fischer ◽  
P. Eriksson ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Matrix Metalloproteinase ◽  
Vastus Lateralis ◽  
Tissue Expression ◽  
Tissue Inhibitor Of Metalloproteinase ◽  
Vastus Lateralis Muscle ◽  
Protein Levels ◽  
Single Bout ◽  
Exercise Induced ◽  
Muscle Biopsies

The aims of this study were 1) to characterize changes in matrix metalloproteinase (MMP), endostatin, and vascular endothelial growth factor (VEGF)-A expression in skeletal muscle in response to a single bout of exercise in humans; and 2) to determine if any exchange of endostatin and VEGF-A between circulation and the exercising leg is associated with a change in the tissue expression or plasma concentration of these factors. Ten healthy males performed 65 min of cycle exercise, and muscle biopsies were obtained from the vastus lateralis muscle at rest and immediately and 120 min after exercise. In the muscle biopsies, measurements of mRNA expression levels of MMP-2, MMP-9, MMP-14, and tissue inhibitor of metalloproteinase; VEGF and endostatin protein levels; and MMP activities were performed. Femoral arterial and venous concentrations of VEGF-A and endostatin were determined before, during, and 120 min after exercise. A single bout of exercise increased MMP-9 mRNA and activated MMP-9 protein in skeletal muscle. No measurable increase of endostatin was observed in the skeletal muscle or in plasma following exercise. A concurrent increase in skeletal muscle VEGF-A mRNA and protein levels was induced by exercise, with no signs of peripheral uptake from the circulation. However, a decrease in plasma VEGF-A concentration occurred following exercise. Thus 1) a single bout of exercise activated the MMP system without any resulting change in tissue endostatin protein levels, and 2) the increased VEGF-A protein levels are due to changes in the skeletal muscle tissue itself. Other mechanisms are responsible for the observed exercise-induced decrease in VEGF-A in plasma.

scholarly journals Cardiovascular and skeletal muscle health with lifelong exercise

2018 ◽  
Vol 125 (5) ◽  
pp. 1636-1645 ◽  
Author(s):  
Kevin J. Gries ◽  
Ulrika Raue ◽  
Ryan K. Perkins ◽  
Kaleen M. Lavin ◽  
Brittany S. Overstreet ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Oxygen Consumption ◽  
Aerobic Exercise ◽  
Muscle Biopsy ◽  
Citrate Synthase ◽  
Vastus Lateralis ◽  
Metabolic Phenotype ◽  
Vastus Lateralis Muscle ◽  
Metabolic Fitness ◽  
Lifelong Exercise

The purpose of this study was to examine the effects of aerobic lifelong exercise (LLE) on maximum oxygen consumption (V̇o2max) and skeletal muscle metabolic fitness in trained women ( n = 7, 72 ± 2 yr) and men ( n = 21, 74 ± 1 yr) and compare them to old, healthy nonexercisers (OH; women: n = 10, 75 ± 1 yr; men: n = 10, 75 ± 1 yr) and young exercisers (YE; women: n = 10, 25 ± 1 yr; men: n = 10, 25 ± 1 yr). LLE men were further subdivided based on intensity of lifelong exercise and competitive status into performance (LLE-P, n = 14) and fitness (LLE-F, n = 7). On average, LLE exercised 5 day/wk for 7 h/wk over the past 52 ± 1 yr. Each subject performed a maximal cycle test to assess V̇o2maxand had a vastus lateralis muscle biopsy to examine capillarization and metabolic enzymes [citrate synthase, β-hydroxyacyl-CoA dehydrogenase (β-HAD), and glycogen phosphorylase]. V̇o2maxhad a hierarchical pattern (YE > LLE > OH, P < 0.05) for women (44 ± 2 > 26 ± 2 > 18 ± 1 ml·kg−1·min−1) and men (53 ± 3 > 34 ± 1 > 22 ± 1 ml·kg−1·min−1) and was greater ( P < 0.05) in LLE-P (38 ± 1 ml·kg−1·min−1) than LLE-F (27 ± 2 ml·kg−1·min−1). LLE men regardless of intensity and women had similar capillarization and aerobic enzyme activity (citrate synthase and β-HAD) as YE, which were 20%–90% greater ( P < 0.05) than OH. In summary, these data show a substantial V̇o2maxbenefit with LLE that tracked similarly between the sexes, with further enhancement in performance-trained men. For skeletal muscle, 50+ years of aerobic exercise fully preserved capillarization and aerobic enzymes, regardless of intensity. These data suggest that skeletal muscle metabolic fitness may be easier to maintain with lifelong aerobic exercise than more central aspects of the cardiovascular system.NEW & NOTEWORTHY Lifelong exercise (LLE) is a relatively new and evolving area of study with information especially limited in women and individuals with varying exercise intensity habits. These data show a substantial maximal oxygen consumption benefit with LLE that tracked similarly between the sexes. Our findings contribute to the very limited skeletal muscle biopsy data from LLE women (>70 yr), and similar to men, revealed a preserved metabolic phenotype comparable to young exercisers.

Effects of an acute exercise bout in hypoxia on extracellular vesicle release in healthy and prediabetic subjects

2021 ◽  
Author(s):  
Geoffrey Warnier ◽  
Estelle De Groote ◽  
Florian A. Britto ◽  
Ophélie Delcorte ◽  
Joshua P. Nederveen ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Acute Exercise ◽  
Vastus Lateralis ◽  
Venous Blood ◽  
Plasma Concentrations ◽  
Exercise Bout ◽  
Multivesicular Body ◽  
International Standards ◽  
Size Exclusion ◽  
Number Of Particles

Purpose: To investigate exosome-like vesicle (ELV) plasma concentrations and markers of multivesicular body (MVB) biogenesis in skeletal muscle in response to acute exercise. Methods: Seventeen healthy (BMI: 23.5±0.5kg·m-2) and fifteen prediabetic (BMI: 27.3±1.2kg·m-2) men were randomly assigned to two groups performing an acute cycling bout in normoxia or hypoxia (FiO2 14.0%). Venous blood samples were taken before (T0), during (T30) and after (T60) exercise and biopsies from m. vastus lateralis were collected before and after exercise. Plasma ELVs were isolated by size exclusion chromatography, counted by nanoparticle tracking analysis (NTA), and characterized according to international standards, followed by expression analyses of canonical ELV markers in skeletal muscle. Results: In the healthy normoxic group, the total number of particles in the plasma increased during exercise from T0 to T30 (+313%) followed by a decrease from T30 to T60 (-53%). In the same group, an increase in TSG101, CD81 and HSP60 protein expression was measured after exercise in plasma ELVs; however, in the prediabetic group, the total number of particles in the plasma was not affected by exercise. The mRNA content of TSG101, ALIX and CD9 were upregulated in skeletal muscle after exercise in normoxia; whereas, CD9 and CD81 were downregulated in hypoxia. Conclusions: ELV plasma abundance increased in response to acute aerobic exercise in healthy subjects in normoxia, but not in prediabetic subjects, nor in hypoxia. Skeletal muscle analyses suggested that this tissue did not likely play a major role of the exercise-induced increase in circulating ELVs.

Progressive increase in human skeletal muscle AMPKα2 activity and ACC phosphorylation during exercise

2002 ◽  
Vol 282 (3) ◽  
pp. E688-E694 ◽  
Author(s):  
T. J. Stephens ◽  
Z.-P. Chen ◽  
B. J. Canny ◽  
B. J. Michell ◽  
B. E. Kemp ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Glycogen ◽  
Human Skeletal Muscle ◽  
Glycogen Content ◽  
Vastus Lateralis ◽  
Moderate Intensity ◽  
Moderate Intensity Exercise ◽  
Western Blots ◽  
Muscle Glycogen Content ◽  
Muscle Creatine

The effect of prolonged moderate-intensity exercise on human skeletal muscle AMP-activated protein kinase (AMPK)α1 and -α2 activity and acetyl-CoA carboxylase (ACCβ) and neuronal nitric oxide synthase (nNOSμ) phosphorylation was investigated. Seven active healthy individuals cycled for 30 min at a workload requiring 62.8 ± 1.3% of peak O2consumption (V˙o 2 peak) with muscle biopsies obtained from the vastus lateralis at rest and at 5 and 30 min of exercise. AMPKα1 activity was not altered by exercise; however, AMPKα2 activity was significantly ( P < 0.05) elevated after 5 min (∼2-fold), and further elevated ( P < 0.05) after 30 min (∼3-fold) of exercise. ACCβ phosphorylation was increased ( P < 0.05) after 5 min (∼18-fold compared with rest) and increased ( P< 0.05) further after 30 min of exercise (∼36-fold compared with rest). Increases in AMPKα2 activity were significantly correlated with both increases in ACCβ phosphorylation and reductions in muscle glycogen content. Fat oxidation tended ( P = 0.058) to increase progressively during exercise. Muscle creatine phosphate was lower ( P < 0.05), and muscle creatine, calculated free AMP, and free AMP-to-ATP ratio were higher ( P < 0.05) at both 5 and 30 min of exercise compared with those at rest. At 30 min of exercise, the values of these metabolites were not significantly different from those at 5 min of exercise. Phosphorylation of nNOSμ was variable, and despite the mean doubling with exercise, statistically significance was not achieved ( P = 0.304). Western blots indicated that AMPKα2 was associated with both nNOSμ and ACCβ consistent with them both being substrates of AMPKα2 in vivo. In conclusion, AMPKα2 activity and ACCβ phosphorylation increase progressively during moderate exercise at ∼60% of V˙o 2 peak in humans, with these responses more closely coupled to muscle glycogen content than muscle AMP/ATP ratio.

Effects of 7 wk of endurance training on human skeletal muscle metabolism during submaximal exercise

2004 ◽  
Vol 97 (6) ◽  
pp. 2148-2153 ◽  
Author(s):  
Paul J. LeBlanc ◽  
Krista R. Howarth ◽  
Martin J. Gibala ◽  
George J. F. Heigenhauser
Keyword(s):  
Skeletal Muscle ◽  
Endurance Training ◽  
Glycogen Phosphorylase ◽  
Human Skeletal Muscle ◽  
Vastus Lateralis ◽  
Muscle Metabolism ◽  
Allosteric Modulators ◽  
Before And After ◽  
First Time ◽  
Muscle Biopsies

This is the first study to examine the effects of endurance training on the activation state of glycogen phosphorylase (Phos) and pyruvate dehydrogenase (PDH) in human skeletal muscle during exercise. We hypothesized that 7 wk of endurance training (Tr) would result in a posttransformationally regulated decrease in flux through Phos and an attenuated activation of PDH during exercise due to alterations in key allosteric modulators of these important enzymes. Eight healthy men (22 ± 1 yr) cycled to exhaustion at the same absolute workload (206 ± 5 W; ∼80% of initial maximal oxygen uptake) before and after Tr. Muscle biopsies (vastus lateralis) were obtained at rest and after 5 and 15 min of exercise. Fifteen minutes of exercise post-Tr resulted in an attenuated activation of PDH (pre-Tr: 3.75 ± 0.48 vs. post-Tr: 2.65 ± 0.38 mmol·min−1·kg wet wt−1), possibly due in part to lower pyruvate content (pre-Tr: 0.94 ± 0.14 vs. post-Tr: 0.46 ± 0.03 mmol/kg dry wt). The decreased pyruvate availability during exercise post-Tr may be due to a decreased muscle glycogenolytic rate (pre-Tr: 13.22 ± 1.01 vs. post-Tr: 7.36 ± 1.26 mmol·min−1·kg dry wt−1). Decreased glycogenolysis was likely mediated, in part, by posttransformational regulation of Phos, as evidenced by smaller net increases in calculated muscle free ADP (pre-Tr: 111 ± 16 vs. post-Tr: 84 ± 10 μmol/kg dry wt) and Pi (pre-Tr: 57.1 ± 7.9 vs. post-Tr: 28.6 ± 5.6 mmol/kg dry wt). We have demonstrated for the first time that several signals act to coordinately regulate Phos and PDH, and thus carbohydrate metabolism, in human skeletal muscle after 7 wk of endurance training.

Short-term training increases human muscle MCT1 and femoral venous lactate in relation to muscle lactate

1998 ◽  
Vol 274 (1) ◽  
pp. E102-E107 ◽  
Author(s):  
A. Bonen ◽  
K. J. A. McCullagh ◽  
C. T. Putman ◽  
E. Hultman ◽  
N. L. Jones ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Vastus Lateralis ◽  
Venous Blood ◽  
Maximal Oxygen Consumption ◽  
Bicycle Ergometer ◽  
Monocarboxylate Transporter ◽  
Short Term ◽  
Bicycle Ergometry ◽  
Muscle Lactate ◽  
Monocarboxylate Transporter 1

We examined the effects of increasing a known lactate transporter protein, monocarboxylate transporter 1 (MCT1), on lactate extrusion from human skeletal muscle during exercise. Before and after short-term bicycle ergometry training [2 h/day, 7 days at 65% maximal oxygen consumption (V˙o 2 max)], subjects ( n = 7) completed a continuous bicycle ergometer ride at 30%V˙o 2 max (15 min), 60%V˙o 2 max (15 min), and 75% V˙o 2 max (15 min). Muscle biopsy samples (vastus lateralis) and arterial and femoral venous blood samples were obtained before exercise and at the end of each workload. After 7 days of training the MCT1 content in muscle was increased (+18%; P < 0.05). The concentrations of both muscle lactate and femoral venous lactate were reduced during exercise ( P < 0.05) that was performed after training. High correlations were observed between muscle lactate and venous lactate before training ( r = 0.92, P < 0.05) and after training ( r = 0.85, P < 0.05), but the slopes of the regression lines between these variables differed markedly. Before training, the slope was 0.12 ± 0.01 mM lactate ⋅ mmol lactate−1 ⋅ kg muscle dry wt−1, and this was increased by 33% after training to 0.18 ± 0.02 mM lactate ⋅ mmol lactate−1 ⋅ kg muscle dry wt−1. This indicated that after training the femoral venous lactate concentrations were increased for a given amount of muscle lactate. These results suggest that lactate extrusion from exercising muscles is increased after training, and this may be associated with the increase in skeletal muscle MCT1.

Impaired expression and insulin-stimulated phosphorylation of Akt-2 in muscle of obese patients with atypical diabetes

2004 ◽  
Vol 287 (1) ◽  
pp. E8-E15 ◽  
Author(s):  
Aidar R. Gosmanov ◽  
Guillermo E. Umpierrez ◽  
Ana H. Karabell ◽  
Ruben Cuervo ◽  
Donald B. Thomason
Keyword(s):  
Skeletal Muscle ◽  
Protein Expression ◽  
Insulin Therapy ◽  
Vastus Lateralis ◽  
Vastus Lateralis Muscle ◽  
Mammalian Skeletal Muscle ◽  
Obese Patients ◽  
Physiological Concentration ◽  
Atypical Diabetes ◽  
Muscle Biopsies

Although a pharmacological dose of insulin produces a dramatic increase in phosphorylation and activity of Akt isoforms 1 and 2 in mammalian skeletal muscle, few studies have examined the effect of physiological concentrations of insulin on the phosphorylation of Akt-1 and -2 in normal and diabetic tissue. This study examined the patterns of insulin-stimulated Akt isoform phosphorylation and protein expression in muscle biopsies obtained from obese patients with atypical diabetes immediately after a hyperglycemic crisis and again after near-normoglycemic remission. In obese patients with new-onset diabetes mellitus presenting with hyperglycemic crisis (plasma glucose 30.5 ± 4.8 mM), in vitro stimulation of vastus lateralis muscle biopsies with 100 μU/ml (0.6 nM) insulin increased insulin receptor phosphorylation threefold and Akt-1 phosphorylation on Ser473 twofold, whereas Akt-2 phosphorylation was not stimulated. After 10-wk intensive insulin therapy that led to near-normoglycemic remission and discontinuation of insulin therapy, both Akt-2 expression and insulin-stimulated Akt-2 Ser474 phosphorylation doubled. Hyperglycemic crisis did not affect insulin-stimulated threonine phosphorylation of either Akt-1 or Akt-2. The decreased Akt-2 expression at presentation was accompanied by reduced GLUT4 protein expression and increased expression of enzymes counterregulatory to insulin action. Thus a physiological concentration of insulin stimulated Akt-1 and Akt-2 phosphorylation in human skeletal muscle in the absence of hyperglycemia, but Akt-2 expression and stimulation appeared to be impaired in muscle of obese patients with atypical diabetes presenting with severe hyperglycemia.

scholarly journals Optimization of the pre-analytical stage of material processing for histochemical examination of skeletal muscle biopsies in the diagnosis of neuromuscular diseases

2019 ◽  
Vol 9 (2) ◽  
pp. 21-29
Author(s):  
A. M. Sycheva ◽  
V. D. Nazarova ◽  
S. V. Lapin ◽  
M. G. Rybakova ◽  
D. I. Rudenko
Keyword(s):  
Skeletal Muscle ◽  
Muscle Biopsy ◽  
Morphological Changes ◽  
Clinical Manifestations ◽  
Neuromuscular Diseases ◽  
Optimal Method ◽  
Tissue Samples ◽  
Important Place ◽  
Skeletal Muscle Biopsy ◽  
Muscle Biopsies

Diagnosis of neuromuscular diseases is complicated by the variety of clinical manifestations and requires the use of additional methods, an important place among which is the pathomorphological study of skeletal muscle biopsy. Despite the fact that the procedure for taking a muscle biopsy is not technically difficult, to obtain informative material a multitude of conditions must be observed at the stages of pre-analytical processing of the obtained tissue samples. Violation of the technology of taking, storing and fixing the material contributes to the formation of artifacts that limit the possibilities for further analysis of the morphological changes in tissue biopsy. A comparison was made of the effectiveness of various methods for cryoprocessing of muscle tissue samples and the manufacture of histological specimens with a subsequent assessment of morphological changes. As a result, the main causes of artifacts were identified. The optimal method for processing muscle biopsy specimens is indicated, which makes it possible to prevent the appearance of artifacts as much as possible and to ensure the preservation of tissue for research.

scholarly journals Calcium and strontium contractile activation properties of single skinned skeletal muscle fibres from elderly women 66-90 years of age

2021 ◽  
Author(s):  
Sue M Ronaldson ◽  
George D Stephenson ◽  
Stewart I Head
Keyword(s):  
Skeletal Muscle ◽  
Elderly Women ◽  
Vastus Lateralis ◽  
Muscle Fibres ◽  
Vastus Lateralis Muscle ◽  
Type I ◽  
Lateralis Muscle ◽  
Slow Twitch ◽  
Skeletal Muscle Fibres ◽  
Muscle Biopsies

The single skinned muscle fibre technique was used to investigate Ca2+- and Sr2+- activation properties of skeletal muscle fibres from elderly women (66-90 years). Muscle biopsies were obtained from the vastus lateralis muscle. Three populations of muscle fibres were identified according to their specific Sr2+- activation properties: slow-twitch (type I) fast-twitch (type II) and hybrid (type I/II) fibres. All three fibre types were sampled from the biopsies of 66 to 72 years old women, but the muscle biopsies of women older than 80 years yielded only slow-twitch (type I) fibres. The proportion of hybrid fibres in the vastus lateralis muscle of women of circa 70 years of age (24%) was several-fold greater than in the same muscle of adults (<10%), suggesting that muscle remodelling occurs around this age. There were no differences between the Ca2+- and Sr2+- activation properties of slow-twitch fibres from the two groups of elderly women, but there were differences compared with muscle fibres from adults with respect to sensitivity to Ca2+, steepness of the activation curves, and characteristics of the fibre-type dependent phenomenon of spontaneous force oscillations (SOMO) occurring at sub-maximal levels of activation. The maximal Ca2+ activated specific force from all the fibres collected from the seven old women use in the present study was significantly lower by 20% than in the same muscle of adults. Taken together these results show there are qualitative and quantitative changes in the activation properties of the contractile apparatus of muscle fibres from the vastus lateralis muscle of women with advancing age, and that these changes need to be considered when explaining observed changes in womens mobility with aging.

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