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Metabolism| August 01 2003
Impact of Aerobic Exercise Training on Age-Related Changes in Insulin Sensitivity and Muscle Oxidative Capacity
Kevin R. Short;
Kevin R. Short
1Department of Internal Medicine, Division of Endocrinology, Mayo Clinic, Rochester, Minnesota
Janet L. Vittone;
Janet L. Vittone
2Department of General Internal Medicine, Mayo Clinic, Rochester, Minnesota
Maureen L. Bigelow;
Maureen L. Bigelow
David N. Proctor;
David N. Proctor
3Department of Anesthesiology, Mayo Clinic, Rochester, Minnesota
Robert A. Rizza;
Robert A. Rizza
Jill M. Coenen-Schimke;
Jill M. Coenen-Schimke
K. Sreekumaran Nair
Address correspondence and reprint requests to K. Sreekumaran Nair, PhD, Endocrinology Research Unit, 5–194 Joseph, Mayo Clinic, 200 First St. SW, Rochester, MN 55905. E-mail: nair.sree@mayo.edu
Diabetes 2003;52(8):1888–1896
https://doi.org/10.2337/diabetes.52.8.1888
Kevin R. Short, Janet L. Vittone, Maureen L. Bigelow, David N. Proctor, Robert A. Rizza, Jill M. Coenen-Schimke, K. Sreekumaran Nair; Impact of Aerobic Exercise Training on Age-Related Changes in Insulin Sensitivity and Muscle Oxidative Capacity. Diabetes 1 August 2003; 52 (8): 1888–1896. https://doi.org/10.2337/diabetes.52.8.1888
Insulin resistance increases and muscle oxidative capacity decreases during aging, but lifestyle changes—especially physical activity—may reverse these trends. Here we report the effect of a 16-week aerobic exercise program (n = 65) or control activity (n = 37) performed by men and women aged 21–87 years on insulin sensitivity and muscle mitochondria. Insulin sensitivity, measured by intravenous glucose tolerance test, decreased with age (r = −0.32) and was related to abdominal fat content (r = −0.65). Exercise increased peak oxygen uptake (Vo2peak; 10%), activity of muscle mitochondrial enzymes (citrate synthase and cytochrome c oxidase, 45–76%) and mRNA levels of mitochondrial genes (COX4, ND4, both 66%) and genes involved in mitochondrial biogenesis (PGC-1α, 55%; NRF-1, 15%; TFAM, 85%). Exercise also increased muscle GLUT4 mRNA and protein (30–52%) and reduced abdominal fat (5%) and plasma triglycerides (25%). None of these changes were affected by age. In contrast, insulin sensitivity improved in younger people but not in middle-aged or older groups. Thus, the muscle mitochondrial response to 4 months of aerobic exercise training was similar in all age-groups, although the older people did not have an improvement in insulin sensitivity.
The number of people with type 2 diabetes and impaired glucose tolerance is rapidly increasing (1,2). Key factors contributing to this increase in diabetes include age, obesity, and sedentary lifestyle (3–8). Exercise is a readily available intervention that can increase insulin action (9–14) and prevent the onset of diabetes (15–18). An important question is whether the effects of aerobic exercise on insulin action are diminished with advancing age. A recent study reported that a vigorous 7-day exercise program increased insulin sensitivity and muscle glucose transporter (GLUT4) content by a similar amount in younger (22 years) and older (61 years) people (12). However, current health and fitness guidelines for healthy adults recommend exercising at more moderate intensities at least 3 days per week over long periods (19). Thus, the first purpose of the current study was to determine whether a 4-month program of bicycle training that could be readily followed by most elderly individuals would lead to a similar improvement in insulin sensitivity in men and women across a wide age span.
Skeletal muscle is the major site of insulin-mediated glucose disposal and is implicated in the pathogenesis of insulin resistance and diabetes (20,21). Several pieces of evidence suggest that insulin action may be related to the oxidative capacity of skeletal muscle. First, aerobic exercise training improves both insulin sensitivity and activity of oxidative enzymes in muscle (22,23). Second, people who are obese and insulin resistant or have type 2 diabetes tend to have lower activity of muscle oxidative enzymes (24,25). Third, insulin infusion preferentially stimulates the synthesis rate of mitochondrial proteins in skeletal muscle (26) and increases the mRNA abundance genes associated with mitochondria and glucose metabolism (27,28). Fourth, recent work has shown that genes for mitochondrial proteins and the primary glucose transporter in muscle, GLUT4, are regulated by common signals, including elevations in cytosolic calcium (29,30) and the transcriptional coactivator PGC-1α (peroxisome proliferator-activated receptor [PPAR]-γ coactivator 1α) (31). Muscle mitochondrial function and gene expression are reduced in aging muscle, but the underlying cause and the relationship to insulin action are not yet understood (32–34). The second purpose of this study, therefore, was to measure the effect of age and exercise training on the gene expression of PGC-1α, GLUT4, and mitochondrial genes and nuclear transcription factors that regulate mitochondrial genes, including PGC-1α, nuclear respiratory factor (NRF)-1, and mitochondrial transcription factor A (TFAM). We tested the hypothesis that a moderate exercise program results in equivalent improvements in insulin sensitivity, GLUT4 expression, and mitochondrial genes and function in individuals whose age ranged between 22 and 87 years.
Participants.
Healthy men and women who exercised <30 min twice per week during the previous 9 months were recruited. Health status was assessed by medical history, physical exam, blood chemistries (liver enzymes, creatinine, electrolytes, and glucose), complete blood count, urinalysis, and electrocardiogram. Exclusion criteria included tobacco use, β-blockers, diabetes or other endocrine disorders, and debilitating chronic illness. Forty-nine women and 41 men between the ages of 21 and 87 years met these criteria and were enrolled after providing written and oral consent. Characteristics of the participants are shown in Table 1. Participants gave their informed oral and written consent before any tests were performed. The Mayo Foundation Institutional Review Board approved the study.
Study protocol.
Participants were randomized to either a 16-week aerobic control or exercise program. A similar 5-day protocol was completed at baseline and again within a week of completing the training or control phases. During each study period, a weight-maintaining diet (55:30:15% carbohydrate, fat, and protein, respectively) was provided for the first 4 days. On the morning of day 4, subjects were admitted to the General Clinical Research Center (GCRC) following an overnight fast. Insulin sensitivity and body composition were then measured. The following morning (day 5) blood and muscle biopsy samples from the vastus lateralis (32,35) were obtained.
The exercise program was performed on a stationary bicycle. Training started with three sessions per week, lasting 20 min each, at an intensity eliciting 70% of maximal heart rate. Intensity, duration, and number of sessions were gradually increased so that the final month of training consisted of four sessions per week at 80% of maximal heart rate for 40 min. Exercise specialists supervised each session and recorded heart rates. Compliance with the target workloads and number of sessions was >90%. The exercise protocol was completed by 41 of 47 participants originally assigned. The control group was taught a series of flexibility exercises and encouraged to perform them at home while maintaining their regular lifestyle. Follow-up tests were available for 37 of the 43 people in the control group. Subsequently, 24 control group members opted to complete the exercise program, yielding a total of 65 people studied before and after exercise training.
Because the goal of the study was to examine effects of the exercise program, participants were instructed to maintain body weight. Weight was recorded weekly, and the GCRC dietary staff provided further guidance if weight changed >2%. Only one person in the exercise group discontinued the study because of excessive weight loss.
Procedures.
A standard treadmill stress test was performed initially to assure cardiovascular health and was followed on another day with measurement of peak oxygen uptake (Vo2peak) on a bicycle ergometer (36). Expired gases, heart rate, and blood pressure were continuously monitored throughout the tests (36). The posttraining assessment was made within 3 days of the completion of the last training bout.
Insulin sensitivity (SI) was determined using an intravenous glucose tolerance test (37). Posttraining tests were performed 4 or 5 days after the last exercise session (this variation was unavoidable due to scheduling availability). There were no systematic differences across sex or age in the retesting schedule. Glucose (0.3 g/kg) and insulin (0.03 units/kg) were intravenously injected at 0 and 20 min, respectively. Fifteen blood samples were obtained between 0 and 180 min. SI was calculated using minimal model analysis software (MINMOD, version 2.0).
Fat and fat-free mass were determined by dual X-ray absorptiometry (Lunar DPX-L, Madison, WI). Abdominal fat was measured using a single-slice (6-mm thickness) computed tomography scan (Imatron C-150, San Francisco, CA) at the level of the L4–L5 intervertebral space. Total and subcutaneous abdominal fat areas were estimated by manual planimetry using custom software (38). Visceral fat area was calculated as the difference between total and subcutaneous fat areas.
Plasma insulin was measured with a two-site immunoenzymatic assay (Access; Beckman Instruments, Chaska, MN). Glucose was measured with a Beckman Glucose Analyzer (Beckman Instruments, Porterville, CA). Nonesterified free fatty acids (NEFAs) were measured using an enzymatic colorimetric assay (NEFA C; Wako Chemicals, Richmond, VA).
A real-time quantitative PCR system (PE Biosystems, Foster City, CA) was used to measure the abundance of selected mRNAs in muscle tissue (35). Transcripts quantified included GLUT4, NRF-1, PGC-1α, TFAM, and two subunits of mitochondrial respiratory chain proteins. The mitochondrial mRNAs were cytochrome c oxidase subunit 4 (COX4), a nuclear gene encoding part of complex IV, and NADH-dehydrogenase subunit 4 (ND4), a mitochondrial-DNA gene encoding part of complex I. RNA was extracted from skeletal muscle of individual subjects by Trizol method (Life Technologies, Gaithersburg, MD), treated with DNase (Life Technologies), and then reverse-transcribed using the TaqMan Reverse Transcription Reagents (PE Biosystems).
The following primers and probes for human genes were used: GLUT4 (designed from GenBank Accession number M20747 sequence) forward primer: CATTGGTATCATCTCT CAGTGGCT, reverse primer: AGCACCGCCAGGACATTG, probe: ACCAGCATGGCCCT TTTCCTTC; NRF-1 (GenBank accession no. XM011548) forward primer: GAGTGATG TCCGCACAGAAGAG, reverse primer: TTATAACAGTTTTTAACTATGGTCCGTAGTG, probe: TGGGTCCATGAAACCCTCTGCTT; PGC-1α (GenBank accession no. AF106698) forward primer: AGATCGCCCTACAGCCGTC, reverse primer: TCTTCAGCCTCTCGTGCTGA, probe: ATTCCTCGTAGCTGTCATACCTGGGC; TFAM (GenBank accession no. M62810) forward primer: TGTGCACCGGCTGTGG, reverse primer: TGGACAACTTGCCAAGACAGAT, probe: AGTCGACTGCGCTCCCCCTT; COX4 (GenBank accession no. XM008055) forward primer: CCTCCTGGAGCAGCCTCTC, reverse primer: TCAGCAAAGCTCTCCTTGA ACTT, probe: TGCGATACAACTCGACTTTCTCATCCAT; ND4 (GenBank accession no. NC 001807) forward primer: CCCCATTCTCCTCCTATCCC, reverse primer: TTTTTTTTTTTT-TTTTTTTTTTTTTTAAGAG, probe: CAACCCCGACATCATTACCGGGT. The probes for nuclear genes were designed to span exon boundaries to ensure no amplification of contaminating DNA. Because the mitochondrial genome does not contain introns, the reverse primer for ND4 was designed to target several of the final nucleotides specific to the gene as well as a string of the poly-A tail that is present only in the mRNA. Samples were run in triplicate and quantified by normalizing the target signal for the 28S rRNA signal in each sample.
Activities of two mitochondrial enzymes, citrate synthase and cytochrome c oxidase, were measured in muscle homogenates as previously described (32).
Abundance of GLUT4 protein in muscle was determined by Western blotting. Muscle samples were homogenized in a buffer containing 250 mmol/l sucrose, 20 mmol/l HEPES, and 1 mmol/l EDTA, pH 7.4, containing 1 μg/ml leupeptin, 10 μg/ml aprotinin, and 2 mmol/l phenylmethylsulfonyl fluoride, then centrifuged at 100,000g for 60 min. Pellets were resuspended in phosphate buffer containing 1% Triton X-100 and centrifuged at 14,000g for 20 min. The resulting supernatants, containing membrane proteins, were separated on 10% polyacrylamide gels (BioRad Laboratories, Hercules, CA). Proteins were transferred to polyvinylidene difluoride membranes and incubated overnight with a primary antibody against GLUT4 (Biogenesis, Brentwood, NH). An enhanced chemiluminescent detection system (Amersham Biosciences, Piscataway, NJ), followed by digital imaging and densitometry (ImageStation 1000; Eastman Kodak Scientific Imaging, Rochester, NY), was used to quantify the relative abundance of GLUT4 in individual samples.
Data are reported as means ± SE. Differences between men and women and between pre- and posttesting within groups were analyzed using unpaired and paired t tests, respectively. Pearson correlation coefficients were used to measure association among selected variables. Multiple regression analysis was used to determine the relationship of age, body composition, and other variables to insulin sensitivity. P < 0.05 was considered statistically significant.
Physical characteristics and body composition.
The baseline physical characteristics of the participants are given in Table 1, and univariate correlations between these variables and age are listed in Table 2. Although BMI was similar among age-groups, fat-free mass decreased with age and total body fat and abdominal fat increased with age. Subcutaneous abdominal fat also tended to increase with age, but this change was more variable. Exercise resulted in statistically significant reductions in body weight (0.7%), BMI (0.7%), abdominal fat (5.3%), and waist circumference (1.9%) (Table 3). The loss of abdominal fat occurred equally in the visceral and subcutaneous compartments. Except for a small but significant increase in waist size (Table 3), the physical characteristics of the control group did not change during the study.
Aerobic capacity.
At baseline, Vo2peak declined linearly with age from a mean of 50.0 ± 1.0 ml · kg−1 FFM · min−1 in 20- to 30-year-olds to 19.7 ± 1.1 in those ≥70 years (r = 0.82, P < 0.001). The rate of decline was 7.5% per decade. There was no change in Vo2peak in control subjects (Table 3), whereas the exercise program increased Vo2peak by 9.5% (P < 0.001). This response to exercise training was similar in men and women of all ages.
Insulin sensitivity.
SI declined ∼8% per decade in both men and women (P < 0.01). When plotted against age, however, the residual errors for SI were not uniform for either men or women. For this reason, linear modeling of SI was performed after log transformation. The transformed SI was 16% higher in women (P < 0.05) but did not prevent the pooled data from both sexes from being fit by a single line, since the difference was not affected by age (Fig. 1). Univariate correlations between SI (after log transformation) and other variables are listed in Table 2. SI was more closely related to abdominal fat and fasting insulin levels than age (Fig. 1). Like SI, insulin values were also log transformed because of nonuniform distribution.
Multiple regression analyses were used to determine the effects of age, adiposity, and other parameters on SI at baseline. Men and women were analyzed separately. Using step-wise (step-up) regression, only two variables with significant individual contributions were entered into the model for men, namely total abdominal fat area and triglycerides. This model had a multiple R2 of 0.57 and an adjusted R2 of 0.54. When a step-down approach was used for men, total abdominal fat and insulin were retained in the model (multiple R2 = 0.55, adjusted R2 = 0.51). In women, both the step-up and step-down models had a single variable, total abdominal fat area, with a multiple R2 of 0.39 and adjusted R2 of 0.37. Combining men and women in the regression analysis yielded a model with total abdominal fat and insulin as predictors (multiple R2 = 0.48, adjusted R2 = 0.47). Age made a significant contribution to these models only if total abdominal fat and/or insulin were intentionally left out (data not shown).
Exercise training increased insulin sensitivity by an average of 26% (Table 3). However, the response to training (absolute change) was inversely related to age in men and women (Fig. 2). When separated into younger (20−39 years), middle-aged (40–59 years), and older (≥60 years) groups, the posttraining SI increased 72% for younger (5.77 ± 0.73 vs. 9.92 ± 1.36; P < 0.001) and 20% for middle-aged (5.42 ± 0.68 vs. 6.52 ± 0.82; P = 0.11) and decreased 5% for older (3.90 ± 0.44 vs. 3.71 ± 0.53; P = 0.42) people. The response of SI to training was not related to changes in Vo2peak, body composition, muscle metabolic parameters, or any other variables, besides age. When the SI values in the exercise group were expressed as a percentage change from baseline, the negative relationship with age remained statistically significant in women but not in men (Fig. 2). This difference between men and women was due to the strong influence of three men over 40 years of age who began the study with low SI values and had small absolute changes that represented high percentage changes. When considered separately, the percentage change in SI in exercising young men (41 ± 19% for n = 6; P = 0.08 vs. zero) was less than that of young women (116 ± 27% for n = 9; P < 0.01 vs. zero) but stands in contrast to the middle-aged and older groups who showed no trends toward a positive change in SI. Thus, the age-dependent increase in SI after training appears to be present in men and women when considered as either absolute or percentage change.
GLUT4.
GLUT4 mRNA levels did not differ with age among the participants (Fig. 3). After the exercise training program, GLUT4 mRNA levels were elevated by 52% (Table 3), and no effect of either age or sex on the response to exercise was evident. GLUT4 protein levels were measured on a subset of younger (n = 9) and older (n = 11) persons because of limited availability of muscle samples. GLUT4 protein abundance (in arbitrary units) was not significantly different between the younger (5.71 ± 0.41 AU) and older (4.67 ± 0.49 AU) group at baseline. In younger and older exercisers, protein levels were increased 20–40% to 6.83 ± 0.72 and 6.64 ± 0.62 AU, respectively (P < 0.02), with no difference between age groups.
Mitochondrial enzyme activities and gene transcripts.
At baseline, activity of COX declined with age (5% per decade) (Table 2). Citrate synthase activity declined with age in women (4% per decade) (Table 2) but not in men. The exercise program increased COX and citrate synthase activities by 87 and 46%, respectively (Table 3). Enzyme changes with training were not related to either age or sex.
Transcript levels of COX4 and ND4 followed similar patterns to one another, as they both declined significantly with age (Fig. 3) and increased 65–67% with aerobic exercise training (Table 4). These responses to training were not affected by either age or sex. The abundance of mRNAs encoding PCG-1α, NRF-1, and TFAM was unrelated to age at baseline (Fig. 4). Exercise training increased PGC-1α, NRF-1, and TFAM transcript levels by 55, 15, and 85%, respectively, but there was no interaction between age and the training response (Table 4). PGC-1 mRNA levels at baseline were positively associated (P < 0.01) with abundance of NRF-1 (r = 0.67), TFAM (r = 0.53), GLUT4 (r = 0.46), and COX4 (r = 0.40) mRNA. The change in PGC-1α mRNA after training was associated with the change in NRF-1 (r = 0.40, P < 0.01), but not with the changes in TFAM, GLUT4, or COX4.
Plasma lipids, glucose, and insulin.
Total cholesterol increased from 4.24 ± 0.18 mmol/l in 20- to 30-year-olds to 5.54 ± 0.27 in people over 70 years (P < 0.025), whereas HDL and LDL cholesterol levels did not change with age (Table 2). Cholesterol levels were not significantly altered by exercise training (Table 3). Triglyceride (134 ± 15 mg/dl, 20–30 years; 160 ± 15, ≥70 years) and nonesterified fatty acid (485 ± 34 μmol/l, 20–30 years; 587 ± 27, ≥70 years) levels both increased with age (Table 2). Exercise training lowered fasting plasma triglycerides 23% and nonesterified fatty acids 6% (Table 3). Age and sex did not affect these responses.
Fasting glucose levels increased 2% per decade in men and women, whereas insulin increased 13% per decade in women but did not change with age in men (Table 2). Fasting glucose and insulin were positively related (P < 0.01) to abdominal fat (r = 0.56 and 0.65, respectively). Men had higher (P < 0.01) plasma glucose (5%) and insulin (16%) than women. Overall, exercise training did not alter fasting glucose or insulin concentrations (Table 3). When separated into three age-groups, however, fasting insulin levels were significantly reduced from pre- to postexercise in middle-aged people (age 40–59 years, 36 ± 3 vs. 31 ± 3 pmol/l; P = 0.020) and showed a tendency to decline in older people (≥60 years, 44 ± 5 vs. 35 ± 3 pmol/l; P = 0.098). Fasting insulin did not change in younger exercisers (20–39 years old, 32 ± 5 vs. 37 ± 7 pmol/l; P = 0.40). Fasting glucose levels were unchanged in any age-group.
This study examined the effect of a 4-month moderate-intensity aerobic exercise program on insulin sensitivity and muscle mitochondrial biogenesis in people between the ages of 22 and 87 years. In agreement with previous reports, insulin sensitivity declined with age (5–8) but improved with exercise training (9–14). A key finding of the current study is that the increment in insulin sensitivity due to exercise training was present in younger people but not in middle-age and older groups. Several potential factors that might explain the age-dependent change in insulin action with exercise were examined. Abdominal adiposity (which was the best correlate with insulin sensitivity at baseline) and plasma triglycerides were decreased by exercise. In skeletal muscle, glucose transporter mRNA and protein levels were increased, and mitochondrial biogenesis was evident from increased activity of mitochondrial enzymes and higher levels of mitochondrial protein mRNAs. These changes occurred in men and women across the age span. Thus, insulin sensitivity was the only variable that demonstrated an age-dependent response to exercise training.
Insulin-mediated glucose transport in muscle depends on the content and function of GLUT4 (21). Work by Houmard et al. (6) suggested that the age-related decline in insulin action might be due in part to a lower abundance of GLUT4 protein in muscle. Subsequently, it was reported that short-term vigorous training elevated GLUT4 protein content and insulin sensitivity in young and old people (12). In the current study, we found that muscle GLUT4 mRNA and protein levels did not change with age in previously untrained people. Exercise training resulted in increased muscle content of GLUT4 mRNA and protein, but this increment did not differ with age. Thus, in the present study, muscle GLUT4 abundance does not explain the age-related decline in insulin sensitivity or the age-dependent response to exercise training. One possibility is that despite normal GLUT4 content in older muscle, the insulin-mediated trafficking of GLUT4 to the sarcolemma or its inherent function is somehow impaired (20,21). At present, the interaction of age and exercise status on GLUT4 trafficking and transport function is unknown. This is an important question that should be addressed in future work.
The activity of oxidative enzymes is reduced in skeletal muscle from older people (32,34,39) and can contribute to reductions in Vo2peak and the ability to sustain muscular activity. In turn, this could potentially contribute to insulin resistance by limiting the ability to metabolize glucose. There is evidence that people with type 2 diabetes or insulin resistance have lower activity of oxidative enzymes and reduced aerobic capacity (24,25,40). In the present study, Vo2peak and activity of mitochondrial enzymes were positively related to SI at baseline. Despite this relationship, muscle mitochondrial variables did not contribute significantly to the multivariate model for SI after the inclusion of abdominal fat. We found that aerobic exercise training increased the glucose transport capacity (higher GLUT4) and mitochondrial content of skeletal muscle as previously reported (22,23). However, these changes were not related to the change in SI. These findings suggest that insulin action and mitochondrial biogenesis may respond to common regulatory events, such as exercise, but that the two pathways are not directly related.
We have considered other factors that may explain the age-dependent exercise response in insulin sensitivity. First, compared to the current study, training programs that improved insulin sensitivity in older people typically had more intense or frequent sessions (12,13) or were longer (6–12 months) (9,11,13). In one study, 63-year-old people engaged in low-intensity exercise (e.g., walking) showed no change in insulin action after 6 months, but improved after an additional 6 months of more intensive exercise (9). Thus, older people may require more intensive or longer exercise training programs to improve SI, whereas other factors, such as mitochondrial function, are more readily altered. A second possibility is that the effect of exercise on SI response is more rapidly lost in older people. Timing of the posttraining measurements of SI could be important. In most studies, SI was measured 14–17 h after the last exercise session (9,11,12), whereas we waited 96–120 h to examine chronic training adaptations instead of acute exercise effects. Although there was some variation in the timing of our follow-up tests (≤24 h), there was no systematic difference in the time interval across age or sex, nor was there an effect on the magnitude in SI improvement. In well-trained athletes, SI declines within 6–14 days if regular exercise is not maintained (14,41,42). Future work will need to examine how SI changes in the first 7 days after completing a training program with comparisons made between younger and older people. A third explanation is that inherent aging processes may blunt the adaptability of SI even if regular vigorous exercise is performed. It was recently shown that SI is lower in both older sedentary and endurance-trained people versus younger people with similar respective exercise status (43). Further, as we and others have found (7,8,44), the age effect on SI disappeared in sedentary subjects after controlling for body fatness (43). In contrast, after controlling for body fat, SI was still 33% lower in older athletes (43). Insulin sensitivity in the older runners was equal to or greater than that in sedentary groups, indicating a clear benefit of maintaining a long-term vigorous exercise training program (43). Nevertheless, the lower SI in older versus younger runners suggests that the capacity to improve insulin action with exercise may be somehow limited in older people.
Exercise training resulted in an average reduction in body weight of 0.6 kg, which appears to have come mainly from abdominal fat stores. This reduction was similar in visceral and subcutaneous abdominal fat depots and did not vary with age. Thus, despite the close correlation between abdominal fat and SI at baseline, the magnitude of the improvement in SI after exercise training was not related to the amount of fat lost. In overweight men, exercise training and weight loss are attributed with distinct effects on glucose metabolism that are additive when combined (45). We encouraged participants to maintain their diet and body weight in this study, so it is possible that a weight-loss component would have resulted in greater gains in insulin sensitivity in the exercise group (45,46).
Fasting insulin and glucose showed little or no change with exercise training and were therefore unrelated to changes in SI. Exercise-induced improvements in SI in the absence of a change in fasting insulin or glucose have been noted before (12,47). When reductions in fasting insulin occur in response to exercise training, a common cofactor is weight loss, specifically fat loss (9,11,13,45). Fasting insulin levels are positively associated with body fat (r = 0.65 in the present study at baseline). The exercise group had a 5% reduction in abdominal fat, but a larger decrease may be required to substantially affect fasting insulin levels.
At baseline we found that SI decreased with age, consistent with other reports (5–8). This decline appears to result from an increase in abdominal fat rather than age per se. Earlier reports found a relationship between SI and anthropometric measures like waist circumference or BMI (7,8,44). In the current study, SI was more closely related to visceral than subcutaneous fat, but SI was most closely related to total abdominal fat area, in agreement with the findings of Goodpaster et al. (48). A consensus has not been reached on whether visceral or subcutaneous fat regions are more important for conferring insulin resistance (48–50).
The decline with age in activity of mitochondrial enzymes indicates that muscle oxidative capacity is reduced (32,34,39). Previous work suggested that mitochondrial functional decline might be related to lower synthesis rate of mitochondrial proteins (32). The current results now indicate that protein synthesis in older muscle may be limited by template availability, since mRNA levels for both nuclear-encoded (COX4) and mitochondrial-encoded (ND4) respiratory chain proteins decreased with age. We tested whether these changes were related to parallel reductions in transcription factors that regulate mitochondrial genes upstream. PGC-1α has generated interest because it acts with transcription factors like NRF-1 to control expression of genes of oxidative metabolism, including TFAM (51,52). TFAM is the signal through which the nucleus regulates mitochondrial DNA transcription and replication (53). The mRNA level of PGC-1α was positively associated at baseline with that of GLUT4, NRF-1, and TFAM, supporting the evidence that PGC-1α is a key regulator of energy-utilizing pathways. However, PGC-1α, NRF-1, and TFAM transcript abundance did not change with age. This implies that the reduction in COX4 and ND4 mRNA with age must be regulated at other control points such as mRNA stability or transcription factor activity, or perhaps by other transcription factors. Oxidative damage to DNA has been shown to increase with age (54) and could limit the expression of specific mitochondrial genes in the presence of normal levels of transcription factors. We are aware of only one other study that has examined age effects on mitochondrial-related transcription factors in human muscle (55). In contrast to our findings, mRNA levels of TFAM and NRF-1 were reported to be higher in a group of elderly (71–88 years) than in younger (21–33 years) people (55). However, the muscle samples in that study were obtained from only four to seven people per group who were undergoing orthopedic surgery. The clinical state, anesthesia, or any treatments could modulate the mRNA level of these transcription factors, and the data may not be applicable to healthy populations.
The exercise training program resulted in an enhancement of mitochondrial biogenesis, as shown by several markers. There were no interactions between age and the training response of the mitochondrial measurements. Improvements in Vo2peak and oxidative enzymes in response to aerobic exercise have been previously shown in older people (56,57). Earlier studies also showed that vigorous training results in higher muscle mRNA content of TFAM and other mitochondrial genes in young men (58,59). The present study is the first to show that aerobic training stimulates expression of mitochondrial genes and transcription factors in muscle from older and younger people. The potency of the training effect on muscle oxidative pathways is shown by the fact that all of the changes in muscle that were measured were clearly evident 5–6 days after the last training session. Collectively, these findings demonstrate that despite age-related functional decline, skeletal muscle capacity for mitochondrial biogenesis remains high in older muscle when faced with the metabolic demands of regular exercise. Exercise-induced increases in muscle oxidative enzymes are consistent with higher ATP production capacity (56) and may lead to greater ability to utilize glucose. However, the present data demonstrate that changes in muscle mitochondrial function and insulin-mediated glucose disposal are not closely related.
In conclusion, 4 months of moderate-intensity aerobic exercise performed by previously sedentary men and women improved insulin sensitivity in young people but not in middle-aged and older groups. This unique finding could not be explained by loss of body fat or increased expression of glucose transporter protein in skeletal muscle, since exercise training had an equivalent effect on these parameters in people of all ages. Muscle mitochondrial enzyme activity declined with age and improved with exercise training regardless of age. The exercise-induced increase in muscle oxidative capacity was closely related to the availability of the mRNA abundance of mitochondrial proteins. These findings suggest that the ability of aerobic exercise to enhance muscle mitochondrial function is not age-limited, whereas improvement in insulin sensitivity is impaired in older people. This observation will need to be considered in the design of exercise programs aimed at preventing or delaying diabetes in older people.
Relationship between SI and age, adiposity, and insulin levels. The variance in SI and insulin was not evenly distributed, so data are shown after log transformation. SI declined with age (A) but was more closely related to total abdominal fat (B), visceral fat (C), and fasting insulin (D) levels. Regression lines are shown for pooled data from men (○) and women (•), except in C, where the solid line is for women and the dotted line is for men. P < 0.01 for all correlation coefficients shown.
Relationship between age and the post-exercise change in SI. The absolute increment in SI in exercisers was inversely related to age (top panel, regression line for entire group). The relationship was significant (P < 0.01) for both women (r = 0.53) and men (r = 0.34) when considered separately. The percent change in SI (lower panel, regression line for entire group) was also inversely related to age, but when considered separately, the effect was significant in women (r = 0.61, P < 0.01) but not in men (r = 0.16, P > 0.05). SI units in the top panel are ×10−5 · min−1 · pmol−1 · l−1.
Effect of age on abundance of mRNA for selected genes in skeletal muscle. Measurements were performed on 78 people during the baseline phase of the study. Regression lines are given for COX4 and ND4, which declined significantly with age. The other genes shown did not change with age. Values are given in arbitrary units (AU) after normalization to 28S rRNA.
Effect of the aerobic training program on mRNA abundance of selected genes in skeletal muscle. Exercise caused an increase in the level of each of these mRNAs (averages given in Table 4). This figure demonstrates that the responses to training did not differ with age or sex. Values are given as the absolute difference between the pre- and posttraining measurements, in arbitrary units (AU) after normalization to 28S rRNA.
Characteristics of the participants at baseline
Variable .
Sex .
Age-group (years)
≥70 .
n W 7 9 8 6 6 13
M 8 7 6 5 7 8
Weight (kg) W 72.2 ± 2.2 66.0 ± 2.4 68.3 ± 2.5 70.1 ± 4.0 73.6 ± 2.0 67.7 ± 2.7
M 83.2 ± 3.5 88.7 ± 4.1 90.4 ± 3.8 90.4 ± 4.7 92.5 ± 1.9 80.4 ± 4.2
BMI (kg/m2) W 24.7 ± 0.7 23.9 ± 0.8 24.8 ± 0.5 25.6 ± 1.2 27.5 ± 0.6 25.7 ± 0.8
FFM (kg) W 43.4 ± 1.1 39.8 ± 0.9 39.1 ± 0.9 39.6 ± 1.6 40.1 ± 1.5 38.0 ± 1.1
Body fat (%) W 34.1 ± 2.2 34.1 ± 1.3 37.2 ± 1.3 37.1 ± 2.0 40.3 ± 1.4 38.9 ± 1.5
Abdominal fat (cm2) W 201 ± 49 141 ± 16 244 ± 42 206 ± 43 288 ± 53 278 ± 32
M 230 ± 69 325 ± 32 355 ± 56 352 ± 41 443 ± 34 363 ± 45
Visceral fat (cm2) W 45 ± 19 30 ± 4 69 ± 18 51 ± 15 107 ± 26 99 ± 15
Data are means ± SE. Significant differences between men and women were present for all variables. With increasing age, there was a significant decline in FFM and significant increases in percent body fat, total abdominal fat, and visceral fat (P < 0.01). Correlation coefficients between these variables and age are shown in Table 2.
Univariate correlations between age, insulin sensitivity index, and selected variables
Women .
Men .
Abdominal fat, total (cm2) 0.41* 0.38* −0.62* −0.67*
Abdominal fat, visceral (cm2) 0.51* 0.41* −0.61* −0.58*
Abdominal fat, subcutaneous (cm2) 0.28 0.22 −0.56* −0.57*
Waist circumference (cm) 0.42* 0.39* −0.59* −0.43*
Total body fat (%) 0.44* 0.32* −0.43* −0.28
Total body FFM (kg) −0.32* −0.35* −0.16 −0.21
BMI (kg/m2) 0.35* 0.25 −0.43* −0.55*
Total cholesterol (mmol/l) 0.57* 0.36* −0.26 −0.36*
Triglycerides (mg/dl) 0.47* 0.27 −0.36* −0.59*
Insulin (pmol/l) 0.37* 0.02 −0.55* −0.60*
Glucose (mmol/l) 0.49* 0.42* −0.25 −0.40*
Nonesterified fatty acids (μmol/l) 0.28 0.38* 0.03 −0.30
Vo2peak (ml · kg−1 FFM · min−1) −0.84* −0.82* 0.44* 0.31*
Citrate synthase (units/min) −0.37* 0.03 0.36* 0.51*
Cytochrome c oxidase (units/min) −0.46* −0.36* 0.31 0.37*
COX4 mRNA (arbitrary units) −0.32* −0.45* −0.03 0.23
ND4 mRNA (arbitrary units) −0.45* −0.50* 0.18 0.20
GLUT4 mRNA (arbitrary units) 0.29 0.04 0.07 0.29
P < 0.025.
Aerobic capacity, body composition, blood variables, and insulin sensitivity before and after control or exercise training periods
Before .
After .
Vo2peak (ml · kg−1 FFM · min−1) 40.7 ± 1.4 40.3 ± 1.2 40.5 ± 1.1 44.3 ± 1.2*
Weight (kg) 77.8 ± 2.0 78.1 ± 2.0 79.2 ± 1.6 78.7 ± 1.6*
Waist circumference (cm) 89.7 ± 1.7 91.9 ± 1.5* 91.9 ± 1.4 90.0 ± 1.5*
BMI (kg/m2) 25.7 ± 0.3 25.9 ± 0.4 26.6 ± 0.3 26.4 ± 0.3*
FFM (kg) 49.1 ± 1.8 49.3 ± 1.8 50.1 ± 1.4 50.1 ± 1.4
Body fat (%) 31.2 ± 1.3 31.0 ± 1.3 31.4 ± 0.9 31.0 ± 0.9
Abdominal fat, total (cm2) 299 ± 23 299 ± 22 318 ± 17 299 ± 18*
Abdominal fat, visceral (cm2) 122 ± 13 121 ± 12 133 ± 11 124 ± 11*
Abdominal fat, subcutaneous (cm2) 177 ± 13 178 ± 13 185 ± 9 174 ± 10*
Total cholesterol (mmol/l) 5.07 ± 0.17 4.85 ± 0.19 4.90 ± 0.16 4.66 ± 0.12
HDL cholesterol (mmol/l) 1.25 ± 0.12 1.15 ± 0.08 1.17 ± 0.06 1.33 ± 0.11
LDL cholesterol (mmol/l) 3.03 ± 0.15 2.99 ± 0.18 3.00 ± 0.15 2.76 ± 0.13
Triglycerides (mg/dl) 153 ± 13 137 ± 14* 146 ± 11 114 ± 7*
Fasting insulin (pmol/l) 35 ± 3 37 ± 3 38 ± 3 34 ± 2
Fasting glucose (mmol/l) 5.4 ± 0.1 5.3 ± 0.1 5.3 ± 0.1 5.3 ± 0.1
Nonesterified fatty acids (μmol/l) 520 ± 22 512 ± 18 524 ± 15 494 ± 14*
Insulin sensitivity index (× 10−5 · min−1 · pmol−1 · l−1) 5.50 ± 0.53 5.22 ± 0.58 4.88 ± 0.36 6.27 ± 0.60*
Data are means ± SE.
Before-to-after difference within group, P < 0.025. None of the before-to-after changes differed with age or sex, except insulin sensitivity.
Values for muscle variables before and after control or exercise training periods
Citrate synthase activity 24.0 ± 1.2 25.1 ± 1.2 24.1 ± 0.8 35.1 ± 1.3*
Cytochrome c oxidase activity 6.3 ± 0.6 7.3 ± 0.8 7.1 ± 0.5 13.3 ± 0.7*
COX4 mRNA 1.00 ± 0.08 1.02 ± 0.09 0.92 ± 0.06 1.54 ± 0.13*
ND4 mRNA 0.76 ± 0.06 0.77 ± 0.06 0.73 ± 0.04 1.19 ± 0.09*
PCG-1 mRNA 1.66 ± 0.15 1.49 ± 0.13 1.48 ± 0.10 2.29 ± 0.15*
NRF-1 mRNA 0.83 ± 0.10 0.80 ± 0.10 0.71 ± 0.06 0.82 ± 0.07*
TFAM mRNA 0.91 ± 0.15 0.99 ± 0.14 0.81 ± 0.07 1.50 ± 0.13*
GLUT4 mRNA 0.87 ± 0.07 0.92 ± 0.08 0.82 ± 0.06 1.25 ± 0.07*
Data are means ± SE. Enzyme activities are given as μmol·min−1·g−1 tissue; mRNA levels, as arbitrary units after normalization to 28S rRNA.
Before-to-after difference within group, P < 0.001 for all variables except NRF-1, which was P < 0.02. None of the changes in the exercise group had a significant interaction with age or sex.
Funding was provided by Public Health Service Award RO1AG09531, Mayo Foundation, and the Dole-Murdock Professorship (K.S.N.), National Research Service Award T32-DK07352 and the Mayo-Thompson Fellowship (K.R.S.), and GCRC Grant MO1-RR00585.
The authors are grateful for the valuable technical support provided by Jane Kahl; Dawn Morse; Rebecca Kurup; Karen Townsend; the GCRC nurses, dieticians, and support staff; and the staff of the Healthy Living Center. We also thank the volunteers who completed the protocol.
Mokdad AH, Ford ES, Bowman BA, Dietz WH, Vinicor F, Bales VS, Marks JS: Prevalence of obesity, diabetes, and obesity-related health risk factors, 2001.
Ford ES, Giles WH, Dietz WH: Prevalence of the metabolic syndrome among US adults: findings from the Third National Health and Nutrition Examination Survey.
Crespo CJ, Keteylan SJ, Heath GW, Sempos CT: Leisure-time physical activity among US adults.
Arch Intern Med
Mokdad AH, Bowman BA, Ford ES, Vinicor F, Marks JS, Koplan JP: The continuing epidemics of obesity and diabetes in the United States.
Shimokata H, Muller DC, Fleg JL, Sorkin J, Ziemba AW, Andres R: Age as independent determinant of glucose tolerance.
Houmard JA, Weidner MD, Dolan PL, Leggett-Frazier N, Gavigan KE, Hickey MS, Tyndall GL, Zheng D, Alshami A, Dohm GL: Skeletal muscle GLUT4 protein concentration and aging in humans.
Khort WM, Kirwin JP, Staten MA, Bourey RE, King DS, Holloszy JO: Insulin resistance in aging is related to abdominal obesity.
Coon PJ, Rogus EM, Drinkwater D, Muller DC, Goldberg AP: Role of body fat distribution in the decline in insulin sensitivity and glucose tolerance with age.
Seals DR, Hagberg JM, Hurley BF, Ehsani AA, Holloszy JO: Effects of endurance training on glucose tolerance and plasma lipid levels in older men and women.
Hughes VA, Fiatrone MA, Fielding RA, Kahn BB, Ferrara CM, Shepherd P, Fisher EC, Wolfe RR, Elahi D, Evans WJ: Exercise increases muscle GLUT-4 levels and insulin action in subjects with impaired glucose tolerance.
–E862,
Kirwin JP, Khort WM, Wojta DM, Bourey RE, Holloszy JO: Endurance exercise training reduces glucose-stimulated insulin levels in 60- to 70-year old men and women.
J Gerontol
Cox JH, Cortright RN, Dohm GL, Houmard JA: Effect of aging on response to exercise training in humans: skeletal muscle GLUT-4 and insulin sensitivity.
J Appl Physiol
Kahn SE, Larson VG, Beard JC, Cain KC, Fellingham GW, Schwartz RS, Veith RC, Stratton JR, Cerqueira MD, Abrass IB: Effect of exercise on insulin action, glucose tolerance, and insulin secretion in aging.
Houmard JA, Tyndall GL, Midyette JB, Hickey MS, Dolan PL, Gavigan KE, Weidner MD, Dohm GL: Effect of reduced training and training cessation on insulin action and muscle GLUT4.
Tuomilehto J, Lindstrom J, Eriksson JG, Valle TT, Hamalainen H, Ilanne-Parikka P, Keinanen-Kiukaanniemi S, Laakso M, Louheranta A, Rastas M, Salminen V, Uusitupa M: Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance.
Hu FB, Manson JE, Meir JS, Colditz G, Liu S, Solomon CG, Willet WC: Diet, lifestyle, and the risk of type 2 diabetes mellitus in women.
Eriksson KF, Lindgarde F: Prevention of type 2 (non-insulin-dependent) diabetes mellitus by diet and physical exercise: the 6-year Malmo feasibility study.
Diabetes Prevention Program Research Group: Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin.
American College of Sports Medicine: The recommended quantity and quality of exercise for developing and maintaining cardiorespiratory and muscular fitness, and flexibility in healthy adults.
Med Sci Sports Exer
Zierath JR, He L, Guma A, Wahlstrom E, Klip A, Wallberg-Henriksson H: Insulin action on glucose transport and plasma membrane GLUT4 content in skeletal muscle from patients with NIDDM.
Garvey WT, Maianu L, Zhu JH, Brechtel-Hook G, Wallace P, Baron AD: Evidence for defects in the trafficking and translocation of GLUT4 glucose transporters in skeletal muscle as a cause of human insulin resistance.
Ryder JW, Chibalin AV, Zierath JR: Intracellular mechanisms underlying increases in glucose uptake in response to insulin or exercise in skeletal muscle.
Holloszy JO, Coyle EF: Adaptations of skeletal muscle to endurance exercise and their metabolic consequences.
Simoneau JA, Veerkamp JH, Turcotte LP, Kelley DE: Markers of capacity to utilize fatty acids in human skeletal muscle: relation to insulin resistance and obesity and effects of weight loss.
Simoneau JA, Kelley DE: Altered glycolytic and oxidative capacities of skeletal muscle contribute to insulin resistance in NIDDM.
Boirie Y, Short KR, Ahlman B, Charlton M, Nair KS: Tissue-specific regulation of mitochondrial and sarcoplasmic protein synthesis rates by insulin.
Huang X, Eriksson KF, Vaag A, Lehtovirta M, Hansson M, Laurila E, Kanninen T, Olesen BT, Kurucz I, Koranyi L, Groop L: Insulin-regulated mitochondrial gene expression is associated with glucose flux in human skeletal muscle.
Pendergrass M, Koval J, Vogt C, Yki-Jarvinen H, Iozzo P, Pipek R, Ardehali H, Printz R, Granner D, DeFronzo RA, Mandarino LJ: Insulin-induced hexokinase II expression is reduced in obesity and NIDDM.
Ojuka EO, Jones TE, Nolte LA, Chen M, Wamhoff BR, Sturek M, Holloszy JO: Regulation of GLUT4 biogenesis in muscle: evidence for involvement of AMPK and Ca2+.
–E1013,
Freyssenet D, DiCarlo M, Hood DA: Calcium-dependent regulation of cytochrome c gene expression in skeletal muscle cells: identification of a protein kinase C-dependent pathway.
Michael LF, Wu Z, Cheatham RB, Puigserver P, Adelmant G, Lehman JL, Kelly DP, Spiegelman BM: Restoration of insulin-sensitive glucose transporter (GLUT4) gene expression in muscle cells by the transcriptional coactivator PGC-1.
Rooyackers OE, Adey DB, Ades PA, Nair KS: Effect of age on in vivo rates of mitochondrial protein synthesis in human skeletal muscle.
Barazzoni R, Short KR, Nair KS: Effects of aging on mitochondrial DNA copy number and cytochrome c oxidase gene expression in rat skeletal muscle, liver, and heart.
Papa S: Mitochondrial oxidative phosphorylation changes in the life span. Molecular aspects and pathophysiological implications.
Biochim Biophys Acta
Balagopal P, Schimke JC, Ades P, Adey D, Nair KS: Age effect on transcript levels and synthesis rate of MHC and response to resistance exercise.
Proctor DN, Beck KC: Delay time adjustments to minimize errors in breath-by-breath measurements of Vo2 during exercise.
Avagadro A, Bristow JD, Bier DM, Cobelli C, Toffolo G: Stable-label intravenous glucose tolerance test minimal model.
Jensen MD, Kanaley JA, Reed JE, Sheedy PF: Measurement of abdominal and visceral fat with computed tomography and dual-energy x-ray absorptiometry.
Am J Clin Nutr
Houmard JA, Weidner ML, Gavigan KE, Tyndall GL, Hickey MS, Alshami A: Fiber type and citrate synthase activity in the human gastrocnemius and vastus lateralis with aging.
Regensteiner JG, Bauer TA, Reusch JEB, Brandenburg SL, Sippel JM, Vogelsong AM, Smith S, Wolfel EE, Eckel RH, Hiatt WR: Abnormal oxygen uptake kinetic responses in women with type II diabetes mellitus.
Rogers MA, King DS, Hagberg JM, Ehsani AA, Holloszy JO: Effect of 10 days of physical inactivity on glucose tolerance in master athletes.
Vukovich MD, Arciero PJ, Kohrt WM, Racette SB, Hansen PA, Holloszy JO: Changes in insulin action and GLUT-4 with 6 days of inactivity in endurance runners.
Clevenger CM, Jones PP, Tanaka H, Seals DR, DeSouza CA: Decline in insulin action with age in endurance-trained humans.
Weidner MD, Gavigan KE, Tyndall GL, Hickey MS, McCammon MR, Houmard JA: Which anthropometric indices of regional adiposity are related to the insulin resistance of aging?
Dengel DR, Pratley RE, Hagberg JM, Rogus EM, Goldberg AP: Distinct effects of aerobic exercise training and weight loss on glucose homeostasis in obese sedentary men.
Kelley DE, Goodpaster BH: Skeletal muscle triglyceride: an aspect of regional adiposity and insulin resistance.
Houmard JA, Shinebarger MH, Dolan PL, Leggett-Frazier N, Bruner RK, McCammon MR, Isreal RG, Dohm GL: Exercise training increases GLUT4 concentration in previously sedentary middle-aged men.
Goodpaster BH, Thaete FL, Simoneau JA, Kelley DE: Subcutaneous abdominal fat and thigh muscle composition predict insulin sensitivity independently of visceral fat.
Abate N, Garg A, Peshock RM, Stray-Gunderson J, Adams-Huet B, Grundy SM: Relationships of generalized and regional adiposity to insulin sensitivity in men.
Kelley DE, Thaete FL, Troost F, Huwe T, Goodpaster BH: Subdivisions of subcutaneous abdominal adipose tissue and insulin resistance.
Scarpula RC: Nuclear activators and coactivators in mammalian mitochondrial biogenesis.
Lin J, Wu H, Tarr PT, Zhang CY, Wu Z, Boss O, Michael LF, Puigserver P, Isotani E, Olson EN, Lowell BB, Bassel-Duby R, Spiegelman BM: Transcriptional co-activator PGC-1α drives the formation of slow-twitch muscle fibers.
Gordon JW, Rungi AA, Inagaki H, Hood DA: Effects of contractile activity on mitochondrial transcription factor A expression in skeletal muscle.
Hamilton ML, Van Remmen H, Drake JA, Yang H, Guo ZM, Kewitt K, Walter CA, Richardson A: Does oxidative damage to DNA increase with age?
Lezza AMS, Pesce V, Cormio A, Fracasso F, Vecchiet J, Felzani G, Cantatore P, Gadaleta MN: Increased expression of mitochondrial transcription factor A and nuclear respiratory factor-1 in skeletal muscle from aged human subjects.
FEBS Lett
Berthon P, Freyssenet D, Chatard JC, Castells J, Mujika I, Geyssant A, Guezennec CY, Denis C: Mitochondrial ATP production rate in 55 to 73-year-old men: effect of endurance training.
Coggan AR, Spina RJ, King DS, Rogers MA, Brown M, Nemeth PM, Holloszy JO: Skeletal muscle adaptations to endurance training in 60- to 70-yr-old men and women.
Bengtssson J, Gustofsson T, Widegren U, Jansson E, Sundberg CJ: Mitochondrial transcription factor A and respiratory complex IV increase in response to exercise training in humans.
Pflugers Arch
Puntschart A, Claassen H, Jostarndt K, Hoppeler H, Billeter R: mRNAs of enzymes involved in energy metabolism and mtDNA are increased in endurance-trained athletes.


Over the course of the 48 hour weekend, this NAS sent out over three and a half thousand emails! 3500+ emails! All to our logging email addresses, which then sent it out to the members of the team. 5 team members, 3500+ emails.... 17,500 emails being sent and received. That's a lot email in a short time. Most email servers will handle that and ours certainly did. Fortunately too we use G-Suite (Google Apps new fancy name) and so the volume of mail wasn't an issue.
What became an issue though - and this did have an effect on our phones and mobile devices picking up email - was that another network device - a disaster recovery server - also suffered heat stress from failed air conditioning. A sparky had unplugged our monitoring device to charge his tools and hadn't plugged it back in, so we had no idea what was happening (this was Sunday afternoon). When the A/C failed, the server turned off and the replication servers started to complain - four of them, every 30 seconds.... Over 12 hours those servers alerted our logging email address over 5,000 coming in and going back out - another 25,000 emails hitting phones plus the other emails as well.
Having had the discussion with clients about hosted email solutions versus onsite solutions, there are definite advantages to having huge servers managing your email. So if you don't have a cloud based solution, how can you mitigate this risk?
Defence in depth is a great place to start. Organise to get a mail exchanger - MXGuardDog or something similar. Westnet used to do one too. Get your MX records updated to punch mail through that. These then relay to av-relay.domainname.com. Configure your firewall to only accept emails from the IPs at MXGuardDog (for example) and drop everything else (or at least grey list it so it gets dropped and the sending server can try other MX records).
This way you can temporarily control the flow without having your ADSL or NBN connection getting flogged to death.
Configure your internal mailer to hold emails for this kind of thing - to recognise a flood of email and trickle it out where possible. The risk is that legitimate email (which these emails both are and aren't) will get lost in the flow. It's better than having your upload link fully saturated though (which will kill all internet connectivity).
DoS are bad. DDoS are worse. Let's try to avoid doing it to ourselves!
In the course of work and university I've been jumping a bit between Word, Pages and Docs for various reasons. I thought it might be useful to compare them. Let's start.
On price Docs is the obvious winner. Free to get access to and solid support on mobile devices.
Simple and uncluttered with everything there and looking like every single other word processor through history.
Pages has a different take on it, and one that can be a bit confusing to begin with.
The sidebar gets added into the mix, and many controls are moved out of the top menu and into here. I don't mind this personally, but I do find on the MacBook that I dislike losing the screen real estate to this menu. It is functional though.
Since Microsoft changed the menu titles back to being in regular capitals / lower case, the readability of these menus has improved immensely. I remember when the ribbon came out and people loathed it. It just is now and I find it to be quite useful. The drawback for me with Microsoft Word is the sheer number of options available. We are spoiled for choice, control and capabilities and it can be overwhelming at times.
The usability winner is a totally individual choice and I leave it up to you to decide. Personally I like Pages but I'm ok getting around all three.
This is a big one to consider. Word has clearly got it all (and most users will touch about 10% of it's capabilities day to day). Pages is likewise heavy on features and Docs comes in last, with its smaller range of functions. I think because Docs is web based then it was forced into more simplistic functionality and Google had to really choose the key word processing capabilities to include.
There is one function that stands Word out from Pages though in these heavy hitters. The ability to have a section in landscape, while the rest of the document is in portrait is not available in Pages (that I could find). Now most people probably won't care about this overly, but for me, if I'm inserting a large landscape graphic or big table it is critical and stupid Pages won't do it. Very frustrating. I've never really tried it in Docs, but a 3 second Google search shows it's not possible. Word wins for this!
All three offerings have Table of Content, header, footer, page numbers, insert stuff blah blah - you get the drift. All the basics and day-to-day stuff is there, and its only the more advanced activities where they are differentiated.
Which one is the prettiest? A very subjective question of course. It should be noted that Apple have spent a lot of time on fonts and appearance, but so have Google and Microsoft (they just aren't as talked about). This is up to you - but I rank them Pages, Docs, and Word. Word is a bit busy for me - lots going on and when I'm working on an assignment or report I need clarity. Docs is very good for this, but something about the Pages appearance appeals to me.
Pages is Apple centric - don't bother looking for it on anything that doesn't have the Apple logo. That being said, it integrates very well with iCloud and syncs to your mobile device quite happily.
Word is starting to become ubiquitous everywhere - Microsoft have released Office365 in a web browser, it's installable and available as an app on most mobile devices. The experience is the same across them all and really is improving.
Google Docs is maturing constantly and more features are being added frequently. For collaboration it is King. See updates and writing by other people in almost real time and easily give various levels of access to documents. For working with colleagues Docs is the best - Pages and Word are not in the same realm.
While I have been a fan of OTRS for many years and like the interface, reporting and usability of it, I recently chanced across osTicket (from the TV series Mr Robot). It looked interesting and a client I have wants an internal ticket management system (they had also seen it). After a bit of to and fro, they agreed to some research time and I set up osTicket.
Have a look at that if you want to install it - it's pretty straightforward.
osTicket Task view - got some work to do on NFS No Limits!
You can see in the Tickets there is an NFS No Limits ticket. Under the tasks panel, you can see I've broken this down further into the things I need to do with that Ticket. I imagine with multiple agents, the tasks could be spread around.
So why not migrate to osTicket? The ability to capture time in osTicket seems to be hideously complicated to implement. Perhaps I need to do more research into that, but in OTRS its pretty straightforward. For a company just interested in getting things done, then the time capture isn't so important, but for us - its a big part of the job being completed. Reporting is still something I need to investigate. The reporting in OTRS is great (once you get your head around it) so I'll be interested to play with osTicket a bit more and see how it goes. Stay tuned for more updates...!
2017 - a new year and new challenges in IT ahead!
We're at the 10th day of January and I've already had servers lose their Kerberos connectivity with active directory, our first cryptolocker infection and so much more.... I need a lot more coffee to deal with this pish.
Stay tuned - I'm hoping to get my hands on some new tech and describe, some old tech and revive it, and just generally putter around for your amusement.
MacBook Pro's (2012) can and do lose their wifi capability - I think the on-board adapter and finding one that works with a Mac can be tricky.
Plus all the stuff on fixing Kerberos etc which will be the subject of a post down the track.


Here I am, looking at a screen, showing a small video...of a fake screen, showing a small video.
Evelien Lohbeck has created this paper wireless notebook animation illusion.
"Noteboek (English title: Notebook) consists of 4 short experimental films where I try to confuse the reality. In these films, illusions and expectations are challenged."
Perhaps it goes without saying, but as any website designer well tell you, the best way to design a website, is on a sheet of paper.
But hey, no respectable user using a paper netbook would use internet explorer ?


text:
BOYS SOCCER: Huron knocks off Pirates
By Mike Dezotell |
PUBLISHED: October 7, 2009 at 10:13 a.m. | UPDATED: July 15, 2021 at 11:23 a.m.
PERKINS TWP — Huron junior forward Nico Samaniego has had some pretty good games during his career has a Tiger. Even though Samaniego still has nearly a season and a half to wear a Huron uniform, he may have had his most memorable game of his career on Tuesday night, scoring three goals to lift Huron past Perkins, 3-2, in a Sandusky Bay Conference showdown. "I'm so happy right now," said an elated Samaniego, whose Tiger squad avenged an early season 3-1 loss to the Pirates. "This is the greatest game I have ever played, and for it to be against Perkins it makes it that much more special." With the teams knotted up at 2-2, Samaniego found himself with the ball about 20 feet from the goal. He used a side step move to clear himself of the Perkins defender and found the back of the net with just 46 seconds remaining in the contest. Ironically, the goal that Samaniego scored was against his cousin Danik Kumar, the back-up goal keeper for Perkins. Kumar had to come in the game when starting goal keeper, Alex Trautman, left the game with a concussion. Early in the match he took a hard fall and hit his head. "That was tough for him to come in the last two minutes of the game without playing the whole game," Samaniego said. "Coaches always stress how important it is to make sure you warm up before going in, so I was at a bit of a disadvantage because of that." With the rain falling hard during the first half of play, it looked as if the teams would go into halftime with a 0-0 tie. Samaniego had other ideas when he received a strong pass from John Duzsa and took the ball near the goal with under five seconds to play. He waited until the last possible second and scored as time expired to give Huron a 1-0 halftime lead. "That was just Nico making a great play and using great time management." Said Huron coach Matt Asher, whose squad improved to 8-3-1. Perkins wasted no time regaining control, however, when the second half started — scoring two goals in two minutes. Nathan Huntley tied the game at 1-1 with 38:50 left in the second half on a breakaway. Just 1:30 later senior Chris Baxter was awarded a penalty kick and cashed it in to give Perkins a 2-1 lead. "This was a tough loss," said Pirates coach Juan Romero, whose squad fell to 8-3-1. "There is not a lot to say, I thought both teams had their opportunities and Huron was able to pull it out." "We got them at their field, and they got us at ours." Romero said. "These were two teams battling and they both put forward a great effort. Perkins goal keeper Alex Trautman finished with 8 saves. Tigers netminder Chase Greenawalt finished with 9 saves.
Mike Dezotell

redpajama_set_name: RedPajamaCommonCrawl


Welcome to a scrappy, independently owned shop that works for our clients, not some far-removed shareholders. Welcome to a group of people dedicated to making our brands the best in their industry. We have a full spectrum of interactive services from design to programming.


Enhance your Titanfall™ experience with the Titanfall™ Companion App. Provides you with notifications for all of the latest info and updates to Titanfall™. Features rich intel about the history of the Titanfall™ universe, characters, weapons, maps, modes and controls. Now review your stats from anywhere including total kills, favorite weapons, time spent playing and more. Includes exciting features available when connected with your Xbox One Console. With the second-screen map feature, you have at your fingertips a full screen, real-time interactive mini-map of the game you're playing. See and track your teammates and where the action is happening live and with the ability to zoom in and out to focus on key areas of the map. With Titanfall™ Companion App, you will have the ultimate Titanfall™ experience.
Titanfall™ ©2014 Respawn Entertainment, LLC. Titanfall is a trademark of Respawn Entertainment, LLC. EA and the EA logo are trademarks of Electronic Arts Inc.
When it works, it's pretty cool. A full screen map and it lets you look at stats from previous games and challenges. However, since a couple of recent updates, the app has done nothing but crash the game. Don't download until it gets fixed.
App is and has been working fine for me for quite some time. Nothing for Frontier Defense, but other than that, it's fine.
Review title of AntonioWonderful App! 100% recomendé!
Very good App. Finally we are getting some Windows 8 companion apps!
Review title of TimCrashes Titanfall once connected.
Every time I enter Titanfall without the app it works. But when I try to use this separate app (which I also Dont understand. Why didn't you use Xbox Smartglass instead of another making another app to download. Its not like you're getting to a wider audience.) But when I have both Titanfall and this app open Titanfall just doesn't work.
Pros: provides real time map movements of you and teammates, real time stats, works well Con: Should have a way to setup classes. Great app overall.
Love having the full map up while playing the game on Xbox One..
Crashes Titanfall on Xbox One as soon as it connects.


Yesterday, I promised you a sample script of one of our new market update videos. Well, we'll do you one better. Here's a raw, uncut trial video – today's mid-day Stock Market Power Lunch segment.
Understand that in the future these will have better lighting, higher quality footage, real intros and real outros. But for now, we're just working on refining content and whatnot. So here you go.
Not a real artist. Image not drawn to scale. Don't try this at home.


Dustin Penner's first game as a King was definitely different from their collapse against the Red Wings in the 7-4 loss Monday. The Kings went from a game where 11 goals were scored to a game where the only goal was the game winning power play goal by Jarret Stoll at 12:13 in the 3rd period. When talking about the upcoming playoffs, Stoll mentioned that "You really can't have a bad period any more." With any luck, the game against the Red Wings Monday combined with the addition of Dustin Penner will be what the Kings need to shake them up and get them into playoff mode as the regular season winds down.
Bernier got his second shutout of the season tonight in LA, but Terry Murray said he hasn't thought about who will start on Saturday yet when asked if Bernier's performance tonight has him thinking of starting him on Saturday. Jonathan Quick was definitely less than stellar Monday night against the Red Wings, but one can hardly blame him completely for the Kings' breakdown that night. The Kings did well in their last afternoon game, but I'm sure Kings fans are crossing their fingers that their team can play two afternoon games in a row at a high level and stay in the playoff mix.
The Western Conference is so tight that one win moved the Kings from 8th to 5th place (and the Coyotes, who have played two more games than the Kings, but are tied in points with 76) down to 6th from 5th. Terry Murray often talks about how important the four point games are within the division and at this time of the season, these games seem even more important in a tight conference.


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Kennedy was charged with one misdemeanor charge of driving while impaired by drugs on July 13, 2012. She said she had accidentally taken an Ambien instead of a thyroid medication. Her attorneys argued she would not have been charged if she had not been part of the Kennedy family. The jury deliberated for just an hour before finding her not guilty.
A plea deal would have hurt Kennedy's humanitarian work, she told Lauer. She is currently focused on improving the rights of migrant workers.


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Andy Murray to retire at Wimbledon, could be sooner
Andy Murray announced his impending retirement at an emotional press conference at the Australian Open. Murray said he hopes to Wimbledon to be the "end point" but said retirement could come sooner.
Murray has struggled since his hip surgery last year. Murray said,
"I'm not feeling good. I've been struggling for a long time. Been in a lot of pain for 20 months now. Pretty much done everything I could to make my hip feel better. "Wimbledon is where I would like to stop playing but I'm not certain I'll be able to do that. I'm not certain I can play through the pain for another four or five months.
Considered part of the Big Four along with Roger Federer, Rafael Nadal and Novak Djokovic, Murray achieved many firsts for Britain, including becoming the country's first number one ranked player.
Murray's career in numbers:
World Number One: Murray became the first British singles player ever to officially be ranked world number one on November 7, 2016.
41 The number of weeks Murray spent on top of the rankings.
Three grand slam titles
11 grand slam finals
45 career singles titles
Two doubles titles – both with his brother, Jamie
Two Olympic singles gold medals
11 Murray won every rubber he contested to drive Great Britain to Davis Cup glory in 2015
663 Tour-level matches won
$61 million total career prize money
29 combined wins against Federer, Nadal and Djokovic
Hip surgeries are never easy to recovery from and play tennis at the highest level. But to see Murray go out limping is a bit sad. He had a great career by any measure and will be remembered fondly by fellow players and fans. He will especially remembered fondly in Britain for a long time.
Well done, mate!
Reilly Opelka Trolls US Open Organizers By Bringing Back His "Unapproved Bag"
Daniil Medvedev Is The Tallest World Number 1 In Tennis History
Caroline Wozniacki To Join Tennis Channel For Indian Wells And Miami


Payday Loans in Elk Grove, CA - 24/7 Online! Bad credit OK & No fax.
You fill out only one application and hundreds of credit companies get it immediately! Due to the high competition among lending institutions You can get low interest rate on payday loan in Elk Grove (CA)!
Direct Lender: "California Check Cashing Stores"
I take the money in the "CCCS" all the time. Yes, it's a bit expensive but it is very handy when there is nowhere to take the money. Each subsequent loan get even easier than the previous one (you get identified account).
The people are friendly and always smiling. Even in stressful situations, they do not lose their self-control and do not raise their voices to you.
This is incompetent and cunning people. They told me interest rates by phone, but in fact (when I came to them) proved that they are above! They rely on the fact that people do not go looking for another organization and get a loan from them (at exorbitant rates).
The pet and pet related industry is an astonishing $47 billion industry, and with it comes great opportunities to start a business in it. With many people in America and around the world start adopting pets, and at the same time getting busier since the global recession, the pet care business is an attractive opportunity to get a slice of the multi-billion Dollar market.
To get started, no special education are needed. However, you'll still need the genuine care for and experience with animals. For an added value, you can combine the business with pet training and pet grooming service. Later on, you can also expand to be a pet and pet supplies store, becoming an all-in-one pet service business.
Can't wait to start a pet care business ASAP?
Then these few considerations should help get you started.
You can start with below $10,000, provided you want to start from home. Getting your own place will increase your credibility and marketability, however, lease cost can get costly. Most of your expenses will go to equipment (pet toilet, food bowls, etc) and pet food and supplies stocks. If you want to also start a grooming and training business, then you will also need the necessary equipment. However, in general this business have a relatively low startup investment.
Most states will require a special permit for animal-related business. As you will also handle other people's pets, getting a third-party liability insurance that covers animal accidents and injuries is almost a necessity. Animal behavior can get unpredictable sometimes, so better safe than sorry later.
Consult your local authorities for information regarding licenses and permits. If there's any pet care association near your location, they might also help with information and application process.
Join local pet communities to introduce your business. Prepare brochures and business cards. You can also start a website with supporting social media campaigns to create an online presence. A park might be a good place where local pet owners gather and walk their pets, a perfect place to spread your flyers and brochures.
Depending on the range of service you offers, the price you should offer can also vary accordingly. Research the current market condition and competition to get a picture of how much, and how you should charge. Would your local demographics prefer hourly pay or a daily fee? Would your clients pay more for pet delivery after a daycare? Gather enough information and tailor your pricing options accordingly.
Most pet care service offers activities to be done during day care, so it's a necessary value to offer customers. Try to be as creative as you can in creating activity programs, as it may be the main value customers seek from you. The types of food you provide and optional medical care can also be attractive for clients.
A pet day care business can earn you $22-$45 per pet. Assuming you got five pets per day as an average, your earning is already an excellent $5,000 monthly or around $60,000 annually.
As your client base grows, you can opt for an expansion to other business models as mentioned above, increasing your earning and profitability potential.


We've got the perfect Father's Day present for your Dad! He can both join for only $9.95 per week with NO CONTRACT! That means he can stay on as long as he likes, for the low price of only $9.95 a week. What a bargain!!
You can pay the $9.95 p/w for your Dad if you like, or just bring him in to sign up himself.
If you'd like to offer your Dad a membership as a gift, give us a call and we'll make you a cool voucher to give to him on Father's Day.
Please note, members of Boat House Gym must purchase security tags. Security tags cost $70, $20 of this is redeemable upon termination of your membership if the security tag is returned.
Sign up here by Sunday 2nd September!
Go to the 'sign up here' button, then give us a call on 0439 356 299 to make an appointment to get your Key Tag and a personalised program. We can't wait to meet you!
Information on how to sign up forms part of the terms of entry. Signing up is deemed acceptance of these terms and conditions.
New members must register by Sunday 2nd September 2018 via the website or in the Boat House Gym office.
All members of The Boat House Gym MUST purchase a key tag for entry. Key tags are $70. ($20 is refundable at the termination of your membership if key tag is returned to the gym).
This membership is on a no contract basis and is $9.95 per person, per week on a direct debit or credit card basis only.
Cancellation of membership requires thirty days notice. Payments will still be debited until the thirty days notice has expired.
Debit cards and credit cards are charged a fee for processing payments.
Sign up requires a membership application to be completed and includes all terms and conditions as listed on the membership form.


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Mike Burngasser, of Industry Sign & Graphics, prepares to mount a historical plaque on the outside, front wall of the Domestic Abuse Women's Network (DAWN) administrative office and community services hub at 221 W. Gowe St., last Friday. The building, originally a horse stable in the early 1900s, became a supermarket and then a bank, among other things. MARK KLAAS, Kent Reporter
History takes rightful place on the wall
Descriptive, interpretive plaques adorn vintage buildings throughout downtown Kent
by Mark Klaas
Friday, June 29, 2018 7:51am
History is written right on the outside walls of storied buildings in downtown Kent.
For all to see.
A group of volunteers from the Greater Kent Historical Society (GKHS) has brought that interpretive information to life in the form of plaques that were affixed to 13 sites throughout the downtown historic district last Friday.
The project, the brainchild of local historian, GKHS member and city Landmarks Commissioner Nancy Simpson, was two years in the making. The GKHS raised money to fund the project, with each plaque costing about $350 each. A volunteer group from the society gathered carefully researched, relevant information about each historical site for about a year.
"They look terrific. They did a good job, very thorough," said Simpson, observing the plaque describing the long history of the First National Bank Building at the southwest corner of First Avenue South and Gowe Street. "I couldn't be happier with the company that's done this."
About three years ago, Simpson approached the Kent Downtown Partnership and its executive director, Barbara Smith, about the idea of producing the historic plaques to various buildings. Smith, in turn, helped find a vendor that could create the plaques.
"There were a number of other hoops Nancy had to jump through, but true to her reputation, she stayed the course, and the program came to fruition today," Smith said. "The KDP is so proud to be associated with this project and feels it adds a tremendous value to our downtown.
"We are proud of our history, and we love sharing it," Smith added. "Working with other people, organizations, the city, it all makes for a positive way to get things done."
Mike Burngasser, who works for Industry Sign & Graphics, the makers of the 1-foot-square plaques, was busy putting up the weather-coated, brush-aluminum signs at selected historic buildings last Friday.
The plaques bear a historical photo of the building, along with its own story – its origins, caretakers, ownership and operational changes and significance to Kent commerce and the greater community. Many of the buildings bestow a tale that stretches back to the late 1880s. Like the vintage Creamery Building on Meeker Street, between First and Second avenues south, that once housed the Carnation Milk Company. The cream-condensing plant rolled out its first can on Sept. 6, 1899. It soon expanded to include a tin can manufacturing facility, which turned out 50,000 cans a day.
There's also the Bouldron Building in the heart of West Meeker Street. Named after a prominent Kent contractor, the art deco building was architectural significant and historical important as a sign of recovery from the Great Depression.
The Clark Livery Stables, at the northeast corner of Second Avenue and Gowe Street, was once the spot where horses were bought and sold, where buggy and saddle horses were ready at all times. Over the years, the spot became Midway Motors (1937-44), a supermarket, a jewelry store and banks of different names, among other occupants. DAWN (Domestic Abuse Women's Network) owns and occupies it today.
Pedestrians, shoppers, even the curious visitor, can stroll along the sidewalks and capture the story behind each building.
"They can actually look at this and say, 'Wow, this is what was on this corner, this building, and see what it really looked like,' " Simpson said. "There's been so many changes. I mean, really, you look at any of these buildings … and (learn about the changes)."
Simpson, along with her husband Chuck, Eric Reiten and Tom Baines were among the GKHS members who made the project possible.
"It looks great," Baines said. "It's amazing how clear they (plaques) came out."
Simpson hopes to add other historical buildings to the plaque party, budget and contributing companies willing.
The GKHS and KDP also would like to create a walking tour map of the plaques.
Nancy Simpson, of the Greater Kent Historical Society and the city's Landmarks Commissioner, left, meets up with Mayor Dana Ralph, at the corner of 1st Avenue South and Gowe Street, where the building was once the First National Bank. Historical plaques describing 13 downtown Kent sites were unveiled last Friday. MARK KLAAS, Kent Reporter
Construction starts on YMCA in Kent
Safe Consumption Part 2: The Site
Kent woman, man die in double shooting on East Hill
Both lying on the ground; man had gun in his hand
King County Elections mails ballots for Aug. 6 primary
City Council races, fire measure in Kent
Kent man reportedly pimps more than 150 women in seven months
Prosecutors charge him with promoting prostitution; rape
Countywide birthday party sparks hope for girls aging out of foster care
Celebrate 18! was held by nonprofit Eileen & Callie's Place on Saturday.
King County Sheriff's Office nears completion of fatal motorcycle crash investigation
18-year-old man died June 28 after collision with Kent Police SUV
King County taxpayer tool shows how much Aug. 6 ballot measures will cost
Puget Sound Fire, county parks levies impact Kent residents
'Feedback loops' of methane, CO2 echo environmental problem beyond Washington
University of Washington among researchers of climate change's effects in global temperatures.
Kent couple seriously injured in hit-and-run while touring Spain
Family, friends establish a drive to cover medicals and bring them home
Downtown streets to close for Kent Cornucopia Days
6 p.m. July 11 to midnight July 14
8,000 Seattle to Portland bicyclists to ride through Kent Saturday
July 13 along West Valley Highway
Tukwila teen charged with vehicular homicide in Kent crash
16-year-old boy reportedly drove car in head-on collision that killed 13-year-old girl
Kent YMCA receives $250,000 from Delta Air Lines Foundation
New facility to open in September; fundraising goal at 95 percent
Sentencing range of 7 to 19 months if Tukwila teen convicted of vehicular homicide, other charges
16-year-old boy faces arraignment July 26 in King County Juvenile Court for Kent head-on crash
Sabhaya takes Miss Cornucopia crown
Kentridge grad bound for UW earns $3,000 scholarship from Kent Lions
Technical issue delays start of red-light cameras in Kent
Program start delayed from July 1 to yet-to-be determined date


The Action for Education Leadership Program of 2001 will require all school leaders to complete a Cultural Competency training starting in 2007. Eugene teachers already receive Cultural Competency training thanks to a previous grant. A Bill requested by the Governor would extend such training requirements to all licensed teachers in the State. The Bill passed the Senate on a 25 to 3 vote, and is awaiting a hearing in the House Education Committee. According a recent Associated Press story this week (Republicans may trap bill on 'cultural competency' for teachers), the Bill is unlikely to become law. This raises important issues that must receive ongoing attention on the local level. Nadia has years of experience dealing with issues like these.
We need to implement this into our school systems. This is one of the most important and painful issues facing every immigrant to this country! They need to have schools that respect & understand their children's background and ethnicity, comprehending the dynamic effects of policies and behaviors on children's self esteem. Cultural Competency promotes valuable assets and educational sensitivity to the cultures and religions of all students. It'll help to deter the bullying and hate crimes. We also need to recruit teachers from all diverse backgrounds. That would certainly restore the students' & families' confidence in the school system.
While I was researching and meeting with community members to gather information about their concerns and issues regarding the schools, one member of the Russian community approached and encouraged me to run for the School Board. He told me our children need to identify with some one like them in this position of leadership; someone with an accent, different skin color and language. Understanding the experiences of immigrant and diverse communities is key to effective policy making; that is one of my personal strengths and why I support efforts to foster cultural competency on every level.


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'Gangsta Granny' takes World Book Day prize at Queensbridge Primary School
Molly Phelan dressed up as Gangsta Granny, who won a prize for her costume at Queensbridge primary school. Picture: Tina Dixon
tina dixon
The Gazette was out and about taking photos of youngsters who dressed up to mark World Book Day on Thursday - and we have a pull-out picture special in the centre of today's edition.
Molly Phelan, right, dressed up as the David Walliams character Gangsta Granny, and was proud to win a prize for her amazing costume at Queensbridge Primary School.
The nine-year-old was awarded with a Roald Dahl book, George and the Marvellous Medicine, for having the best costume in her class.
Her mum Tina told the Gazette: "She was really excited because she said: 'I never win anything.'
"My other daughter wore the same costume last year and won a prize as well.
"Molly does like reading but it has to be the right book, at the minute her favourite author is David Walliams and she is working her way through his books. She's reading Awful Aunty at the moment. He uses the right words to engage with the child."


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