Physical activity and telomere length: Impact of aging and potential mechanisms of action.

Telomeres protect the integrity of information-carrying DNA by serving as caps on the terminal portions of chromosomes. Telomere length decreases with aging, and this contributes to cell senescence. Recent evidence supports that telomere length of leukocytes and skeletal muscle cells may be positively associated with healthy living and inversely correlated with the risk of several age-related diseases, including cancer, cardiovascular disease, obesity, diabetes, chronic pain, and stress. In observational studies, higher levels of physical activity or exercise are related to longer telomere lengths in various populations, and athletes tend to have longer telomere lengths than non-athletes. This relationship is particularly evident in older individuals, suggesting a role of physical activity in combating the typical age-induced decrements in telomere length. To date, a small number of exercise interventions have been executed to examine the potential influence of chronic exercise on telomere length, but these studies have not fully established such relationship. Several potential mechanisms through which physical activity or exercise could affect telomere length are discussed, including changes in telomerase activity, oxidative stress, inflammation, and decreased skeletal muscle satellite cell content. Future research is needed to mechanistically examine the effects of various modalities of exercise on telomere length in middle-aged and older adults, as well as in specific clinical populations.

Physical Activity Domains/Recommendations and Leukocyte Telomere Length in U.S. Adults.

PURPOSE: The purpose of this study was to examine the associations between different physical activity (PA) domains, PA recommendations, and leukocyte telomere length (LTL) using data from a nationally representative sample of U.S. adults in the National Health and Nutrition Examination Survey, 1999-2002. METHODS: A total of 6933 U.S. adults (3402 men, 3531 women; age range: 20-84 yr) who completed demographic, general health and PA questionnaires and provided a blood sample were included in the analyses. Multivariable-adjusted linear regression models were used to determine associations between PA (domain-specific PA [household/yard work PA, transportation PA, moderate leisure time PA (LTPA), and vigorous LTPA], total moderate PA and PA recommendation groups), and log-transformed LTL adjusting for age, gender, education, cigarette smoking, alcohol consumption, and body mass index. RESULTS: On average, an increase of 1 h·wk of vigorous LTPA was associated with a 0.31% (P < 0.001) longer LTL, and an increase of 1 h·wk of household/yard work PA was associated with a 0.21% (P = 0.03) shorter LTL while adjusted for sociodemographic and health behavior covariates. Neither transportation PA nor moderate LTPA was significantly associated with LTL. In addition, compared with not meeting the PA recommendation (<150 min·wk), exceeding the recommended PA levels (≥300 min·wk) was positively associated with longer LTL (P = 0.04), whereas there was no difference in telomere length between those not meeting versus those meeting the PA recommendation (150-299 min·wk). CONCLUSION: Greater engagement in vigorous LTPA and exceeding the PA recommendation may have a protective effect against telomere shortening. Future studies should examine the association between PA and LTL by exploring potential mediators such as sedentary behavior, genetics, nutrition, and chronic diseases.

Regional adipose tissue hormone/cytokine production before and after weight loss in abdominally obese women.

OBJECTIVE: To compare the regional differences in subcutaneous adipose tissue hormone/cytokine production in abdominally obese women during weight loss. METHODS: Forty-two abdominally obese, older women underwent a 20-week weight loss intervention composed of hypocaloric diet with or without aerobic exercise (total energy expenditure: ∼2800 kcal/week). Subcutaneous (gluteal and abdominal) adipose tissue biopsies were conducted before and after the intervention. Adipose tissue gene expression and release of leptin, adiponectin, and interleukin 6 (IL-6) were determined. RESULTS: The intervention resulted in significant weight loss (-10.1 ± 0.7 kg, P < 0.001). At baseline, gene expression of adiponectin were higher (P < 0.01), and gene expression and release of IL-6 were lower (both P < 0.05) in abdominal than in gluteal adipose tissue. After intervention, leptin gene expression and release were lower in both gluteal and abdominal adipose tissue compared to baseline (P < 0.05-0.01). Abdominal, but not gluteal, adipose tissue adiponectin gene expression and release increased after intervention (both P < 0.05). CONCLUSION: A 20-week weight loss program decreased leptin production in both gluteal and abdominal adipose tissue, but only increased adiponectin production from abdominal adipose tissue in obese women. This depot-specific effect may be of importance for the treatment of health complications associated with abdominal adiposity.

Effects of exercise training on indicators of adipose tissue angiogenesis and hypoxia in obese rats.

OBJECTIVE: To investigate the effects of obesity and exercise training on regional adipose tissue angiogenesis and hypoxia markers in rats. METHODS: Lean (Fa/Fa) and obese (fa/fa) male Zucker rats at 2 months of age were randomly assigned to a sedentary or an exercise training group (lean sedentary: n=7, lean exercise: n=8, obese sedentary: n=7, obese exercise: n=8). The exercise group walked on a rat treadmill 5 times per week for 8 weeks. Inguinal and epididymal adipose tissue vascular endothelial growth factor A (VEGF-A) and lactate levels were determined. RESULTS: There were significant effects of obesity in increasing inguinal (P<0.001) and epididymal (P<0.05) adipose tissue VEGF-A, and a significant effect of exercise training in increasing epididymal adipose tissue VEGF-A (P<0.05). There was a significant effect of obesity in increasing inguinal adipose tissue lactate levels (P<0.001). Compared to lean sedentary animals, obese sedentary animals had significantly higher epididymal adipose tissue lactate levels (P<0.001); compared to obese sedentary animals, obese exercise rats had significantly lower epididymal adipose tissue lactate levels (P<0.05). CONCLUSIONS: Exercise training increased adipose tissue VEGF-A, an important factor of tissue angiogenesis, and lowered adipose tissue lactate, an indicator of adipose tissue hypoxia in obese rats. However, these effects are depot-specific and only observed in intra-abdominal adipose tissue.

Physical function improvements after laparoscopic Roux-en-Y gastric bypass surgery.

BACKGROUND: Obesity is a risk factor for impaired physical function and disability, with the degree of impairment most compromised in extreme obesity. Mild-to-moderate weight loss has been shown to improve function in older adults. The impact of laparoscopic Roux-en-Y gastric bypass surgery on weight loss and physical function in morbidly obese individuals was assessed. METHODS: This longitudinal, observational study followed up 28 morbidly obese men and women (body mass index > or = 40.0 kg/m(2)) for 12 months after laparoscopic Roux-en-Y gastric bypass. Physical function (self-report using the Fitness Arthritis and Seniors Trial disability questionnaire; performance tasks using the Short Physical Performance Battery and a lateral mobility task); strength (maximal isometric knee torque); and body composition measured using bioelectrical impedance were determined before surgery (baseline) and at 3 weeks, 3 months, 6 months, and 12 months after surgery. RESULTS: The 12-month weight loss was 34.2% (excess weight loss 59.8%), with a mean fat mass loss of 46 kg and a loss of fat free mass of 6.6 kg. The performance tasks and self-reported questionnaire scores had improved by 3 months after surgery compared with baseline, with selected measures showing less impairment and disability in as few as 3 weeks after surgery. Muscle quality, as measured using the maximal torque per kilogram body weight, was greater at 6 months than at baseline. CONCLUSION: The results of our study have shown that in morbidly obese individuals with a high risk of mobility impairments, surgical procedures to reduce body weight increase mobility and improve performance of daily activities in as few as 3 weeks after gastric bypass surgery.

Weight regain is related to decreases in physical activity during weight loss.

PURPOSE: To examine whether adaptations in physical activity energy expenditure (PAEE) and resting metabolic rate (RMR) during weight loss were associated with future weight regain in overweight/obese, older women. RESEARCH METHODS AND PROCEDURES: Thirty-four overweight/obese (BMI = 25-40 kg x m(-2)), postmenopausal women underwent a 20-wk weight loss intervention of hypocaloric diet with (low- or high-intensity) or without treadmill walking (weekly caloric deficit was approximately 11,760 kJ), with a subsequent 12-month follow-up. RMR (via indirect calorimetry), PAEE (by RT3 accelerometer), and body composition (by dual-energy x-ray absorptiometry) were measured before and after intervention. Body weight and self-reported information on physical activity were collected after intervention and at 6 and 12 months after intervention. RESULTS: The intervention resulted in decreases in body weight, lean mass, fat mass, percent body fat, RMR, and PAEE (P < 0.001 for all). Weight regain was 2.9 +/- 3.3 kg (-3.1 to +9.2 kg) at 6 months and 5.2 +/- 5.0 kg (-2.3 to +21.7 kg) at 12 months after intervention. The amount of weight regained after 6 and 12 months was inversely associated with decreases in PAEE during the weight loss intervention (r = -0.521, P = 0.002 and r = -0.404, P = 0.018, respectively), such that women with larger declines in PAEE during weight loss experienced greater weight regain during follow-up. Weight regain was not associated with changes in RMR during intervention or with self-reported physical activity during follow-up. CONCLUSION: This study demonstrates that although both RMR and PAEE decreased during weight loss in postmenopausal women, maintaining high levels of daily physical activity during weight loss may be important to mitigate weight regain after weight loss.

The metabolic syndrome is associated with circulating adipokines in older adults across a wide range of adiposity.

BACKGROUND: Circulating levels of adipokines are elevated with adiposity and are closely linked with the clustering of traditional metabolic risk factors for cardiovascular disease. The purpose of this study was to examine the relationship of metabolic syndrome to several adipokines and the role of total and visceral adiposity in influencing this relationship in older adults. METHODS: A cross-sectional analysis was conducted including 1914 individuals aged 70-79 years without cardiovascular disease or type 2 diabetes. The metabolic syndrome was defined by the updated Adult Treatment Panel III criteria. Circulating levels of leptin, adiponectin, plasminogen activator inhibitor type 1 (PAI-1), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), and C-reactive protein (CRP) were measured. Body composition and abdominal visceral fat area were determined. RESULTS: Both the presence of metabolic syndrome and the number of metabolic syndrome components were associated with higher levels of leptin, PAI-1, IL-6, TNF-alpha, and CRP and with lower levels of adiponectin (all p <.0001). The odds ratios for the prevalence of metabolic syndrome associated with adipokines were attenuated after adjustment for total fat mass and/or visceral fat area, but remained significant. Levels of leptin, PAI-1, IL-6, and TNF-alpha were higher (all p <.05 to p <.0001), and adiponectin was lower (all p <.0001), in persons with, compared to those without, metabolic syndrome within each tertile of percent body fat. CONCLUSION: The metabolic syndrome is associated with adipokines in older adults across a wide range of adiposity, including in those with low or normal overall fatness.

Lifelong caloric restriction and interleukin-6 secretion from adipose tissue: effects on physical performance decline in aged rats.

We investigated whether caloric restriction (CR) improves physical performance in a rodent model of aging, and whether this effect is accompanied with a decrease in visceral adipose tissue production of proinflammatory cytokines. Body composition, standardized physical performance measures, as well as in vitro visceral adipose tissue cytokine secretion and circulating levels of an inflammatory marker were cross-sectionally assessed in ad libitum (AL)-fed and lifelong CR Fischer 344 x Brown Norway male rats aged 18, 24, and 29 months. Fat to lean mass ratio increased and physical performance declined with age in the AL rats. Compared to AL rats, CR rats had lower fat mass, fat to lean ratio, adipose tissue secretion of interleukin-6, and circulating levels of C-reactive protein, and higher physical performance scores. Therefore, CR may be an effective intervention for improving functional status into advanced age and is perhaps mediated via a reduction in adipose tissue-generated proinflammatory cytokine production.

Chronic inflammation: role of adipose tissue and modulation by weight loss.

Chronic inflammation has been linked with an increased risk of type 2 diabetes and cardiovascular disease. As an endocrine and inflammatory organ, adipose tissue is an important source of circulating pro-inflammatory cytokines. Current evidence strongly supports that chronic inflammation is associated with enlarged body fat mass. Moreover, inflammation is independently linked with abdominal, especially visceral fat mass, possibly due to the regional variation in adipose tissue cytokine production. In addition to pharmacological approaches, lifestyle modifications have been advocated for the treatment of chronic inflammation. A number of studies have indicated that either weight loss via energy restriction, or energy restriction plus other strategies (aerobic exercise, behavioral counseling, and liposuction), could reduce chronic inflammation. While the amount of weight loss tends to be important, exercise and other strategies may have additional effects. A few studies have reported weight loss effects on adipose tissue cytokine production. Weight loss reduces subcutaneous adipose tissue production of pro-inflammatory cytokines (i.e. interleukin 6, tumor necrosis factor alpha) and increases adipose expression of anti-inflammatory cytokines (i.e. interleukin 10, interleukin 1 receptor antagonist). More studies are needed to investigate the role of regional adipose tissue cytokine production in regulation of inflammation and the modulating effects of weight loss.

Vitamin C supplementation affects oxidative-stress blood markers in response to a 30-minute run at 75% VO2max.

Vitamin C supplementation (VC) (either 500 or 1000 mg/d for 2 wk) was compared to a placebo treatment (P) to ascertain if VC could influence oxidative stress. Twelve healthy males (25 +/- 1.4 y) were randomly assigned in a counter-balanced design with a 2-wk period between treatments. Data were analyzed using repeated measures ANOVA. Exercise intensity measures (VO(2), RER, RPE, HR, lactate) were similar across treatments. Resting blood oxidative-stress markers were unaffected by treatment. Exercise decreased total blood glutathione (TGSH) and reduced glutathione (GSH) and increased oxidized glutathione (GSSG) (P < 0.01) independent of treatment. Protein carbonyls (PC) increased 3.8 fold in the P (P < 0.01). VC attenuated the PC exercise response in a dose-dependent manner ( P < 0.01). Thiobarbituric acid reactive substances (TBARS) was not influenced by exercise (P = 0.68) or VC. These data suggest that VC supplementation can attenuate exercise-induced protein oxidation in a dose-dependent manner with no effect on lipid peroxidation and glutathione status.

Behavioural treatments for chronic systemic inflammation: effects of dietary weight loss and exercise training.

Persistent low-grade inflammation, as indicated by higher circulating levels of inflammatory mediators such as C-reactive protein, interleukin-6 and tumour necrosis factor-alpha, is a strong risk factor for several chronic diseases. There are data indicating that decreasing energy intake and increasing physical activity may be effective therapies for reducing overall inflammation. Evidence is strong that circulating levels of inflammatory markers are elevated with total and abdominal obesity, possibly owing to a higher secretion rate of cytokines by adipose tissue in obese people. Moreover, very-low-energy dietary weight loss reduces both circulating markers of inflammation and adipose-tissue cytokine production. Data from several large population-based cohorts show an inverse association between markers of systemic inflammation and physical activity or fitness status; small-scale intervention studies support that exercise training diminishes inflammation. Dietary weight loss plus exercise is likely more effective than weight reduction alone in reducing inflammation. To date, data from randomized, controlled trails designed to definitively test the effects of weight loss or exercise training, or both, on inflammation are limited. Future studies are required to define the amount of weight loss needed for clinically meaningful reductions of inflammation; in addition, fully powered and controlled studies are necessary to clarify the effect of exercise training on chronic, systemic inflammation.

Abdominal adipose tissue cytokine gene expression: relationship to obesity and metabolic risk factors.

Adipose tissue is a major source of inflammatory and thrombotic cytokines. This study investigated the relationship of abdominal subcutaneous adipose tissue cytokine gene expression to body composition, fat distribution, and metabolic risk during obesity. We determined body composition, abdominal fat distribution, plasma lipids, and abdominal subcutaneous fat gene expression of leptin, TNF-alpha, IL-6, PAI-1, and adiponectin in 20 obese, middle-aged women (BMI, 32.7 +/- 0.8 kg/m2; age, 57 +/- 1 yr). A subset of these women without diabetes (n = 15) also underwent an OGTT. In all women, visceral fat volume was negatively related to leptin (r = -0.46, P < 0.05) and tended to be negatively related to adiponectin (r = -0.38, P = 0.09) gene expression. Among the nondiabetic women, fasting insulin (r = 0.69, P < 0.01), 2-h insulin (r = 0.56, P < 0.05), and HOMA index (r = 0.59, P < 0.05) correlated positively with TNF-alpha gene expression; fasting insulin (r = 0.54, P < 0.05) was positively related to, and 2-h insulin (r = 0.49, P = 0.06) tended to be positively related to, IL-6 gene expression; and glucose area (r = -0.56, P < 0.05) was negatively related to, and insulin area (r = -0.49, P = 0.06) tended to be negatively related to, adiponectin gene expression. Also, adiponectin gene expression was significantly lower in women with vs. without the metabolic syndrome (adiponectin-beta-actin ratio, 2.26 +/- 0.46 vs. 3.31 +/- 0.33, P < 0.05). We conclude that abdominal subcutaneous adipose tissue expression of inflammatory cytokines is a potential mechanism linking obesity with its metabolic comorbidities.

Oxidative stress response in normal and antioxidant supplemented rats to a downhill run: changes in blood and skeletal muscles.

The purpose of this study was to determine if changes in oxidative stress biomarkers in blood and skeletal muscles are similar in normal and antioxidant supplemented rats after a downhill run. Sixty-six male Sprague-Dawley rats were pretreated with a normal rat diet or diet + antioxidants (2,000 mg vitamin C + 1,000 IU vitamin E/kg diet) for 2 weeks. Exercised rats ran 90 min on a rodent treadmill at a speed of 16 m/min at -16 degrees grade. Rats were sacrificed either at rest, immediately, 2 hrs, or 48 hrs postexercise. Malondialdehyde (MDA) and protein carbonyl (PC) concentrations and glutathione status in blood, vastus lateralis (white fast-twitch), vastus intermedius (red fast-twitch), and soleus (slow-twitch) muscles were determined. A significant increase from rest in PC occurred in plasma, vastus intermedius and soleus muscle 2 hrs after the downhill run (p < 0.05), with no changes observed at any other times postexercise. Antioxidant supplementation significantly decreased PC concentrations in both vastus intermedius and soleus muscles at all times combined (p < 0.05). MDA and glutathione status in blood and muscles were unaffected by either the downhill run or antioxidant treatment. For PC and MDA, the concentrations were lower in blood as compared to skeletal muscle, with the opposite finding for oxidized glutathione; however, the pattern of response postexercise was similar. These data indicate that (a) PC, but not MDA or oxidized glutathione, is elevated transiently following downhill running in male rats; (b) the elevation in PC postexercise occurs in plasma, vastus intermedius, and soleus muscles; (c) antioxidant therapy can attenuate PC in vastus intermedius, and soleus muscles; and (d) while the concentrations of oxidative stress biomarkers differ between blood and the various skeletal muscles, the pattern of response postexercise is similar.

The metabolic syndrome in obese postmenopausal women: relationship to body composition, visceral fat, and inflammation.

The purpose of this study was to investigate whether aerobic fitness, body composition, body fat distribution, and inflammation are different in obese postmenopausal women with and without the metabolic syndrome (MS), and whether the severity of MS is associated with these characteristics. Fifty-eight women (age, 59 +/- 1 yr; body mass index, 33.0 +/- 0.6 kg/m2)completed testing of maximal aerobic capacity, body composition (fat mass, lean mass, and percent body fat), body fat distribution (sc and visceral fat areas, and regional adipocyte sizes), and inflammation (C-reactive protein, IL-6, and TNF-alpha,and their soluble receptors). Lean mass (44.4 +/- 0.9 vs. 41.2 +/- 0.9 kg; P < 0.05), visceral fat area (180 +/- 10 vs. 135 +/- 7 cm2; P <0.001), and plasma soluble TNF receptor 1 (sTNFR1; 860 +/- 25 vs. 765 +/- 42 pg/ml; P < 0.05) were higher in women with the MS(n = 27) than in those without the MS (n = 31). The number of MS components was directly related to weight, body mass index, fat mass, lean mass, visceral fat area, and plasma sT-NFR1. We conclude that obese older women with the MS are characterized by high lean mass, high visceral fat, and elevated sTNFR1, and the severity of the MS is associated with body composition, visceral adiposity, and inflammation.