The Effect Of Aerobic Exercise Versus Inactivity On Nitric Oxide Concentration And Synthesis In And Elderly Population PDF Download

The population aged 65 and older in the United State is anticipated to increase by 53% by 2020. Aging is associated with changes in body composition and metabolism resulting in decreased maximal oxygen consumption (VO2max). In addition, gender, inactivity and diet in elderly may increase the risk of diseases such as cardiovascular disease, hypertension, and diabetes. Among the potential mechanisms associated with these changes may be reduced fat oxidation (FO). The immune system affects the factors described above, and in turn there are age-related changes in immune function which may lead to immunosenescence, thereby increasing the chance for infections and risks for some diseases. A common treatment for metabolic disturbances and immune function is statin drugs which decrease low density lipoprotein cholesterol (LDL-C) and reduce the risk of cardiovascular events and may reduce inflammatory processes.^The purpose of this dissertation was to determine if FO was reduced in elderly, specifically after correcting for other factors (e.g. diet, activity level, reduced VO2max etc.), and to investigate the impact FO has on immune responses to stress (exercise), and finally the benefits and consequences of statin therapy.Hypotheses: The following hypotheses were tested: 1) Elderly will have reduced fat oxidation, even after correction for the reduced maximal aerobic power, compared to young subjects. 2) The reduced fat oxidation in the elderly will be associated with reduced release and uptake of fats for metabolism, compared to young. 3) Aerobic exercise training in the elderly will improve fat oxidation, but will not reach the same level as the young. 4) Elderly will have an exaggerated immune response to exercise stress, which will be reduced by exercise training.^5) Statin therapy will significantly reduce fat oxidation.Protocol: To test these hypotheses, a series of studies were conducted. First, a retrospective analysis of total body fat oxidation from a randomized controlled study that was designed to test the effectiveness of an aerobic exercise program in elderly was completed. Second, a study was conducted to test total body fat oxidation, substrate delivery and immune responses to exercise in the elderly compared to young. In addition, an aerobic training program was conducted with the elderly to examine the total body fat oxidation, substrate delivery and immune response before and after training.^Third, compare elderly subjects on statin therapy with a matched control group for the above variables.Methods: In the first study, total body FO during progressive VO2max test on a cycle ergometer in sedentary young and elderly subjects was compared and then the effect of aerobic exercise training on FO in elderly determined. Healthy young women (n = 12), men (n = 10), elderly women (n = 44) and elderly men (n = 44) completed a VO2max test. Respiratory exchange ratio (RER = VCO2/ VO2) was measured as an estimate of FO. Elderly women and men (n =22 each) completed 8 weeks of aerobic exercise training (1 hr, 3 sessions/wk) on a cycle ergometer. For the second study, FO, VO2max, blood lipids, and the immune response to exercise in elderly (N=14) compared to young (n=16) and elderly prior to and after aerobic exercise training (12 wks, 3 sessions/wk for 1 hr).^VO2max and sustained submaximal (70% of VO2max) exercise tests were completed, as were pre and post-exercise blood samples. For the last study, elderly on statin therapy (n = 14) were compared to elderly control subjects (n = 14). FO was determined during maximal and sustained submaximal exercise protocol. Blood samples were drawn for lipid analysis and immune function.Results: VO2 and RER increased linearly with exercise intensity for young and elderly. RER was significantly higher in women than men (p = 0.001), in both young and elderly (p = 0.001). At submaximal VO2, RER increased as a function of VO2, and in elderly the slope increased significantly more than young (young men, RER = 0.12 VO2 + 0.71; elderly men, RER = 0.27 VO2 + 0.71; young women, RER = 0.33 VO2 + 0.54; elderly women, RER = 0.49 VO2 + 0.60, RER/L/min).^Exercise training in elderly increased VO2max (20% in elderly women, 30% in elderly men) and decreased RER at submaximal VO2 in elderly men (RER = 0.21 VO2 + 0.75), but not for elderly women. These data were confirmed in the second study where young had significantly higher VO2max than elderly (30.3 " 6.7 ml/min/kg vs. 16.7 " 6.2 ml/min/kg, p = 0.001). Young also had lower RER at all VO2's than elderly; however, not after correction for VO2max. Young had longer sustained exercise duration (45.5 " 17.6 min) than elderly pre-training (30.2 " 14.0 min). None of the differences between young and elderly could be accounted for by diet or daily activity levels. After 12 weeks of aerobic training in elderly, there was a significant increase in VO2max (14.53 " 3.68 to 24.54 " 4.57 ml/min/kg, p = 0.001).^After training, fasting total cholesterol (TC, 193 " 43 mg/dL) and low density lipoprotein cholesterol (118 " 34 mg/dL) did not change, while triglycerides (TG) (81 " 36 mg/dL to 115 " 59 mg/dL, p = 0.009) increased. After the VO2max test, post-training, RER (slope = 0.012 vs. 0.016, p = 0.001) and blood lactate (31%, p = 0.028) were significantly lower, while glucose increased (7%, p = 0.04). TG increased by the VO2max test (10-15%) both pre and post-training. After training, submaximal exercise time (58.3 " 27.3 min vs. 30.2 " 14.0 min, p = 0.02), glucose (20%, p = 0.038) and TG increased (6-18%, p = 0.024), while RER was reduced (0.90 " 0.03 vs. 1.00 " 0.03, p = 0.04). Although total caloric intake was higher in young, the balance of carbohydrates, fats and proteins was similar in young and elderly (about 53, 26 and 19%, respectively). In young subjects, no cytokines were increased after the VO2max test.^After the submaximal test in young, IL-1 & beta; (8 " 4 pg/ml) and IL-10 (0.7" 0.6 pg/ml) were not affected by exercise, while IL-6 increased significantly (1.9 " 1.3 to 2.9 " 2.2 pg/ml). In elderly after VO2max test, IL-1 & beta; increased (7.9 " 1.4 to 8.9 " 5.5 pg/ml, p = 0.05) and IL-10 decreased (0.6 " 1.1 to 0.8 " 1.5 pg/ml, p = 0.04). There were no differences between cytokines in young and elderly subjects (p = 0.38 to 0.63). For elderly there were no significant effects of exercise on IL-1 & beta;, IL-6 or IL-10 after 12 weeks of training. In the last study, RER was significantly higher in subjects taking statins during both the VO2max and submaximal tests, indicating reduced FO. Blood lipoprotein levels during exercise were not affected by statins nor were levels of glucose, lactate, or TG. However, free fatty acid levels were significantly elevated by exercise. Statin therapy did not affect IL-1 & beta; or TNF- & alpha;, but increased IL-6.^Conclusions: FO was reduced in the elderly before training, and remained lower than young even after VO2max and FO were increased after training, particularly in women. Elderly did not have reduced fat availability from blood or FO after correction for VO2max during exercise on a treadmill, which increased after training; and sustained exercise duration increased; however this 12 week aerobic training had little effect on the cardiovascular risk factors measured in this study. Neither young nor elderly healthy untrained subjects demonstrated inflammatory responses to exercise and training. In addition, cytokine production was not significantly altered in elderly. It appears that factors other than age may negatively impact the immune system in elderly subjects, i.e. diet, inactivity, diseases, etc.^Although statin therapy lowers baseline blood lipoproteins, its secondary effects need further consideration as FO was significantly reduced in elderly, and this could not be accounted for by diet, exercise, fitness or availability of fat from the blood.