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The effect of physical activity on muscle biology and health in statin-treated older individuals

Final Report Summary - ACTIVEAGING (The effect of physical activity on muscle biology and health in statin-treated older individuals)

The scientific objectives of the present project were to determine the effects of a muscle damaging resistance exercise with or without prior statin administration on skeletal muscle mass and function, muscle fatigue, muscle weakness, overall physical performance, resting energy expenditure, substrate metabolism, blood lipid profile, oxidative stress, proprioception, reaction time, functional fitness and on mobility.

Before embarking on the main project (i.e. much before the official start date of ACTIVEAGING but with the active engagement of the researcher) we decided to perform an independent study in order to ensure the validity of the main experimental design. In the independent study it was found that eccentric training markedly increased muscle strength and performance, REE, lipid oxidation, as well as decreased insulin resistance and blood lipid profile. It was reported that only 30 min of eccentric exercise per week for eight weeks was sufficient to improve human performance and health, rendering eccentric exercise a promising novel type of physical activity. The results of this project were very encouraging about the favourable effects of chronic eccentric exercise in various parameters of the human health and quality of life. The data of the independent study were published in Medicine and Science in Sports and Exercise 43(1):64-73, 2011. The paper is entitled 'A weekly bout of eccentric exercise is sufficient to induce health-promoting effects' (Paschalis V., Nikolaidis M. G., Theodorou A. A., Panayiotou G., Fatouros I. G., Koutedakis Y., Jamurtas A. Z.). Medicine and Science in Sports and Exercise (impact factor 3.8) is the official publication of the American College of Sports Medicine (ACSM) and is the most prestigious scientific journal in the field of sports medicine. Moreover, the manuscript was among the most popular publications of the journal during the first months of its publication, being the most viewed and most emailed manuscript during April 2011. The results of the independent study were also presented in the annual congress of the European College of Sport Science held in Antalya (Turkey) between 23 and- 26 July 2010. The presentation was entitled 'A weekly bout of eccentric exercise is sufficient to induce health-promoting effects' (Panayiotou G., Paschalis V., Nikolaidis M. G., Theodorou A. A., Fatouros I. G., Koutedakis Y., Jamurtas A. Z.). The time period during the independent study the Researcher was familiarised with the writing process of an original article along with the presentation of research data. Moreover, the Researcher was trained and familiarised with the preparation of a research proposal submitted for funding.

Based on the methodology and the results obtained from the first independent study, another independent study was also performed to validate the use of muscle biopsies. The aim of that study was very relevant to ACTIVEAGING project, namely to investigate the effects of vitamin C and E supplementation on muscle performance, blood and muscle redox status biomarkers and hemolysis in trained and untrained men after acute and chronic eccentric exercise. This manuscript is entitled 'No effect of antioxidant supplementation on muscle performance and blood redox status adaptations to eccentric training' (Theodorou A. A., Nikolaidis M. G., Paschalis V., Koutsias S., Panayiotou G., Fatouros I. G., Koutedakis Y. and Jamurtas A. Z.). This paper published in the American Journal of Clinical Nutrition 2011;93(6):1373-83 (impact factor 6.3) a journal with the highest impact factor in the field of Nutrition and the official journal of the American Society for Nutrition. In this investigation, muscle biopsies were collected in order the methodology of collecting and measuring redox status in muscle tissue to be used in the main project. However, the fact that in the main project the participant were elderly resulted in problems as detailed explained in the first periodic report of ActiveAging (i.e. the limited muscle mass of older individuals constrained us from collecting muscle tissue). In this study, the researcher had an active role familiarising with the methodology of the muscle biopsies as well as with the procedure of the muscle handling and storage after the biopsy.

In the main project, 24 males aged 60 - 75 years with total cholesterol concentration between 200 and 240 mg / dL and who had never received statin medications were enrolled. Participants attended two study visits over a period of a week. These visits included blood collection, questionnaires on physical activity, pain and quality of life, vital sign measurements, body measurements, gait analysis, proprioception assessment, muscle function and damage assessment as well as blood lipid profile and oxidative stress determination in blood. Participants also completed a cardiopulmonary exercise stress test on a treadmill. Participants then were randomly assigned to receive either 10 mg of atorvastatin or placebo on a daily basis for 6 months. All participants performed a muscle-damaging exercise bout and most of the baseline measurements were assessed up to a week. All physiological measurements and blood samplings were performed before, 1, 2, 3, 4, 5, 6 and 7 days after the maximal eccentric bout of exercise.

The results of the main project indicated that eccentric exercise, as well as the repeated bout of eccentric exercise, affected in a similar way the muscles of the control and statin therapy individuals, indicating that statin therapy does not affect negatively the response of muscles to the unaccustomed exercise. Moreover, statin therapy did not prevent the adaptation of the muscles to the repeated bout of eccentric exercise. Additionally, the blood lipid profile and the insulin sensitivity was affected similarly for both control and statin therapy group after bout 1 and about 2 of the eccentric exercise. It has to be noted that there was no difference between the two groups regarding their energy intake. It could be suggested from the results of the main project that elderly individuals who undergo statin therapy can participate in unaccustomed exercise activities and also they have the same advantages with their non-statin therapy counterparts regarding their performance and health during participation in resistance exercise. The data of this project were submitted for publication in the journal AGE (Manuscript ID: JAAA-S-11-00104) and the manuscript is under review. This journal is one of the most respected scientific journals in the field of aging and gerontology (impact factor 5.8). The manuscript is entitled 'No adverse effects of statins on muscle function and health-related parameters in the elderly: an exercise study' (Panayiotou G., Paschalis V., Nikolaidis M. G., Theodorou A. A., Deli C. K., Fotopoulou N., Fatouros I. G., Koutedakis Y., Sampanis M., Jamurtas A. Z.). Additionally, the researcher will present ACTIVEAGING project in the annual congress of the European College of Sport Science which will be held in Liverpool (Great Britain) between 6 and 10 July 2011. The presentation is entitled 'No adverse effects of statins on muscle function and health-related parameters in the elderly: an exercise study' (Panayiotou G., Paschalis V., Nikolaidis M. G., Theodorou A. A., Fotopoulou N., Fatouros I. G., Koutedakis Y., Jamurtas A. Z.) (Abstr. ID: 2091).

Due to the large volume of data relevant to proprioception and muscle function, it was decided these results to be published in a separate manuscript, which is currently under preparation. The unpublished results of these measurements indicate that gait biomechanics, proprioception and muscle function were affected in a similar way for both control and statin therapy individuals. Based on these findings, it is suggested that elderly individuals who undergo statin therapy can safely participate in physical and recreational activities, which in turns can help them maintain an adequate quality of life. The data of this project will be submitted for publication in the journal Gait and Posture. The manuscript will be entitled 'The effects of eccentric exercise on proprioception in elderly individuals undergoing statin treatment' (Panayiotou G., Paschalis V., Nikolaidis M. G., Theodorou A. A., Koutedakis Y., Jamurtas A. Z.). The data relevant to muscle function, proprioception and gait biomechanics will be also submitted for presentation in the 17th Congress of the European College of Sport Science congress (Bruges, Belgium, 4 - 7 July 2012).

Similarly with the data of the human movement analysis, the results of the redox status in the control and the statin treated individuals will be published separately in another manuscript, which is also under preparation. The results of these measurements indicate that indices of oxidative stress were affected in a similar way for both groups, indicating that elderly individuals undergoing statin treatment are not more susceptible to oxidative stress than the control group. Additionally, the antioxidant defense of the statin therapy group was not weaker than the control group and was affected in the same manner as the control group. The data of this project will be submitted for publication in the journal Archives of Biochemistry and Biophysics. The manuscript will be entitled 'The effects of eccentric exercise on redox status in elderly individuals undergoing statin treatment' (Panayiotou G., Nikolaidis M. G., Theodorou A. A., Paschalis V., Koutedakis Y., Jamurtas A. Z.). The results of the redox status will be submitted for presentation in the 37th Biochemistry and Medicinal Chemistry Congress (Sevilla, Spain, 4 - 9 September 2012).

Based on the novel findings derived from ACTIVEAGING project, a workshop was organised in the Department of Physical Education and Sport Science of the University of Thessaly in Trikala (15 September 2010). The workshop was attended by academic staff, researchers as well as a large number of Doctor of Philosophy (PhD) candidates and Master (MS) students of sport science, medicine and biology in Greece. The workshop included an extensive analysis of the study design employed, in order to teach interested parties in conducting appropriately similar in vivo integrative experiments in humans. Additionally, during the workshop the positive effects of performing eccentric exercise were analysed along with the risks that an individual may face participating in this special mode of exercise. Moreover, the advantages of isokinetic dynamometry were presented extensively.

Considering the fact that the side effects of statins are usually combined with limited physical activity, this renders the elderly a vulnerable group to develop muscle atrophy. In this project, the effects of muscle damaging eccentric exercise, applied in a control and in a statin therapy group of elderly individuals, were investigated. The results of the present investigation indicated that eccentric exercise, as well as the repeated bout of eccentric exercise, affected in a similar way both control and statin therapy individuals, indicating that statin therapy does not negatively affect the response of muscles to the unaccustomed exercise. Moreover, statin therapy did not prevent the muscle to adapt in response to the repeated bout of eccentric exercise. Therefore, elderly individuals who undergo statin therapy can participate in unaccustomed exercise activities and also they enjoy the same benefits with their non-statin therapy counterparts as regards with their performance and health enhancement during participation in resistance exercise regimes.