Sedentary lifestyles in modern obesogenic society produce several dysfunctions that cause chronic diseases in lederly population and this phenomenon is becoming a major public health problem. Regular physical activity has a profound effect on the expression of the potentials of human resilience, resulting in a decreased risk of chronic diseases. The identification of the biological mechanisms that are candidates for exercise-induced health benefits through biological pathways that are largely different from those targeted by common drugs, is highly relevant, since it might help to improve our knowledge of the pathophysiology of the chronic diseases in the sedentary population as well as to maximize the efficacy of physical activity interventions by implementing the best possible exercise dosage in older adults. For this purpose, the first aim of this project will be to identify the bioactive molecules and functional mechanisms that are candidates for exercise-induced health benefits. Moreover, in the view of more reliable, ecological and tailored approaches to counteract the problem of sedentary lifestyle, the second aim of this project will be to evaluate the effectiveness of an ecological exercise intervention in comparison to a traditional exercise intervention in sedentary elderly individuals.
The first aim of this projects will be to identify the bioactive molecules and functional mechanisms that are candidates for exercise-induced health benefits through biological pathways that are largely different from those targeted by common drugs. In the view of more reliable, ecological and tailored approaches to counteract the pandemic problem of sedentary lifestyle in elderly population, the second aim of this project will be to evaluate the effectiveness of an ecological exercise intervention (EEI) in comparison to traditional exercise intervention (TEI) in sedentary older adults. Introduction: Despite our society has developed several advances in technology and medicine, the human genetic framework is largely tailored to support the physical activity (PA) patterns of hunter-gatherer societies living 2.5 million years ago, for which food finding was obligatorily associated to PA. The energy expenditure of hunter-gatherers (1,500 kcal/day) is similar to 3h/day of moderate-to-vigorous PA (MVPA). Contrarily, technological improvements have influenced the dramatic drop in human PA levels: 1/3 of adults worldwide are currently inactive, and the endemic inactivity trend starts in early life. Indeed, sedentary behaviors in contemporary obesogenic environments trigger dysfunctions that cause chronic diseases and this phenomenon is becoming a major public health problem. Interestingly, regular PA has a profound effect on the expression of the potentials of human resilience, resulting in numerous positive adaptations and decreased risk of chronic diseases. Protective role of exercise on cardiovascular disease risk factors: There is strong epidemiological evidence indicating that regular PA is associated with reduced rates of cardiovascular disease (CVD), hypertension, stroke, metabolic syndrome and Type 2 diabetes. Moreover, a dose-response of PA is usually observed in the general population. It is important to note, that exercise training has an improving effect on endothelial function. The polypill-like effect of Exercise: Despite, in the last 40 years the pandemic increase of cardio-metabolic diseases has paralleled the advances in medicine, CVD remains the leading cause of death worldwide. In this complicated scenario, Wald and Law first described a combination pill for CVD prevention, which they called a "polypill". These authors claimed that CVD could be reduced by 88% and strokes by 80% if all those over 55 years of age were given a polypill containing statin, low-dose aspirin, and folic acid. This controversial and provocative approach of "medicalizing" the population is not possible and not ethical, but polypill-like benefits are achievable with a drug-free intervention, regular PA. It is worth of mention that the identification of the bioactive molecules and biological mechanisms that are candidates for exercise-induced health benefits through biological pathways that are largely different from those targeted by common drugs, is highly relevant, since it might help to improve our knowledge of the pathophysiology of the chronic diseases in the sedentary eldely population as well as to maximize the efficacy of PA interventions by implementing the best possible exercise dosage, resulting in optimal circulating levels of "health" molecules. The exercise polypill: Skeletal-muscle fibers can produce a plethora of secreted factors, including proteins, growth factors, cytokines, with such secretory capacity increasing during active exercise, myogenesis and muscle remodeling. Muscle-derived molecules exerting either paracrine or endocrine effects are termed "myokines" and can be consider the exercise polypill. Since regular exercise has protective effects on cardiovascular diseases and, interestingly, it is more protective than expected based on the improvement of traditional risk factors (blood lipids, hypertension, diabetes) it is easy to speculate that additional positive effects could be mediated by myokines on targets such as adipose tissue or liver. For example, IL-6 is probably the myokine prototype because its level increases with exercise intensity and duration. Systemic low-level inflammation is a cardinal feature of cardio-metabolic diseases, and it can be attenuated by the cumulative effect of regular exercise bouts, during which the muscle releases IL-6 which creates a healthy milieu by inducing the production of other anti-inflammatory cytokines. Another prototype of contraction-induced myokine is IL-15, with resistance exercise stimulating its secretion. Muscle-derived IL-15 is one of the mediators of the anti-obesity effects of exercise. Recent research identified a novel PGC-1 -induced myokine called iriscin. Iriscin is associated with improved aerobic fitness in cardiac patients, muscle mass, and metabolic factors in healthy people, and neurogenesis in animal models. Secreted protein acidic and rich in cysteine (SPARC) is a matricellular glycoprotein released into the bloodstream by skeletal muscle in response to aerobic exercise plays a pivotal role in adipocyte differentiation and adipose tissue turnover. Myostatin, is a potent muscle-growth inhibitor, endurance or resistance exercise downgrade myostatin expression. Another class of molecules which are potentially up-regulated with regular exercise and could have additional effects on the protective effects of regular exercise are neurotrophins. Among them, brain-derived neurotrophic factor (BDNF) is the most affected by exercise. Increased levels of BDNF are well documented, providing mechanistic support for a beneficial exercise effect in cognitive function. Furthermore, BDNF increases phosphorylation enhancing fatty acid oxidation and glucose utilization in skeletal muscle.The emerging general feature is that During physical inactivity, adipose tissue secretes pro-inflammatory cytokines, which can lead to development of metabolic and cardiovascular diseases, such as T2DM and atherosclerosis (Iyer et al., 2010). The study of myokines as potential biomarkers for effectiveness of exercise is an attractive approach to develop better physical protocols to apply to the elderly population. Intervention approaches: Sedentary behaviors in older adults are strongly associated with systemic dysfunctions that cause chronic diseases and this phenomenon is becoming a major public health problem. Moreover, the recognized polypill-like effect of exercise, needs further research in order to identify the biological mechanisms that are candidates for exercise-induced health benefits. Furthermore, it is necessary to maximize the efficacy of PA interventions by implementing the best possible exercise dosage. In this complicated scenario, Owen and colleagues explain in their scientific contribution "Adults' Sedentary Behavior Determinants and Interventions" the relevant phases of the behavioral epidemiology research strategy on sedentary behavior for children and adults, highlighting several strengths of the evidence relevant to interventions and public health initiatives. Ecological-Exercise-Intervention: One of the goals of public health interventions would be to reduce total sedentary time and also to increase the number of breaks in sedentary time. A starting point for this 'Ecological-Exercise-Intervention'(EEI), would be to limit sitting time to no more than 2 hours/day, and to stand up and move after 30 minutes of continuous sitting. In accordance with several epidemiologic evidences light-intensity activities would be encouraged to substitute sedentary time (e.g., standing up while talking on the telephone, ironing while watching TV). Taking into consideration the guidance provided by ecologic models of health behavior evidences about specific constructs to guide EEI may be derived from behavioral research on physical activity. However, further studies are needed to clarify the feasibility, acceptability, and effectiveness of EEI in young and adult populations. On this matter, promising results have been observed in studies targeting increases in daily walking. Moreover, systematic evaluations of these "natural approaches" could be highly informative, especially through assessing whether changes in sedentary time actually do result.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
180
'Ecological-Exercise-Intervention'(EEI), would be to limit sitting time to no more than 2 hours/day, and to stand up and move after 30 minutes of continuous sitting. In accordance with several epidemiologic evidences light-intensity activities would be encouraged to substitute sedentary time (e.g., standing up while talking on the telephone, ironing while watching TV).
University of Verona
Verona, Italy
Measure of strandars healthy-related biochemical parameters
Blood samples will be collected two times: 1) between 7:00 and 9:00 am, following overnight fasting, 48h distant from the last exercise session and 2) immediately after a training session. After centrifugation, they will be divided in different aliquots of appropriate amount and stored a -80°C in order to: measure triglycerides, total cholesterol, blood glucose, aspartate transaminase, alanine transaminase, creatinine
Time frame: through study completion, an average of 8 months
Measure of Daily Energy Expenditure
Each participant will be outfitted with an Actiheart device allowing heart rate and acceleration data to be simultaneously recorded 24 hours a day for 7 consecutive days. Health-related quality of life: The Italian version of the SF-36 health survey will be administrated before and after the interventions.
Time frame: through study completion, an average of 8 months
Measure of the appendicular muscle mass
Magnetic resonance imaging (MRI) will be performed using a 1.5 Tesla MRI system. T1-weighted images of the lower limbs will be acquired supine with the legs extended. On the basis of a signal-intensity threshold, muscle borders will be selected to delineate and differentiate muscle, fat, and connective tissue. In the thighs area, the vastus lateralis (VL), vastus medialis, vastus intermedius, and rectus femoris will be traced in each image and in combination made up the quadriceps. Quadriceps muscle volumes will be calculated by summing the areas of all the slices.
Time frame: through study completion, an average of 8 months
Measure of Musle architecture
In the thigh, sagittal ultrasound images of the VL muscle will be recorded with a GE ultrasound system (GE Logiq-7) equipped with an 8-12 MHz linear transducer. Images will be obtained with a 90° flexion of hip and knee, at 50% of femur length corresponding to the mid-belly of the VL muscle. The pennation angle of the VL fascicles will be measured as the angle between the VL muscle fascicles and the deep aponeurosis of the insertion.
Time frame: through study completion, an average of 8 months
Measure of systemic vascular function
The passive limb movement protocol consisted of 60 s of resting baseline femoral blood flow data collection, followed by 60 s of passive knee extension and flexion with the same measure. Blood velocity will be analyzed with 1 Hz resolution on the Doppler ultrasound system (GE Logiq-7) for 60 s at rest and second by second for the first 60 s following the initiation of PLM.
Time frame: through study completion, an average of 8 months
Measure of cirulating level of hormones
Blood samples will be collected two times: 1) between 7:00 and 9:00 am, following overnight fasting, 48h distant from the last exercise session and 2) immediately after a training session. After centrifugation, they will be divided in different aliquots of appropriate amount and stored a -80°C in order to: measure cirulatin glevels of hormones such as: GH, IGF-1, IGFBP3, insulin and cortisol; the pro- and anti-inflammatory markers, C Reactive Protein (CRP), IL-1, IL-6 and IL-1ra; and of the sex-hormones testosterone, oestradiol, oestrone and sex hormone-binding globulin (SHBG);
Time frame: through study completion, an average of 8 months
Measure of cirulating bioactive markers
Blood samples will be collected two times: 1) between 7:00 and 9:00 am, following overnight fasting, 48h distant from the last exercise session and 2) immediately after a training session. After centrifugation, they will be divided in different aliquots of appropriate amount and stored a -80°C in order to measure circulating miRNA, PGC-1, Myonectin, Musclin, Sparc, Myostatin, BDNF, VEGF, and BDNF
Time frame: through study completion, an average of 8 months
Measure of cardio-metabolid health
Measurements of blood pressure will be performed with standard auscultatory and mercury sphygmomanometer technique. From a fasted venous blood sample Glucose, high- and low-density lipoprotein will be measured on a Cobas c501 (Roche Diagnostics GmbH, Mannheim, Germany), using proprietary reagents. Body anthropometrics will be measured with a standard protocol: body mass, height, body mass index calculation (BMI = body mass / height2), percent of body fat (7 skinfolds approach), waist and hip circumferences.
Time frame: through study completion, an average of 8 months
Measure of exercise capacity
To determine exercise capacity the subjects will perform an incremental walking maximal exercise trial (rest, 25%, 50%, 75%, and 100% of maximal exercise capacity). Breath-by-breath O2 expiratory airflow will be continuously recorded at rest, and during the exercise trial.
Time frame: through study completion, an average of 8 months
Measure of Lower limbs neuromuscular control
The force and EMG envelope rate of development during a maximum voluntary contraction and a tetanic stimulation will be compared in order to estimate the role of central command flow to the muscle in changing the efficiency of the tension development at the tendon. The maximal voluntary contraction will be started after a visual command will be done.
Time frame: through study completion, an average of 8 months
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.