Physical Fitness as Klotho Protein Stimulator.

Study Overview
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Brief Summary
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FIT-AGING will determine the effect of different exercise modalities on α-Klotho protein (primary outcome) in sedentary healthy adults. FIT-AGING also investigate the physiological consequences of activating Klotho gene (secondary outcomes).

Detailed Description
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Aims: The plasma Klotho protein concentration (α-Klotho protein), which is considered a powerful biomarker of longevity, makes it an attractive target as an anti-aging therapy against functional decline, sarcopenic obesity, metabolic and cardiovascular diseases, osteoporosis, and neurodegenerative disorders. Physical exercise and physical fitness, could be α-Klotho protein activators through biochemical process. FIT-AGING will determine the effect of different exercise modalities on α-Klotho protein (primary outcome) in sedentary healthy adults. FIT-AGING also investigate the physiological consequences of activating Klotho gene (secondary outcomes). Methods: FIT-AGING will recruit 60 sedentary, healthy, adults (50% women) aged 40-65 years. Eligible participants will be randomly assigned to a non-exercise group to the usual control group (n=15), physical activity recommendation from American College of Sport Medicine, World Health Organization and American Heart Association group (n=15), High Intensity Interval Training group (n=15)) and Whole-Body Electromyostimulation group (n=15). Laboratory measures completed at baseline and 12 weeks later, include α-Klotho protein concentration, physical fitness (cardiorespiratory fitness, muscular strength), body composition, resting metabolic rate, hearth rate variability (HRV), health blood biomarkers, free-living physical activity, sleep habits reaction time, cognitive variables and health-related questionnaires. The investigators will also obtain dietary habits data and cardiovascular disease risk factors.

Official Title
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Physical Fitness as Klotho Protein Stimulator; Antiaging Effects of New Training Methods (FIT-AGING).

Conditions
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Physical Activity, Aging

Intervention / Treatment
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* Other: PAR
* Other: HIIT
* Other: WB-EMS


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age: 40-65 years BMI:18.5-35 kg/m2 Not engaged in regular physical activity >20min on >3days/week Not participating in a weight loss programme Stable weight over the last 5 months (body weight changes>5kg) Participant must be capable and willing to provide consent, understand exclusion criteria and accept the randomized group assignment Normal electrocardiogram Exclusion Criteria: History of cardiovascular disease Diabetes Pregnancy or planning to get pregnant during study period Beta blockers or benzodiapezins use Taking medication for thyroid Other significant conditions that are life-threatening or that can interfere with or be aggravated by exercise Unwillingness to either complete the study requirements or to be randomized into control or training group A first-degree relative with history of cancer

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Control<br>Non-Exercise group. We will provide general advices to control group participants thought an information meeting performed by a graduate in Sport Sciences. It will recommended to follow the physical activity recommendations for adults provided by World Health Organization | |
| Experimental: PAR group<br>The volume in PAR is based on the minimum physical activity recommended (150min/week at moderate intensity). Intensity selected for PAR aerobic training is 60-65% HRres. Strength intensity selected was 40-50% of 1 RM. Frequency. PAR group will train 3 days/week, the minimum frequency recommended. Exercises programmed for the aerobic exercise are treadmill, cycle-ergometer and elliptical ergometer in aerobic training part and weight bearing and guided pneumatic machines (involved major upper and lower body muscle group) in resistance training. Training load variation. We propose a gradual progression to control the exercise dose Training periodization divided in two phases of 5 weeks each one, starting with a familiarization phase (2 weeks). Training sessions. Sessions start with a dynamic standardized warm up, which include several muscle activation exercises. Aerobic sessions include compensatory exercises. Training session will be ended with a cooling-down protocol | Other: PAR<br> <br> |
| Experimental: HIIT group.<br>The volume in HIIT 40-65 min/week at high intensity. Intensity. Two different protocols: HIIT with long intervals (Type A session), which intensity will be >95% VO2max and HIIT with short intervals (Type B session), >120% VO2max. Training frequency two times/week. Type of exercise. Type A session are walking in treadmill with personalized slopes. Eight weight-bearing exercises in circuit form, type B session. Training load variation. Gradual progression to control the exercise dose. Training periodization divided in: familiarization phase, phase I, phase II. Training sessions. Type A: 5 minutes in treadmill at 60% VO2max. After warm-up, participants complete sets corresponding to each training session following the corresponding characteristics. Type B: eight weight-bearing exercises (in circuit form) two times/set with an active rest (walking at 60%VO2max) as many times at as defined. Training session will be ended with a cooling-down protocol | Other: HIIT<br> <br> |
| Experimental: WB-EMS group.<br>WB-EMS training program will be the same than HIIT intervention related to volume, intensity, frequency, type of exercise, training load variation, training periodization and training session. However, electrical impulse will be included in order to assess if WB-EMS training will produce an added effect compared to HIIT. Electrical parameters: We will apply a frequency of 15-33 Hz in type A session. And, we will apply a frequency of 35-75 Hz in type B session. Intensity will be 80-100 mA. Impulse Width adjusted in relation to body segment: thigh zone (400μsec), glute zone (350μsec), abdominal zone (300μsec), dorsal zone (250μsec), cervical (200μsec), chest zone (200μsec) and arm zone (200μsec). Duty cycle. We have programmed a duty cycle of 50-67% in type B session, but duty cycle in type A session will be 99%. RPE impulse: the impulse intensity was individually adapted to generate similar values of rate of perceived exertion (RPE) in Borg CR-10 Scale 5 of 9 | Other: WB-EMS<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| α-Klotho protein | Plasma Klotho concentrations will be measured by ELISA using a soluble α-Klotho ELISA assay kit. | Baseline and through study completion, an average of 12 weeks. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Physical fitness: cardiorespiratory fitness | Cardiorespiratory fitness measure through a maximum treadmill test (VO2max.). | Baseline and through study completion, an average of 12 weeks. | 
| Physical fitness: muscular strength. | Muscle strength measure through: Isokinetic strength, Handgrip strength and Core resistance stability. | Baseline and post-intervention.Baseline and through study completion, an average of 12 weeks. | 
| Body composition. | Measure by DXA. | Baseline and through study completion, an average of 12 weeks. | 
| Resting energy expenditure. | Evaluated by indirect calorimetry with gas analyzer breath by breath. | Baseline and through study completion, an average of 12 weeks. | 
| Hearth Rate Variability (HRV). | Measure by Polar RS800CX. | Baseline and through study completion, an average of 12 weeks. | 
| Biochemical profile. | General biochemical profile in blood samples | Baseline and through study completion, an average of 12 weeks. | 
| Physical activity. | The amount of physical activity will be measured by accelerometer. | Baseline and through study completion, an average of 12 weeks. | 
| Reaction time. | Measure by Vienna System. | Baseline and through study completion, an average of 12 weeks. | 
| Cognitive test. | Auditory memory tests | Baseline and through study completion, an average of 12 weeks. | 
| Dietary assessment. | Measure by 24h recall and Food Frecuency Questionnaire. | Baseline and post-Baseline and through study completion, an average of 12 weeks.. | 
| Anthopometric measures. | Measure by stadiometer and scale. | Baseline and post-Baseline and through study completion, an average of 12 weeks.. | 
| Sleep quality. | The quality of sleep will be measured by accelerometer. | Baseline and post-Baseline and through study completion, an average of 12 weeks.. | 
| Hormones profile | Hormones profile measure in blood samples. | Baseline and post-Baseline and through study completion, an average of 12 weeks.. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Physical fitness, Klotho, Training, HIIT, WB-EMS