**6. Mechanisms**

Uptodate, there are many mechanisms explaining the beneficial effects of exercise therapy. These include enhancing antioxidant defenses. Very promising are mainly small non‐coding microRNAs (miRNAs).

#### **6.1. Mechanisms that enhance antioxidant defenses**

An important mechanism that contributes to many disease is oxidative stress [8], although exhaustive and/or unaccustomed exercise in both aerobic and anaerobic exercise can generate excessive reactive oxygen species (ROS) according to mitochondrial enzymes, NADPH oxidases, and xanthine oxidases. This results in oxidative stress‐related tissue damages and impaired muscle contractility. Moderate exposure to ROS is needed to induce adaptive responses of the body such as the activation of antioxidant defense mechanisms [9]. Regular exercise is well known to benefit health by enhancing antioxidant defenses in the body [10], thereby leading to a reduced generation of free radicals both at rest and in response to exercise stress. Therefore, exercise training‐induced antioxidant activity decreases risk of many diseases.

In the elderly, sarcopenia is characterized by structural, biochemical, molecular and functional muscle changes. An imbalance between anabolic and catabolic intracellular signaling pathways and an increase in oxidative stress both play important roles in muscle abnormalities.

Regular exercise is promoted as a therapeutic strategy for age‐associated endothelial dysfunction. However, sex was shown to affect the antioxidant response in the elderly. Improvements in endothelial function are found with endurance exercise in older men, but are reduced or absent in older women. This may be due to sex hormones modulating vascular adaptations to exercise training by influencing antioxidant defense systems, mitochondrial function, oxidative stress, and intracellular signaling [11].

#### **6.2. Mechanisms that decrease the risk of developing cancer**

In addition, exercise is known to be one of several lifestyle factors that lower the risk of cancer and is associated with lower relapse rates and better survival. The indirect effects included changes in vitamin D, weight reduction, sunlight exposure and improved mood. The direct effects included insulin‐like growth factor, epigenetic effects on gene expression and DNA repair, vasoactive intestinal peptide, and antioxidant pathways, heat shock proteins, testosterone, irisin, immunity, chronic inflammation and prostaglandins, energy metabolism and insulin resistance [12].

#### **6.3. Mechanisms that are responsible to cardioprotection**

Importantly, exercise protects cardiovascular system through the modulation of


Moreover, Wand Exercise which is Thai mode of exercise significantly reduced body mass, total fat mass, waist and hip circumferences and increased flexibility, functional capacity (determined by 6MWD), physical health dimension and vitality of mental health dimension of the QOL [14]. The results showed that Thai Wand Exercise training decreased obesity, improved physical health status, and vitality. Therefore, this easy and low impact exercise program is a good approach to reduce cardiovascular risks. Data on cardioprotective effects of low‐intensity exercise are controversial. This could be due to the fact that low‐ intensity exercise may not meet the recommended minimum threshold of exercise intensity form improving cardiorespiratory endurance [15]. However, our research group found that low‐intensity exercise improved aerobic capacity of overweight and normal weight sedentary young adults [16]. Exercise also mediated improvement in hyperglycemia‐induced cardiovascular dysfunction in patients with type 2 diabetes [10]. Exercise training also improved insulin resistance‐induced lipotoxicity, mediated protection against pro‐inflammatory cytokines and improved pro‐survival signaling cascade. An appropriate duration and intensity of exercise can decrease myocardial dysfunction through the improvement of maximum oxygen consumption (VO2max), left ventricular ejection fraction (LVEF), LV diastolic and systolic volumes, ventilatory threshold, cardiac output and diastolic function (E/A ratio) [13, 17–25].

#### **6.4. Mechanisms that improve respiratory function**

exercise is well known to benefit health by enhancing antioxidant defenses in the body [10], thereby leading to a reduced generation of free radicals both at rest and in response to exercise stress. Therefore, exercise training‐induced antioxidant activity decreases risk of many

In the elderly, sarcopenia is characterized by structural, biochemical, molecular and functional muscle changes. An imbalance between anabolic and catabolic intracellular signaling pathways and an increase in oxidative stress both play important roles in muscle abnormalities. Regular exercise is promoted as a therapeutic strategy for age‐associated endothelial dysfunction. However, sex was shown to affect the antioxidant response in the elderly. Improvements in endothelial function are found with endurance exercise in older men, but are reduced or absent in older women. This may be due to sex hormones modulating vascular adaptations to exercise training by influencing antioxidant defense systems, mitochondrial function, oxida-

In addition, exercise is known to be one of several lifestyle factors that lower the risk of cancer and is associated with lower relapse rates and better survival. The indirect effects included changes in vitamin D, weight reduction, sunlight exposure and improved mood. The direct effects included insulin‐like growth factor, epigenetic effects on gene expression and DNA repair, vasoactive intestinal peptide, and antioxidant pathways, heat shock proteins, testosterone, irisin, immunity, chronic inflammation and prostaglandins, energy metabolism and

**c)** systemic risk factors. Both moderate‐ and high‐intensity exercise training were shown to

Moreover, Wand Exercise which is Thai mode of exercise significantly reduced body mass, total fat mass, waist and hip circumferences and increased flexibility, functional capacity (determined by 6MWD), physical health dimension and vitality of mental health dimension of the QOL [14]. The results showed that Thai Wand Exercise training decreased obesity, improved physical health status, and vitality. Therefore, this easy and low impact exercise program is a good approach to reduce cardiovascular risks. Data on cardioprotective effects of low‐intensity exercise are controversial. This could be due to the fact that low‐ intensity exercise may not meet the recommended minimum threshold of exercise intensity form improving cardiorespiratory endurance [15]. However, our research group found that

diseases.

86 Clinical Physical Therapy

tive stress, and intracellular signaling [11].

insulin resistance [12].

**a)** cardiac performance directly,

**b)** endothelial and vascular functions,

**6.2. Mechanisms that decrease the risk of developing cancer**

**6.3. Mechanisms that are responsible to cardioprotection**

Importantly, exercise protects cardiovascular system through the modulation of

improve aerobic capacity of metabolic syndrome patients [13].

Exercise training has been shown to improve pulmonary function in patients with type 2 diabetes [26]. Exercise training improves exercise tolerance and health‐related quality of life in patients with very severe COPD [27]. RME training led to a significant increase in respiratory muscle endurance in children with CF [28]. In addition, pulmonary rehabilitation reduced expiratory flow limitation (EFL) in COPD patients [29].

#### **6.5. Mechanisms that treat orthopedic patients**

A systematic review revealed that short‐term Traditional Chinese exercise (TCE) was potentially beneficial in terms of reducing pain, improving physical function and alleviating stiffness for patient [30]. In individuals operated with total knee arthroplasty, the 12‐month progressive home exercise program starting 2 months after the operation comparing to usual care improved maximal gait velocity, cadence and stance time [31]. This may be due to exercise loading in the cartilage‐subchondral bone (SB) unit in attenuation of post‐traumatic osteoarthritis development [32].

#### **6.6. Mechanisms that mediate differential expression of microRNAs**

MicroRNA is a non‐coding RNA which is increasingly interesting from scientists in many fields including Physical therapist [33]. It has been shown to regulate many process in our body, for example, muscle‐specific miRs (miR‐1, miR‐133 and miR‐499), the vascular wall of the vascular smooth muscle cells miR‐222, EC miR‐126, and the pathophysiology of Diabetic heart disease.

Exercise training, both acute endurance and resistance in healthy male volunteers, was shown to enhance miR‐133 expression in the vastus lateralis muscles [34, 35]. Moreover, endurance exercise elevated circulating levels of miR‐133 in healthy individuals after either an acute bout of aerobic exercise, or endurance training [36, 37]. Marathon training also increased miR‐133 level which is appeared to be associated with improved VO2max [38]. Similarly, T2DM mice which did a 10‐week swimming exercise had increased miR‐133 expression in cardiac tissue. Their contractile function improved and matrix metallopeptidase‐9 (MMP‐9), an extracellular matrix regulator protein decreased [39]. Since miR‐133 is reported to be expressed and enriched in both cardiac and skeletal muscles [40], it is possible that miR‐133 is secreted from skeletal muscle into the circulation after a bout of exercise, which then travels to the cardiomyocytes to suppress fibrotic markers and reduce cardiac hypertrophy.

#### **6.7. Mechanisms that treat neurological patients**

In Parkinson's disease patients, aerobic exercise training [28] may be altering central nervous system pathways that regulate the physiologic or cognitive processes controlling olfaction [41]. In spinal cord injury patients, the exercise training has been considered to improve spinal cord function not only through enhancement, compensation, and replacement of the remaining function of nerve and muscle but also improve the function in different levels from end‐ effector organ such as skeletal muscle to cerebral cortex through reshaping skeletal muscle structure and muscle fiber type, regulating physiological and metabolic function of motor neurons in the spinal cord and remodeling function of the cerebral cortex [42].
