Despite the wealth of epidemiological and experimental studies indicating the protective role of regular physical activity/exercise training against the sequels of aging and cardiovascular diseases, the molecular transducers of exercise/physical activity benefits are not fully identified but should be further investigated in more integrative and innovative approaches, as they bear the potential for transformative discoveries of novel therapeutic targets. As aging and cardiovascular diseases are associated with a chronic state of oxidative stress and inflammation mediated via complex and interconnected pathways, we will focus in this review on the antioxidant and anti-inflammatory actions of exercise, mainly exerted on adipose tissue, skeletal muscles, immune system, and cardiovascular system by modulating anti-inflammatory/proinflammatory cytokines profile, redox-sensitive transcription factors such as nuclear factor kappa B, activator protein-1, and peroxisome proliferator-activated receptor gamma coactivator 1-alpha, antioxidant and prooxidant enzymes, and repair proteins such as heat shock proteins, proteasome complex, oxoguanine DNA glycosylase, uracil DNA glycosylase, and telomerase. It is important to note that the effects of exercise vary depending on the type, intensity, frequency, and duration of exercise as well as on the individual’s characteristics; therefore, the development of personalized exercise programs is essential.
There is mounting evidence based on epidemiologic and experimental studies that physical activity and exercise training combat the sequels of aging. Physical activity is defined as any bodily movement coordinated by skeletal muscles, which increases energy expenditure over resting condition [
Age is a major risk factor for cardiovascular diseases (CVDs) [
The cardiovascular benefits of exercise have been frequently attributed to the reduction of many classical cardiovascular risk factors including blood lipids [
Aging is associated with oxidative stress that is mainly attributed to defective mitochondria, resulting from reduction in cytochrome C oxidase (complex IV) activity [
Reduced protein synthesis limits antioxidant defense mechanisms and repair capacity in aged individuals, which further contributes to the state of oxidative stress. The free radical theory of aging hypothesizes that oxidative stress damages macromolecules, including lipids, proteins, and nucleic acids, overwhelming cellular antioxidant defense and repair mechanisms, leading to progressive deleterious changes over time [
Aging is also accompanied with a state of chronic inflammation that is mainly attributed to sarcopenia and adiposity. Sarcopenia, defined as age-associated progressive loss of muscle mass and strength [
Sarcopenia can also lead to reduced physical activity and increased adiposity. Adiposity induces a state of low-grade but chronic inflammation through the release of a multitude of proinflammatory cytokines including tumor necrosis factor-alpha (TNF-
Cardiovascular diseases are also associated with high level of inflammation and oxidative stress [
Oxidative stress and inflammation share common and overlapping signaling pathways. By damaging macromolecules, ROS can initiate inflammation [
ROS overproduction activates redox-sensitive transcription factors including nuclear factor kappa B (NF-
There are also other proteins such as thioredoxin-interacting protein (TXNIP) linking oxidative stress and inflammation. Under resting conditions, TXNIP is bound to thioredoxin (TRX) via a disulphide bound, keeping it in an inactive form. Increased levels of ROS generation cause the dissociation of TXNIP from TRX, leaving it free to scavenge ROS and allowing TXNIP to stimulate the inflammatory cytokine IL-1
In short, proinflammatory mediators such as TNF-
Oxidative stress and inflammation overlapping signaling pathways in aging. AP-1 = activator protein-1, COX-2 = cyclooxygenase-2, cPLA2 = cytosolic phospholipase A2, ERKs = extracellular signal regulated kinases, ICAM-1 = intercellular adhesion molecule-1, IL-1 = interleukin-1, IL-8 = interleukin-8, iNOS = inducible nitric oxide synthase, JNKs = c-jun N-terminal kinases, LPO = lipoxygenase, MAPK p38 = mitogen activated protein kinase p38, PI3K = phosphatidylinositol-4,5-bisphosphate 3-kinase, MMP-9 = matrix metalloproteinase-9, MPO = myeloperoxidase, NF-
Not surprisingly, ROS can also induce proteins such as heat shock proteins (HSPs), HSP70 in particular [
Exercise and regular physical activity counteract the deleterious effects of aging, not only by combating sarcopenia, obesity, and mitochondrial dysfunction, the major triggers of oxidative stress and inflammation in aging, but also by exerting additional antioxidant and anti-inflammatory actions as illustrated in Figure
Modulation of oxidative stress and inflammation in aging by exercise.
Adipose tissue, particularly visceral fat depots, and the macrophages trapped within fat depots are able to release proinflammatory cytokines such as IL-6 and TNF-
Physical activity/exercise increases nutritive blood supply to and removes waste from skeletal muscles, while also upregulating the expression of the anabolic myokine IL-15 [
Physical activity/exercise also induces the release of several myokines from skeletal muscle such as IL-6 [
Heat shock proteins (HSPs) are also generated in skeletal muscles in response to physical activity/exercise; they exert vital anti-inflammatory action as will be explained later [
Exercise mitigates mitochondrial aging and interrupts the vicious cycle of oxidative damage by stimulating mitochondrial biogenesis [
Acute bouts of exercise cause transient damage to contracting skeletal muscles, triggering an inflammatory response that increases the levels of proinflammatory cytokines and acute-phase reactants in the blood [
Effect of physical activity/exercise on inflammatory mediators in the elderly.
Study | Mediator | Subjects | Tissue | Physical activity/exercise | Effect of physical activity/exercise | Reference |
---|---|---|---|---|---|---|
Observational | TNF- |
≥65 years |
Plasma | Self-reported physical activity | Inverse association between log TNF- |
[ |
65–80 years |
Serum | Regular exercise | Lower percentage in the physically active subgroup | [ | ||
CRP | ≥65 years |
Blood | Self-reported physical activity | Inverse association between physical activity and CRP | [ | |
Men, 58 years |
Blood | Self-reported leisure time physical activity | Inverse association between physical activity and CRP | [ | ||
70 to 79 years |
Blood | Self-reported physical activity | Inverse association between CRP and physical activity | [ | ||
70 to 79 years |
Blood | Previous week exercise and physical activities | Inverse association between physical activity and CRP | [ | ||
60 to 79 years |
Plasma | Self-reported physical activity | Inverse association between CRP and physical activity | [ | ||
70 to 79 years |
Plasma | Physical function measures included handgrip strength, signature time, chair stands, and 6-minute walk time | Inverse association between CRP and higher walking speed and grip strength | [ | ||
≥65 years |
Plasma | Self-reported physical activity | Inverse association between and log CRP and physical activity | [ | ||
65–80 years |
Serum | Regular exercise | Lower level in the physically active subgroup | [ | ||
50 to 70 years |
Plasma | Self-reported physical activity | Inverse association between CRP and physical activity | [ | ||
IL-6 | Men, |
Serum | Self-reported physical activity | Lower levels of IL-6 in the physically active group | [ | |
70 to 79 years |
Blood | Previous week exercise and physical activities | Lower level associated with higher level of physical activity | [ | ||
70 to 79 years |
Blood | Self-reported physical activities | Inverse association between IL-6 and physical activity | [ | ||
≥65 years |
Plasma | Self-reported physical activity | Inverse association between log IL-6 and physical activity | [ | ||
70 to 79 years |
Plasma | Physical function measures included handgrip strength, signature time, chair stands, and 6-minute walk time | Inverse association between IL-6 and higher walking speed | [ | ||
IL-10 | Men, |
Serum | Self-reported physical activity | Higher levels of IL-10 in the physically active group | [ | |
CD14+CD16+ | 65–80 years |
Serum | Regular exercise | Lower percentage in the physically active subgroup | [ | |
Adiponectin | 50 to 70 years |
Plasma | Self-reported physical activity | Direct association between adiponectin and physical activity | [ | |
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Interventional | TNF- |
≥64 years |
Blood | Aerobic or flexibility/strength exercise for 10 months | Reduced level by aerobic and strength exercise | [ |
Men, 67 ± 8 years with congestive heart failure |
Plasma | Exercise training for 3 months | Level reduced after training | [ | ||
81 ± 1 years |
Skeletal muscle | Exercise training for 3 months | Reduced mRNA and protein levels after training | [ | ||
65–80 years, |
Blood | 3 days/week endurance and resistance exercise training for 12 weeks | Reduced level compared with pretraining values | [ | ||
Postmenopausal women, 65–80 years |
Blood | Regular exercise for previous 6 months | No change in protein or mRNA | [ | ||
65–80 years |
Serum | Progressive resistance strength training for 12 weeks | No change | [ | ||
sTNF-R1 | Overweight/obese sedentary with knee osteoarthritis ≥60 years |
Serum | Combined weight training and walking for 1 h, 3 times/week for 18 months | No change | [ | |
CRP | Type 2 diabetic patients, |
Serum | Strength training for 16 weeks | Reduced level after training | [ | |
>64 years |
Blood | Aerobic or flexibility/strength exercise for 10 months | Reduced level by aerobic but not strength exercise | [ | ||
Postmenopausal overweight or obese, sedentary women, |
Serum | Moderate-intensity aerobic exercise for 12 months | Level reduced after training | [ | ||
Women with the metabolic syndrome, |
Blood | Four sessions of high-intensity aerobic and resistance exercise per week for 12 months | Level reduced after training | [ | ||
Patients with CHD, 66.7 ± 11 years |
Blood | Cardiac rehabilitation and exercise training for 3 months | Level reduced after training | [ | ||
60 to 85 years |
Serum | Exercise training for 6 months | No change | [ | ||
Overweight/obese sedentary with knee osteoarthritis ≥60 years |
Serum | Combined weight training and walking for 1 h, 3 times/week for 18 months | No change | [ | ||
Postmenopausal breast cancer survivors, |
Serum | Cycling 3 times/week for 15 weeks | No change | [ | ||
IL-6 | >64 years |
Blood | Aerobic or flexibility/strength exercise for 10 months | Reduced level by aerobic but not strength exercise | [ | |
70–89 years |
Plasma | Moderate-intensity combination of aerobic, strength, balance, and flexibility exercises for 12 months | Reduced IL-6 level but not CRP | [ | ||
Young (20–30 years) and aged (66–76 years) |
Blood | Endurance (20 min) and resistance exercise 3 days/week for 12 weeks | Stimulated level was reduced in young and old subjects | [ | ||
Postmenopausal women, 65–80 years |
Blood | Regular exercise for 6 months | No change in protein or mRNA | [ | ||
Overweight/obese sedentary with knee osteoarthritis ≥60 years |
Serum | Combined weight training and walking for 1 h, 3 times/week for 18 months | No change | [ | ||
65–80 years |
Serum | Progressive resistance strength training for 12 weeks | No change | [ | ||
IL-1 |
65–80 years |
Serum | Progressive resistance strength training for 12 weeks | No change | [ | |
IL-18 | >64 years |
Blood | Aerobic or flexibility/strength exercise for 10 months | Reduced level by aerobic but not strength exercise | [ | |
TLR4 | Postmenopausal women, 65–80 years | Blood | Regular exercise for 6 months | Lower level in trained versus untrained | [ | |
Young (20–30 years) and aged (66–76 years) |
CD14+ cell | Endurance (20 min) and resistance exercise 3 days/week for 12 weeks | Level reduced in young and old subjects | [ | ||
CD14+CD16+ | 65–80 years sedentary |
Blood | Endurance and resistance exercise training for 12 weeks (3 days/week) | Reduced level compared with pretraining values | [ | |
Adiponectin | Type 2 diabetic patients >55 years |
Serum | Strength training for 16 weeks | Increased level after training | [ |
It is worth noting that some interventional and randomized controlled trials studies did not detect a significant effect of regular exercise on systemic inflammatory biomarkers in adults [
On the other hand, the effects of resistance exercise on inflammatory mediators are mostly negative [
The signaling pathways underlying the anti-inflammatory effects of exercise are complex and not completely understood. In addition to the effects of exercise on adipose tissue, skeletal muscles, and mitochondrial biogenesis mentioned above, exercise exerts additional anti-inflammatory actions on the immune system, repair mechanisms, and vasculature.
Exercise also stimulates the sympathetic nervous system and the hypothalamic-pituitary-adrenal axis to increase serum glucocorticoid levels [
Effects of exercise training on HSPs in humans and experimental animals.
HSP | Species | Tissue | Physical activity/exercise mode | Effect of physical activity/exercise | References | |
---|---|---|---|---|---|---|
HSP72 | Human | Men, |
Plasma | Semirecumbent cycling for 120 min | Levels increased after exercise | [ |
Men and women, |
Serum | Acute bout of treadmill running for 60 min | Protein expression increased during and after exercise | [ | ||
Men and women, |
Skeletal muscle | Acute bout of treadmill running for 60 min | mRNA level increased after exercise | [ | ||
Rats | Young (3 months) and aged (30 months) | Skeletal muscle | 4.5 weeks of resistance exercise | Protein expression increased in young and old rats | [ | |
Adult females | Heart | 1 or 3 consecutive days for 100 min at a speed of 20 m/min | Increased expression | [ | ||
Adult males | Heart | Treadmill running for 1 or 3 days | Increased levels after 3 but not 1 day | [ | ||
Adult males | Heart | 24-week but not 12-week treadmill training | Increased expression | [ | ||
Females, |
Heart | Endurance exercise for 10 weeks | Increased expression | [ | ||
Females, |
Ventricle | 3–5 consecutive days of treadmill exercise [60 min/day at 60–70% maximal O2 uptake] | Increased levels | [ | ||
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HSP70 | Human | Male athletes, |
Leukocytes | Half marathon run | Protein expression increased | [ |
Men and women, |
Skeletal muscle | 30 min on a treadmill | mRNA level but not protein level increased at 4 min, 30 min, and 3 h after exercise | [ | ||
Women, |
Skeletal muscles | Acute bout of eccentric contractions | Protein expression increased after exercise | [ | ||
Rats | Aged 24 months old | Hearts | Treadmill training for 30 m/min, 45 min/day, 5 days/week for 6 weeks | Expression increased | [ | |
Young (6 months) and aged 27 months | Left ventricle | Treadmill for 60 min/day, 5 days/week for a total of 12 weeks | Protein increased in the young group compared with sedentary control | [ | ||
Males, young (4 months) and aged (21 months) | Heart | Acute exercise for 60 min at 70–75% of maximum oxygen consumption | Expression increased in young and old rats | [ | ||
Males, |
Heart | Treadmill for 3 days/week for 14 weeks | Increased protein level | [ | ||
Spontaneously hypertensive |
Aorta | Voluntary wheel running for 5 weeks | Reduced gene expression | [ | ||
Males and females, |
Skeletal muscle | Acute treadmill running for 30 min | Protein and mRNA expression increased in males but not females | [ | ||
Mice | Males |
Cardiac ventricles | Swimming training for 14 weeks | No change | [ | |
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HSP60 | Human | Male athletes, |
Leukocytes | Half marathon run | Expression increased | [ |
Rats | Males, |
Heart | Treadmill for 3 days/week for 14 weeks | Decreased mRNA | [ | |
Spontaneously hypertensive |
Aorta | Voluntary wheel running for 5 weeks | Reduced gene expression | [ | ||
Mice | Males, |
Ventricles | Swimming training for 14 weeks | Increased level | [ | |
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HSP32 | Rats | Females, |
Heart | Endurance exercise for 10 weeks | No change | [ |
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HSP27 | Human | Male athletes, |
Leukocytes | Half marathon run | Expression increased | [ |
Rats | Males, aged (24 months) | Hearts | Treadmill training for 30 m/min, 45 min/day, 5 days/week for 6 weeks | Expression increased | [ | |
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HSP25 | Rats | Males, young (3 months) and aged (30 months) | Skeletal muscles | 4.5 weeks of resistance exercise | Protein expression increased in young and old rats | [ |
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HSC70 | Human | Male athletes, |
Leukocytes | Half marathon run | No change | [ |
Rats | Males, young (3 months) and aged (30 months) | Skeletal muscles | Resistance exercise for 4.5 weeks | No change in protein expression | [ |
Signaling pathways underlying the anti-inflammatory actions of exercise. HSPs = heat shock proteins, IL-1
Generation of ROS is transiently increased during exercise; however, the incidence of diseases associated with oxidative stress is reduced by regular exercise. Regular exercise attenuates oxidative damage in the brain [
Importantly, regular exercise ameliorates age-associated oxidative stress in the heart [
In elderly people, regular exercise reduced serum/plasma levels of myeloperoxidase, a marker of inflammation and oxidative stress [
As discussed above, exercise exerts prominent anti-inflammatory actions, thus suppresses major sources of ROS and RNS generation, and produces indirect antioxidant effects. Exercise also upregulates the antioxidant defense mechanisms and repair proteins in the body via redox-sensitive transcription factors, mainly NF-
The metabolic demands of skeletal muscles increase during exercise; the body responds by increasing oxygen uptake and blood flow to the muscles and other body organs. The increased metabolic rate results in greater ROS production in skeletal muscles [
Effects of exercise training on expression and activity of antioxidant and prooxidant enzymes.
Enzyme | Species | Tissue | Exercise mode | Effect of physical activity/exercise | Reference | |
---|---|---|---|---|---|---|
SOD | Human | Untrained males |
Erythrocytes | High-intensity endurance training for 12 weeks | Activity increased after training | [ |
Healthy young men and women |
Erythrocytes | 16 weeks of training then an acute bout of aerobic exercise for 30 min | Transient increase in activity after acute exercise | [ | ||
Athletes |
Erythrocyte | Marathon or sprint training | Higher activity in sprint-trained athletes and marathon runners | [ | ||
Winter swimmers |
Erythrocyte | Regular winter swimming | Higher activity in winter swimmers | [ | ||
Rats | Males, young and aged (17 months) | Lung, heart, and liver | Regular swimming exercise for 1 year | Increased activity in lung and heart of old rats relative to sedentary controls | [ | |
Males, young and aged | Heart | Treadmill endurance exercise for 2 months | Increased activity in young and aged rats | [ | ||
Male, young, adult, and aged | Skeletal muscles | Exercise training for 10 weeks | Increased activity in deep vastus lateralis muscle of young rats only | [ | ||
Males, 16-17 weeks | Heart and skeletal muscle | Sprint training on a treadmill for 6 weeks | Unchanged activity | [ | ||
Females, 4 months | Ventricles | Endurance exercise training for 10 weeks | Increased activity | [ | ||
Females, 17 weeks | Ventricles | High-intensity exercise treadmill for 10 weeks | Increased activity | [ | ||
Males, adults | Heart | Treadmill training for 12 or 24 weeks | Increased activity after 24 but not 12 weeks | [ | ||
Males, myocardial infarcted | Aorta | Treadmill training 5 times per week, 60 min/day for 11 weeks | Increased activity but not expression | [ | ||
Mice | Males, aged 29–32 months | Aorta | Voluntary wheel running for 10–14 weeks | Increased activity | [ | |
Males and females, aged 28, 52, and 78 weeks | Bain, heart, liver, and kidney | Long term moderate-intensity treadmill exercise | Increased activity in all tissues at 52 but not 78 weeks old | [ | ||
Females, 3 months | Kidney, heart, and skeletal muscle | Treadmill exercise for 8 weeks | Increased activity | [ | ||
Males |
Ventricles | Swimming training for 14 weeks | No change in activity | [ | ||
Microtus | Short-tailed field vole |
Skeletal muscle and heart | Voluntary running over 1 or 7 days | Reduced activity in the heart | [ | |
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SOD-1 | Human | Umbilical vein endothelial cells | Laminar fluid shear stress | mRNA and protein levels increased after 24 hours | [ | |
Endothelial progenitor cells | Shear stress | Increased mRNA expression and activity | [ | |||
Aortic endothelial cells | Fluid shear stress | Increased protein expression | [ | |||
Patients with congestive heart failure |
Skeletal muscle | 12 weeks of training | Increased gene expression | [ | ||
Rats | Young (3 months) and aged (30 months) | Skeletal muscles | 4.5 weeks of resistance exercise | Protein expression increased in young rats but decreased in old rats | [ | |
Males, young (3–5 months) and aged (24–27 months) | Skeletal muscles and heart | Exhausting treadmill running | Increased activity in skeletal muscles and heart of young rats and hearts of old rats | [ | ||
Males, aged 24 months | Hearts | Treadmill training 30 m/min, 45 min/day, 5 days/week for 6 weeks | Protein expression increased | [ | ||
Males, young (2 months) and old (22 months) | Soleus muscle feed arteries | Exercise training for 10–12 weeks | No change in protein expression | [ | ||
Females, |
Hippocampus | Treadmill training for 15 weeks | Protein expression increased | [ | ||
Females | Skeletal muscle | Acute bout of exhaustive treadmill exercise | Increased protein level but not mRNA or activity | [ | ||
Males, adults | Heart | Acute session of treadmill running for 25–30 min | No change | [ | ||
Females, adults | Ventricles | 20 weeks of training | Increased protein expression | [ | ||
Males, high caloric fed | Aorta and mesenteric artery | Running 60 min, 5 days/week for 12 weeks | Increased expression relative to sedentary controls | [ | ||
Mice | Aorta | Treadmill running 15 m/min, 30 min/day, 5 days/week for 3 weeks | No change in protein expression | [ | ||
Males, diabetic young | Aorta | Treadmill exercise for 10 weeks | Increased protein expression | [ | ||
Pigs | Females | Aortic endothelial cells | Chronic exercise training for 16–19 weeks | Protein and activity increased | [ | |
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SOD-2 | Human | Men |
Plasma | Swimming or running for 3 months then a bout of acute exercise | Protein level increased by acute exercise | [ |
Men 62 ± 3 years |
Vascular endothelial cells from the brachial artery | Habitual aerobic exercise | Higher protein expression than sedentary men | [ | ||
Rats | Males, 10-11 weeks | Cardiac mitochondria | Long term voluntary wheel running | Reduced activity | [ | |
Males, adults | Heart | Treadmill training for 12 or 24 weeks | Increased activity after 24 but not 12 weeks | [ | ||
Males, adults | Heart | Acute session of treadmill running for 25–30 min | Activity increased at 0.5 and 48 h, and protein content increased at 48 h after exercise | [ | ||
Females, |
Heart | 3–5 consecutive days of treadmill exercise [60 min/day at 60–70% maximal O2 uptake] | Increased activity | [ | ||
Females, 4 months | Ventricles | Treadmill exercise (60 min/day) at 25 degrees for 3 days | Increased activity | [ | ||
Females, adults | Ventricles | 20 weeks of training | Increased protein expression | [ | ||
Males subjected to IR | Ventricles | 3 consecutive days of intensive treadmill exercise 60 min/day, at 30 m/min | Increased activity of SOD-2 but not SOD-1 | [ | ||
Males, aged 24 months | Heart | Treadmill training 30 m/min, |
Protein expression increased | [ | ||
Males, young (4 months) and aged (21 months) | Heart | Acute exercise 60 min at 70–75% of maximum oxygen consumption | Activity increased in old rats | [ | ||
Young (6 months) and aged 27 months | Left ventricle | Treadmill for 60 min/day, 5 days/week for a total of 12 weeks | Protein expression and activity increased in the aged group compared with sedentary control | [ | ||
Females | Skeletal muscle | Treadmill running for 10 weeks | Increased activity and protein expression | [ | ||
Females | Skeletal muscles | Acute bout of exhaustive treadmill exercise | Increased mRNA level in deep vastus lateralis muscle. Increased protein level in superficial vastus lateralis | [ | ||
Male Zucker diabetic fatty rats (18 weeks) | Skeletal muscles | Swimming training for 6 weeks | Protein expression increased | [ | ||
Males, |
Plasma | Treadmill training 3 days/week for 14 weeks | Increased activity | [ | ||
Males, obese Zucker | Liver | Treadmill running at 20 m/min for 1 h/day, 7 days/week, for 8 weeks | mRNA and protein levels and activity increased | [ | ||
Male, young (3 months) and aged (23 months) | Aorta | Treadmill training for 12 weeks | Increased protein expression in aged rats | [ | ||
Mice | Male, diabetic and young | Heart | Motorized exercise-wheel for 1 h/day, 5 days/week for 8 weeks | Increased protein expression | [ | |
Male, diabetic and young | Aorta | Motorized exercise-wheel for 1 h/day, 5 days/week for 8 weeks | Increased protein expression | [ | ||
Pigs | Females | Aortic endothelial cells | Chronic exercise training for 16–19 weeks | No change in protein levels | [ | |
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SOD-3 | Human | Men 62 ± 3 years |
Vascular endothelial cells from the brachial artery | Habitual aerobic exercise | Higher activity than sedentary men | [ |
Men |
Plasma | Swimming or running for 3 months then a bout of acute exercise | Reduced protein level after endurance training but increased by acute exercise | [ | ||
Rats | Males, young (2 months) and old (22 months) | Soleus muscle feed arteries | Exercise training for 10–12 weeks | Increased protein expression in old rats | [ | |
Mice | Aorta | Treadmill running 15 m/min, 30 min/day, 5 days/ week for 3 weeks | Increased protein expression | [ | ||
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CAT | Human | Athletes |
Erythrocytes | Marathon or sprint training | Lower activity than controls in sprint-trained athletes | [ |
Winter swimmers |
Erythrocytes | Regular winter swimming | Higher activity in winter swimmers | [ | ||
Rats | Males, young and aged (17 months) | Lung, heart and liver | Regular swimming exercise for 1 year | Increased activity in liver of old rats relative to sedentary controls | [ | |
Aged | Brain, liver, lung, muscle, and testes | Regular exercise | Increased activity in all tissues | [ | ||
Males, young (4 months) and aged (21 months) | Heart | Acute exercise 60 min at 70–75% of maximum oxygen consumption | Activity increased in young and old rats | [ | ||
Male, young and aged | Heart | Treadmill exercise for 2 months | Increased activity in young and aged rats | [ | ||
Males, young (9 months) and aged (20 months) | Liver | Regular exercise | Increased activity | [ | ||
Male, young (8 months) and aged (22 months) | Brain | Swimming 30 min/day, 5 days/week for 12 weeks | Increased activity in hippocampus in young and old rats | [ | ||
Male, young (8 weeks), adult (12 months), and old (24 months) | Skeletal muscles | Exercise training for 10 weeks | Decreased activity in soleus muscle of adult and old rats | [ | ||
Males (4 months) | Cardiac mitochondria | Treadmill for 16 weeks (5 days/week, 60 min/day, 25 m/min) | Increased activity | [ | ||
Males, adults | Heart | Treadmill training for 12 or 24 weeks | Reduced activity after 24 but not 12 weeks | [ | ||
Females, 4 months | Ventricles | Endurance exercise training for 10 weeks | No change in activity | [ | ||
Males subjected to IR | Ventricles | 3 consecutive days of intensive treadmill exercise 60 min/day, at 30 m/min | Increased activity | [ | ||
Females | Skeletal muscle | Treadmill running for 10 weeks | Increased activity in deep vastus lateralis muscle | [ | ||
Male, normotensive and hypertensive (11-12 weeks) | Liver, kidney, skeletal muscles, and heart | Treadmill running for 10 weeks | Reduced activity in all tissues in hypertensive and normotensive rats | [ | ||
Mice | Males and females, aged 28, 52, and 78 weeks | Brain, heart, liver, and kidney | Long term moderate-intensity treadmill exercise | Increased activity in all issues at 52- but not 78-week-old mice | [ | |
Females, 3 months | Liver, heart, skeletal muscle, and salivary gland | Treadmill for a total of 8 weeks | Increased activity | [ | ||
Pigs | Females | Aortic endothelial cells | Exercise training for 16–19 weeks | No change in protein level | [ | |
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GPX | Human | Untrained males |
Erythrocytes | High-intensity endurance training for 12 weeks | Increased activity after training | [ |
Healthy young |
Blood | 16 weeks of training then an acute bout of aerobic exercise for 30 min | Activity increased after regular training and transiently reduced following acute exercise | [ | ||
Exercising and sedentary, young (21–38 years) and old (65–75 years) |
Erythrocyte | Regular exercise | Higher activity in the exercising elderly compared to the sedentary elderly | [ | ||
Athletes |
Erythrocyte | Marathon or sprint training | Higher activity in sprint-trained athletes | [ | ||
Patients with CHF |
Skeletal muscle | Moderate-intensity semirecumbent bicycle training for 12 weeks | Increased gene expression | [ | ||
Rats | Males, young and aged (17 months) | Lung, heart, and liver | Regular swimming for 1 year | Activity increased in liver, lung, and heart of old rats relative to sedentary controls | [ | |
Aged | Brain liver, lung, muscle, and testes | Regular exercise | Increased activity in brain, liver, lung, and testes | [ | ||
Male, young (8 months) and aged (22 months) | Brain | Swimming 30 min/day, 5 days/week for 12 weeks | Increased activity in hippocampus in young and aged | [ | ||
Females, |
Hippocampus | Treadmill for a period of 15 weeks | Protein expression increased | [ | ||
Females |
Skeletal muscles | Treadmill training (60 min, 5 days/week for 10 weeks) | Increased activity | [ | ||
Male, young (8 weeks), adult (12 months), and old (24 months) | Skeletal muscles | Exercise training for 10 weeks | Increased activity in deep vastus lateralis muscle of young rats only | [ | ||
Young (5 months) and aged (27.5 months) | Skeletal muscles | Treadmill training for 10 weeks | Increased activity in deep vastus lateralis muscle of old rats only | [ | ||
Males, young (9 months) and aged (20 months) | liver | Regular exercise | Increased activity | [ | ||
Males, obese Zucker | Liver | Treadmill running at 20 m/min for 1 h/day, 7 days/week for 8 weeks | mRNA and protein levels and activity increased | [ | ||
Males, young | Liver, heart, and muscle | Swim training for 10 weeks | Increased activity in all tissues | [ | ||
Females, 4 months | Ventricles | Endurance training for 10 weeks | No change in activity | [ | ||
Males, adult | Heart | Treadmill training for 12 or 24 weeks | No change in activity | [ | ||
Males, 16-17 weeks | Skeletal muscle and heart | Sprint training on a treadmill for 6 weeks | Increased activity in heart and some skeletal muscle fibres | [ | ||
Females | Skeletal muscle | Treadmill running for 10 weeks | Increased activity in deep vastus lateralis muscle | [ | ||
Male, normotensive and hypertensive (11-12 weeks) | Liver, kidney, skeletal muscles, and heart | Treadmill running for 10 weeks | Reduced activity in all tissues in hypertensive and normotensive rats | [ | ||
Mice | Females, 3 months | Liver, kidney, and heart | Treadmill for a total of 8 weeks | Increased activity | [ | |
Males |
Ventricles | Swimming training for 14 weeks | No change in activity | [ | ||
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GSR | Human | Healthy young |
Plasma | 16 weeks of training then an acute bout of aerobic exercise for 30 min | Activity increased after regular training | [ |
Mice | Males |
Ventricles | Swimming training for 14 weeks | No change in activity | [ | |
Rats | Males, adults | Heart | Treadmill training for 12 or 24 weeks | No change in activity | [ | |
Males, 16-17 weeks | Skeletal muscle and heart | Sprint training on a treadmill for 6 weeks | Increased activity in heart and some skeletal muscle fibres | [ | ||
Males, young | Liver, heart, and muscle | Swim training for 10 weeks | Increased activity in all tissues | [ | ||
Aged | Brain liver, lung, muscle, and testes | Regular exercise | Increased activity in testes | [ | ||
Males, young (8 weeks), adult (12 months), and old (24 months) | Skeletal muscles | Exercise training for 10 weeks | Activity increased in deep vastus lateralis muscle of young rats and decreased in soleus muscle of adult rats only | [ | ||
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GST | Mice | Females, 3 months | Liver and salivary gland | Treadmill for a total of 8 weeks | Increased activity | [ |
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NAD(P)H oxidase | Human | Patients with symptomatic coronary artery disease |
Internal mammary artery | Aerobic training for 4 weeks | Reduced protein and gene expression and activity | [ |
Men, 62 ± 3 years, physically active |
Vascular endothelial cells from the brachial artery | Habitual aerobic exercise | Lower level of p47(phox) compared with sedentary men | [ | ||
Rats | Males, young and myocardial infarcted | Aorta | Treadmill training 5 times per week, 60 min/day for 11 weeks | Reduced activity | [ | |
Male, adult (6 months) and aged (24 months) | Aorta | Swim training (60 min/day, 5 days/week for 10 weeks) | Decreased expression of gp91(phox) | [ | ||
Pigs | Females | Aortic endothelial cells | Chronic exercise training for 16–19 weeks | Reduced protein expression of p67(phox) | [ | |
Mice | Young (6–8 months) and aged (29–32 months) | Aorta | Voluntary wheel running for 10–14 weeks | Reduced expression and activity | [ | |
Males, diabetic and young | Aorta | Treadmill exercise for 10 weeks | Decreased protein expression of gp91(phox) | [ |
Athletes’ erythrocytes had higher SOD activity compared with untrained individuals [
Exercise-induced adaptation of antioxidant and prooxidant enzymes is highly isoform [
Signaling pathways underlying the antioxidant actions of exercise. AMPK = AMP-activated protein kinase, AP-1 = activator protein-1, CREB = cAMP-response-element binding, HSPs = heat shock proteins, GPX = glutathione peroxidase, MAPKs = mitogen activated protein kinases, NF-
Exercise training confers a myriad of physiological benefits in aging and cardiovascular diseases through its antioxidant and anti-inflammatory actions. The inflammatory actions of exercise are mainly exerted on adipose tissue (by reducing its mass and inflammatory environment), on the immune system (by shifting immune cells towards the less inflammatory phenotype, modulating the cytokines profile, and stimulating glucocorticoids), on skeletal muscles (by stimulating mitochondrial biogenesis, upregulating the anabolic myokine IL-15, anti-inflammatory cytokines, and repair proteins, improving muscle mass and strength, and reducing proinflammatory cytokines), and on the vasculature (by increasing laminar shear stress). It is likely that regular exercise exerts the most substantial anti-inflammatory effects in patients having high baseline inflammatory biomarkers, particularly when associated with visceral fat loss.
Exercise exerts antioxidant effects by suppressing inflammatory pathways and therefore inhibiting prominent sources of RONS generation. Importantly, exercise also activates redox-sensitive transcription factors, mainly NF-
The authors declare that there is no conflict of interests regarding the publication of this paper.