Exercise Modulates Oxidative Stress and Inflammation in Aging and Cardiovascular Diseases

Abstract

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.

Figure 1

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-κB = nuclear factor kappa B, PGE₂ = prostaglandin E₂, PKC = protein kinase C, RONS = reactive oxygen nitrogen species, Sph1P = sphingosine-1-phosphate, TNF-α = tumor necrosis factor-alpha, VCAM-1 = vascular cell adhesion molecule-1, and XO = xanthine oxidase.

Figure 2

Modulation of oxidative stress and inflammation in aging by exercise.

Figure 3

Signaling pathways underlying the anti-inflammatory actions of exercise. HSPs = heat shock proteins, IL-1α = interleukin-1-alpha, IL-1ra = interleukin-1 receptor antagonist, IL-1β = interleukin-1 beta, IL-6 = interleukin-6, IL-8 = interleukin-8, IL-10 = interleukin-10, IL-15 = interlukin-15, INFγ = interferon gamma, M1 = macrophage phenotype 1, M2 = macrophage phenotype 2, ROS = reactive oxygen species, sTNFR2 = soluble TNF-α receptor 2, sIL-6R = soluble IL-6 receptor, TLR4 = toll-like receptor-4, TGFβ1 = transforming growth factor beta 1, TNF-α = tumor necrosis factor-alpha, Th1 = Type 1 helper T cell, and Th2 = Type 2 helper T cell.

Figure 4

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-κB = nuclear factor kappa B, OGG1 = oxoguanine DNA glycosylase, PGC-1α = peroxisome proliferator-activated receptor gamma, coactivator 1-alpha, SOD = superoxide dismutase, ROS = reactive oxygen species, TrxR1 = thioredoxin reductase 1, and UDG = uracil DNA glycosylase.