Effect of Physical Activity/Exercise on Oxidative Stress and Inflammation in Muscle and Vascular Aging

Abstract

Functional status is considered the main determinant of healthy aging. Impairment in skeletal muscle and the cardiovascular system, two interrelated systems, results in compromised functional status in aging. Increased oxidative stress and inflammation in older subjects constitute the background for skeletal muscle and cardiovascular system alterations. Aged skeletal muscle mass and strength impairment is related to anabolic resistance, mitochondrial dysfunction, increased oxidative stress and inflammation as well as a reduced antioxidant response and myokine profile. Arterial stiffness and endothelial function stand out as the main cardiovascular alterations related to aging, where increased systemic and vascular oxidative stress and inflammation play a key role. Physical activity and exercise training arise as modifiable determinants of functional outcomes in older persons. Exercise enhances antioxidant response, decreases age-related oxidative stress and pro-inflammatory signals, and promotes the activation of anabolic and mitochondrial biogenesis pathways in skeletal muscle. Additionally, exercise improves endothelial function and arterial stiffness by reducing inflammatory and oxidative damage signaling in vascular tissue together with an increase in antioxidant enzymes and nitric oxide availability, globally promoting functional performance and healthy aging. This review focuses on the role of oxidative stress and inflammation in aged musculoskeletal and vascular systems and how physical activity/exercise influences functional status in the elderly.

Keywords: aging; cardiovascular system; exercise; inflammation; muscle; oxidative stress; physical activity.

Figure 1

Positive effects of physical activity/exercise on aging-related functional outcomes are evidenced at different levels.

Figure 2

Exercise modulates different signaling pathways affected by aging in skeletal muscle. Aging is associated with muscle mass loss and a reduction in muscle strength resulting from inefficient pathway of anabolic resistance (characterized by decreased insulin-like growth factor (IGF-1) and proteasome dysregulation and mitochondrial dysfunction, specifically reduced expression of factor peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) and transcription factor A mitochondrial (TFAM). In addition, increased oxidative stress resulting from the imbalance of increased reactive oxygen species, ROS, and reduced nuclear erythroid-2 like factor-2 (Nrf2), increased chronic low-grade inflammation (increased proinflammatory cytokines and decreased anti-inflammatory cytokines), jointly with myokine dysregulation play a key role in muscle alteration observed with aging. Exercising results in improved proteostasis regulation where protein synthesis increased while protein degradation is reduced. On the other hand, exercise increased mitochondrial biogenesis, reduced age-related oxidative damage, diminished chronic inflammation, and improved myokine profile, which consequently improves muscle structure and function.

Figure 3

Physical activity/exercise improves different mechanisms through which aging deteriorates vascular function. Endothelial dysfunction and arterial stiffness are two specific vascular phenotypes of vascular aging. The underlying mechanisms of vascular alteration associated with aging includes decreased mitochondrial function and increased expression of vascular NOX, both leading to increased ROS production and further reducing NO availability. Additionally, decreased antioxidant response mediated by Nrf2, increased MMP, reduced SOD activity, enhanced inflammatory mediators, NF- κB, and increased levels of the NO synthase endogenous inhibitor, ADMA, contribute to increasing the risk of developing cardiovascular disease and age-related frailty. Exercise/physical activity improves endothelial function and arterial stiffness through reducing inflammatory and oxidative damage signaling in vascular tissue together with an increase in antioxidant enzymes and NO availability. These improvements prevent or delay the onset of frailty and decrease clinical cardiovascular disease. ADMA: asymmetric dimethylarginine, CVD: cardiovascular disease, NF-κB: nuclear transcription factor-kappa B, NO: nitric oxide, NOX: nicotinamide adenine dinucleotide oxidase, Nrf2: nuclear erythroid-2 like factor-2, ROS: reactive oxygen species, SOD: superoxide dismutase.

Figure 4

Physical exercise types as promoters of healthy aging. Different modalities of physical exercise (strength/power, aerobic, flexibility, and balance) exert benefits on multiple clinical variables through improving muscular and vascular functions. The expression of these benefits is associated with a healthy aging phenotype.