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via Clock and Bmal1 , important regulators of cellular senescence in vivo , a state in which the balance between ROS and antioxidants is disturbed (Yuan et al., 2017

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Antioxidants also indirectly reduce oxidative damage by preventing the expression of enzymes responsible for generating ROS, such as NAD(P)H oxidase and xanthine oxidase, or by promoting the activity or expression of free radical scavengers

When it's chronically overloadedfrom running, standing for long periods, or even improper footwearit develops microscopic tears