Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and exercise

Chronic metabolic health diseases are increasing worldwide placing strain on healthcare systems and importantly, impacting individuals’ quality of life. It is well established that many chronic diseases are associated with inflammation and oxidative stress. Exercise is a known strategy to manage and treat inflammation in animals and humans. Understanding the mechanisms which cause acute and chronic changes to systems via various exercise protocols may provide insights into how we can better clinically manage patients with inflammatory and oxidative stress associated diseases. Nrf2 is a basic leucine transcription factor which regulates the expression of antioxidant proteins to protect against damage caused by electrophilic or oxidative stress. The aim of this narrative review is to provide an overview of the literature which has investigated the relationship between acute and chronic exercise training and Nrf2 protein, mRNA and Nrf2-ARE binding activity. This narrative review presents analysis of twenty-nine articles presenting studies using animals and humans. Findings from animal models suggest that exercise increases all molecular aspects of the Nrf2-ARE pathway in all tissues studied. It was noted that there seems to be an age-related decline in Nrf2 protein upregulation with exercise training. In humans, however, there is a lack of evidence to support this claim. Images adapted from [1] and [2]. 1. Qin J-J, Cheng X-D, Zhang J et al. Dual roles and therapeutic potential of Keap1-Nrf2 pathway in pancreatic cancer: a systematic review. Cell Communication and Signaling. 2019 2019/09/11;17(1):121. https://doi.org/10.1186/s12964-019-0435-2. 2. Micah Lawrence. Running man [Icon]. https://thenounproject.com/micmarlawrence/: The Noun Project; 2013 [Display omitted] •There is evidence to suggest that exercise increases the Nrf2-ARE pathway in animal models.•Human research into the effect of exercise on Nrf2 is poor.•Nrf2 protein upregulation from exercise stress seems to decline with age.•Low-intensity exercise may not provide enough stimulus to increase Nrf2 protein.