Transcription factor NRF2 as potential therapeutic target for preventing muscle wasting in aging chronic kidney disease patients

Increased muscle protein catabolism leading to muscle wasting is a prominent feature of the syndrome of protein-energy wasting (PEW) in patients with chronic kidney disease (CKD). PEW and muscle wasting are induced by factors such as inflammation, oxidative stress and metabolic acidosis that activate the ubiquitin–proteasome system, the main regulatory mechanism of skeletal muscle degradation. Whether deficiency of nuclear factor erythroid 2-related factor 2 (NRF2), which regulates expression of antioxidant proteins protecting against oxidative damage triggered by inflammation, may exacerbate PEW has yet to be examined in aging patients with CKD. This review focuses on the hypothesis that NRF2 is involved in the maintenance of muscle mass and explores whether sustained activation of NRF2 by non-pharmacological interventions using nutraceutical activators to improve redox homeostasis could be a plausible strategy to prevent skeletal muscle disorders, including muscle wasting, sarcopenia and frailty associated with PEW in aging CKD patients. GRAPHICAL ABSTRACT: [Image: see text]