Exosomal Nrf2: From anti-oxidant and anti-inflammation response to wound healing and tissue regeneration in aged-related diseases

Accumulation of oxidative stress in cells is an essential feature of cellular senescence and aging. This phenomenon is involved in different age-related diseases through dysregulation of homeostasis and impairing repair and regeneration (wound healing) capacity, which can suppress antioxidant responses such as the activity of antioxidant enzymes and damaged protein clearance system. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcription factor which regulates basal and inducible expression pattern of specific genes (antioxidants and detoxifications) through antioxidant element response (ARE) sites in the stress condition, specifically in chronic and age-related stresses. Nrf2 maintains cellular redox hemostasis and promotes rejuvenation. Exosomes are nanoscale vesicles that are released by various cells to actively regulate the complex cellular signaling networks. Exosomal-Nrf2 and exosomal-Nrf2-mediated products can modulate oxidative hemostasis in target cells to induce tissue repairing with therapeutic proposes, and regeneration capability. In this study, we summarized the role of exosomal-Nrf2 in different age-related diseases, including diabetic foot ulcers, atherosclerosis, chronic heart failure, reproductive cell failures, and neurodegenerative diseases. In addition, we briefly explained the crosstalk between plant exosomes and mammalian cell metabolism in the benefit of cellular stress suppression.