Targeting NRF2-KEAP1 axis by Omega-3 fatty acids and their derivatives: Emerging opportunities against aging and diseases

The transcription factor NRF2 and its endogenous inhibitor KEAP1 play a crucial role in the maintenance of cellular redox homeostasis by regulating the gene expression of diverse networks of antioxidant, anti-inflammatory, and detoxification enzymes. Therefore, activation of NRF2 provides cytoprotection against numerous pathologies, including age-related diseases. An age-associated loss of NRF2 function may be a key driving force behind the aging phenotype. Recently, numerous NRF2 inducers have been identified and some of them are promising candidates to restore NRF2 transcriptional activity during aging. Emerging evidence in-dicates that omega-3 (n-3) polyunsaturated fatty acids (PUFAs) and their electrophilic derivatives may trigger a protective response via NRF2 activation, rescuing or maintaining cellular redox homeostasis. In this review, we provide an overview of the NRF2-KEAP1 system and its dysregulation in aging cells. We also summarize current studies on the modulatory role of n-3 PUFAs as potential agents to prevent multiple chronic diseases and restore the age-related impairment of NRF2 function.

Automated summary

The transcription factor NRF2 and its endogenous inhibitor KEAP1 are important for maintaining cellular redox homeostasis. Activation of NRF2 can provide cellular protection against age-related diseases. Recent studies have identified compounds, including omega-3 polyunsaturated fatty acids (PUFAs) and their electrophilic derivatives, that may restore NRF2 function in aging cells. These findings suggest that n-3 PUFAs could be potential agents for preventing chronic diseases and restoring age-related NRF2 impairment.