Regulation of NRF2 signaling pathway and the hallmarks of aging: An overview

Age-related pathologies are tightly associated with increased oxidative stress and inflammation. NRF2, a ubiquitous redox-regulated transcription factor, has a critical function in maintaining cellular homeostasis under stress conditions. NRF2 is at the center of a vast regulatory network, and its signaling pathway is widely recognized as one of the most important cellular defense mechanisms against oxidative stress and inflammatory damage. However, NRF2 activity declines with aging, and this loss appears to be a major risk factor for increasing susceptibility to age-related pathologies. Accordingly, NRF2 signaling has become an attractive pharmacological target for the prevention and treatment of age-associated conditions that are underlined by oxidative stress and inflammation. In this chapter, we provide examples of the interplay between NRF2 pathway and several of the so-called hallmarks of aging. Here, we also review some of the ongoing therapeutic efforts to target NRF2 in aging.