Table 2.

Redox-dependent and -independent effects of NRF2.

Hallmark of Aging	Redox-Dependent Effects of NRF2	Redox-Independent Effects of NRF2
Telomere attrition	Protection of telomeric DNA from oxidative lesions [115]	Enhanced TERT activity to maintain genomic stability [68,87,88]
Genome instability	Preserved DNA integrity by reduced oxidative stress [116]	Induced expression of DNA repair genes [117]
Cellular senescence	Reduced ROS-mediated p21 activation and other stress responses leading to senescence [40]	Regulation of expression of senescence-associated genes [118]
Mitochondrial impairment	Removal of excess mitochondrial ROS, reducing oxidative damage to mitochondrial membranes and proteins Improved redox balance in the electron transport chain [[78], [79], [80], [81]]	Enhanced mitochondrial biogenesis and mitophagy (through PGC-1α signaling), leading to efficient mitochondrial turnover and energy production [81]
Disrupted proteostasis	Preserved protein function by reducing oxidative modifications [51]	Enhanced expression of genes involved in proteostasis such as proteasomal subunits and autophagy-related genes [95,96]
Inflammation	Reduced ROS-driven proinflammatory cascades (e.g., NF-κB activation) [119]	Direct suppression of inflammatory gene expression (e.g., IL-1, TNF-α) [119] Preserved gut barrier function (less endotoxin leakage → lower systemic inflammation [67]
Stem cell exhaustion	Protection of stem cells (HSCs, MSCs, NSCs) from excess ROS, preserving self-renewal [108,109]	Maintained stemness, quiescence, and proper differentiation signals by controlling transcription factors and epigenetic regulators [120]