Définition
Nrf2 (Nuclear factor erythroid 2-related factor 2) is the master regulator of cellular antioxidant defense. It turns on the production of glutathione, superoxide dismutase, and over 200 other protective enzymes. Activating Nrf2 through diet and training is one of the most efficient anti-aging strategies available.
Under normal conditions, Nrf2 is sequestered in the cytoplasm bound to its inhibitor KEAP1, which targets it for degradation. When the cell experiences oxidative stress, electrophilic compounds, or specific dietary inducers, KEAP1 is modified at cysteine residues, releasing Nrf2. Liberated Nrf2 translocates to the nucleus and binds to antioxidant response elements (AREs) in DNA, activating transcription of hundreds of protective genes.
The genes controlled by Nrf2 include glutathione synthesis enzymes (glutamate-cysteine ligase, glutathione peroxidase), superoxide dismutase, catalase, heme oxygenase-1, NAD(P)H quinone dehydrogenase, and phase II detoxification enzymes. The net effect is a coordinated upregulation of the cell's endogenous antioxidant and detox capacity — far more impactful than any direct antioxidant supplement.
Nrf2 activity declines with age, partly explaining the accumulation of oxidative damage in aging tissues. Restoring Nrf2 cycling is a core strategy in most evidence-based longevity protocols.
The most potent dietary Nrf2 activators: sulforaphane (from broccoli sprouts, which contain 50–100x more sulforaphane precursors than mature broccoli), curcumin with piperine (piperine increases curcumin bioavailability 20-fold), green tea EGCG, resveratrol, quercetin, and other polyphenols. Exercise also activates Nrf2 through the oxidative stress of muscle contraction — this is one of the mechanisms by which exercise produces anti-aging effects despite generating ROS.
For women in perimenopause, declining estrogen reduces endogenous antioxidant defense, making Nrf2 activation through diet and training particularly important during this decade.
Termes associés
Ava Longevity · Built on the Ava Method · MMXXV