Définition
NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) is the master transcription factor of inflammation. When activated, it drives production of inflammatory cytokines, immune cell recruitment, and tissue damage signaling. Chronic NF-κB activation is a core driver of inflammaging and age-related decline.
NF-κB is normally held inactive in the cytoplasm by its inhibitor IκB. When cells encounter inflammatory stimuli — bacterial LPS, viral components, cytokines (TNF-alpha, IL-1), ROS, or damaged cellular debris — IκB is phosphorylated and degraded, releasing NF-κB. The liberated transcription factor enters the nucleus and activates hundreds of inflammation-related genes including IL-6, TNF-alpha, COX-2, iNOS, and adhesion molecules.
Acute NF-κB activation is protective — it coordinates the immune response to infection and injury. The problem is chronic low-grade activation, which drives inflammaging and contributes to the pathogenesis of virtually every age-related condition.
NF-κB activity is regulated by a web of inputs. It is activated by oxidative stress, chronic infection, gut dysbiosis producing LPS leakage, visceral adiposity (inflammatory cytokines from visceral adipocytes), chronic psychological stress (via cortisol resistance), sleep deprivation, and senescent cell accumulation (SASP-driven activation). It is suppressed by estrogen (one mechanism for estrogen's anti-inflammatory effects), sirtuins (SIRT1 directly deacetylates NF-κB), and many plant compounds.
The NF-κB / Nrf2 axis is a core theme in anti-inflammatory nutrition — the goal is to suppress NF-κB while activating Nrf2. The same compounds often accomplish both: curcumin, sulforaphane, quercetin, EGCG, and omega-3 fatty acids. For women post-menopause, the loss of estrogen-mediated NF-κB suppression makes dietary control of this pathway more consequential.
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