NF-κB

NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) is a family of transcription factors — comprising RelA, RelB, c-Rel, p50 and p52 subunits — that regulate the expression of hundreds of genes involved in inflammation, immunity, cell survival and proliferation. In the canonical pathway, pro-inflammatory signals such as TNF-α, IL-1β, lipopolysaccharide or reactive oxygen species trigger IκB kinase-mediated degradation of inhibitory IκB proteins, releasing NF-κB dimers to translocate to the nucleus and drive target gene expression. NF-κB activity increases with age in multiple tissues and is considered a principal driver of inflammaging, the SASP and age-related immune dysregulation; its activation is also downstream of the cGAS-STING pathway, linking cytosolic DNA sensing to chronic inflammation.