Longevity & Aging

Blocking NRF1 Slows Cellular Aging and Extends Lifespan in Mice

Researchers at Nankai University discovered that the transcription factor NRF1 orchestrates the chronic inflammation tied to aging — called inflammaging — by switching on key innate immune genes TBK1 and IRF3. When cells sustain DNA damage, the enzyme ATM phosphorylates NRF1 at a specific site (Ser393), amplifying inflammatory signaling and accelerating cellular senescence. Knocking down NRF1 in mouse fibroblasts reduced senescence markers, cut inflammatory secretions, and restored cell-cycle activity. In aged mice, NRF1 knockdown treatment reduced signs of organ aging and meaningfully extended lifespan. The findings position NRF1 as a druggable target that could suppress the senescence-associated secretory phenotype (SASP) without the off-target tissue damage seen with current senolytic drugs.