NRF1-mediated innate immune response drives inflammaging.

ABSTRACT: Aberrant innate immune responses contribute significantly to cellular senescence, yet the precise interplay between innate immunity and senescence remains poorly characterized. Here, we elucidate the pivotal role of nuclear respiratory factor 1 (NRF1) in orchestrating innate immune responses that drive senescence and the senescence-associated secretory phenotype (SASP). NRF1 deficiency delayed cellular senescence and ameliorated age-related deterioration in multiple organs. Mechanistically, NRF1 enhanced SASP by transcriptionally regulating TBK1 and IRF3, critical nodes in innate immunity essential for senescence induction. Conversely, NRF1 deficiency suppressed innate immune activation, thereby attenuating inflammation associated with senescence and aging. Additionally, DNA damage activat

SUBMITTER: Lei H 

PROVIDER: S-EPMC12727852 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature