TXNRD1 drives innate immune response in senescent cells and promotes age-associated inflammation II

Sterile inflammation, also known as “inflammaging”, is a hallmark of tissue ageing. Cellular senescence contributes to tissue aging in part through secretion of proinflammatory factors known as senescence-associated secretory phenotype (SASP). Thioredoxin reductase 1 (TXNRD1) genetic variability is associated with aging and age-associated phenotypes such as late-life survival, activity of daily living, and physical performance at old age. TXNRD1’s role in regulating tissue ageing has been attributed to its enzymatic role in reducing reactive oxygen species. Here we show that TXNRD1 drives SASP and inflammaging through the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) innate immune response pathway independent of its enzymatic activity RNA-seq of Young and Aged mice, with Aged mice under control and TRi-1 or Auranofin treatment