Researchers at Mayo Clinic discovered that senescent cells accumulate mitochondrial RNA (mtRNA) in the cytosol, activating RNA sensors RIG-I and MDA5, which aggregate the MAVS protein and drive the senescence-associated secretory phenotype (SASP). This cytosolic mtRNA leakage depends on pro-apoptotic proteins BAX and BAK. Blocking these sensors or deleting BAX/BAK significantly reduced SASP factors both in cell culture and in a mouse model of metabolic liver disease (MASH). These findings reveal a previously underappreciated mitochondria-to-cytosol RNA signaling axis that promotes chronic inflammation in aging tissues.
