*During cellular senescence, there is a marked activation of SASP components.
*Apoptosis is a cellular fate quite distinct from cellular senescence, in which extensive mitochondrial outer membrane permeabilization (MOMP) leads to cell death.
*Recently, Stella Victorelli et al. identified a mechanism known as minority MOMP (miMOMP) whereby the DNA nucleoids accumulate in the cytoplasm.
*This process involves the BAX and BAK macropores of the outer mitochondrial membrane, which allow the release of mitochondrial DNA (mtDNA) into the cytoplasm.
*Preliminary results indicate that the removal of mitochondria in senescent cells hinders SASP and that during senescence, miMOMP releases mtDNA into the cytoplasm, triggering the cGAS-STING-SASP pathway.
*The cGAS-STING signaling pathway is a pivotal driver of chronic inflammation and functional decline during the aging process.
*Inhibiting this pathway may result in the reduction of inflammatory responses in aged cells and tissues, as well as the improvement of multiple peripheral organs and the brain.
*The CRISPR-Cas9-mediated deletion of cGAS and STING significantly reduced the secretion of SASP-associated proteins and inflammatory factors.
*MOMP is necessary for apoptosis, but miMOMP can cause cellular senescence without triggering apoptosis.