Longevity & AgingRibonucleotides Sneaking Into Mitochondrial DNA Spark Aging Inflammation
Researchers discovered that nucleotide imbalance causes ribonucleotides to be erroneously inserted into mitochondrial DNA (mtDNA), destabilizing it and causing fragments to leak into the cytosol. This activates the cGAS–STING innate immune pathway, driving chronic inflammation. The phenomenon was observed in aged mouse kidneys, in mice lacking the mitochondrial exonuclease MGME1, in cells lacking the protease YME1L, and in senescent cells. Critically, supplementing cells with deoxyribonucleosides reduced ribonucleotide misincorporation and suppressed the inflammatory senescence-associated secretory phenotype (SASP), pointing toward a potential therapeutic strategy for age-related inflammatory diseases.
