Title: A Direct Link Between Genomic Instability and Inflammation in Senescent Cells – Fight Aging!
Aging is marked by chronic sterile inflammation, which disrupts tissue structure and function. Various forms of molecular damage, such as mitochondrial dysfunction, can trigger an innate immune response, leading to inflammation. Researchers have identified a direct link between mutational damage to the genome and inflammation, particularly in senescent cells. This link involves a mitochondria-regulated molecular circuit that connects the p53 tumor suppressor and cytoplasmic chromatin fragments (CCF), activating the cGAS-STING pathway. The study shows that p53 can suppress CCF accumulation and the inflammatory senescence-associated secretory phenotype (SASP), independent of its effects on cell cycle arrest. Additionally, activation of p53 promotes DNA repair, maintaining genomic integrity and reducing inflammation in senescent cells. These findings suggest that targeting the mitochondria-regulated p53-CCF circuit could be a potential intervention for healthy aging.
