Cytosolic DNA Sensing Pathway In Senescence And Aging: Underlying Mechanisms And Targeted Interventions
As we age, our cells undergo a process called senescence, where they stop dividing but remain active, often releasing inflammatory signals. This cellular aging is a major contributor to many age-related diseases. A key player in this process is a cellular alarm system known as the cGAS-STING pathway.
Normally, DNA is safely stored inside the cell’s nucleus or mitochondria. However, when DNA escapes into the main body of the cell (the cytoplasm) due to damage or stress, the cGAS-STING pathway acts as a sensor, detecting this misplaced DNA. This detection triggers a cascade of events, leading to inflammation and the release of a mix of molecules called the senescence-associated secretory phenotype (SASP). These SASP factors can then spread the aging signal to neighboring healthy cells, contributing to chronic inflammation and tissue damage throughout the body.
Interestingly, research indicates that as we get older, the way this pathway functions can change. While its normal activation might become less efficient, a different, “non-canonical” mode of signaling can emerge, still contributing to persistent inflammation and cellular aging. Understanding and targeting this DNA-sensing pathway offers a promising avenue for developing new treatments to combat chronic inflammation, slow down cellular aging, and ultimately improve overall health as we age.
Source: link to paper