Misplaced DNA inside cells drives aging inflammation
In aging cells, DNA ends up in the wrong place. The immune system recognises it as an outside threat and raises the alarm.
DNA and RNA normally belong in the cell nucleus and in mitochondria (the cell’s energy-producing structures). As cells age, their internal organisation deteriorates. Fragments of DNA and RNA drift into the cytosol, the fluid that fills the rest of the cell. Proteins in the cytosol that normally detect viruses and bacteria respond to these misplaced fragments as if an infection is underway. They activate an inflammatory response. The researchers describe this mechanism as a major driver of the chronic inflammation characteristic of aging.
cGAS-STING as the trigger
One of the main sensors that raises this alarm is the cGAS-STING system. This system normally detects viral or bacterial DNA in the cytosol and then activates inflammatory signals. In aged cells, the same sensors become permanently activated by DNA fragments leaking from the nucleus or from damaged mitochondria. The result is a persistent, low-level activation of the immune system.
A parallel process occurs with RNA. RNA fragments that leak from mitochondria, or that arise from disrupted processing of genetic information, activate other sensors in the cytosol. Together, both routes create a continuous signal that sustains inflammation even when there is no infection or tissue damage.
Misplaced genetic material as a longevity target
This review, published via Fight Aging!, describes existing literature and formulates mechanistic hypotheses. The researchers suggest that reducing cytosolic DNA and RNA may be a viable target for interventions that dampen aging-related inflammation. Whether this can be achieved safely and effectively in humans remains to be demonstrated. For longevity research, it is relevant because it provides a mechanistic explanation for a process long considered a risk factor: chronic, low-grade inflammation in later life.