Half of mice lacking STING, a protein that triggers inflammation in response to DNA in the cytoplasm, survived to 773 days compared with 712 for normal mice, and older mice lacking STING had less liver inflammation and scar tissue, a preprint reports

Half of mice lacking STING, a protein that triggers inflammation in response to DNA in the cytoplasm, survived to 773 days compared with 712 for normal mice, and older mice lacking STING had less liver inflammation and scar tissue, a preprint reports

On October 19, Vera Gorbunova and Andrei Seluanov of the University of Rochester, John Sedivy of Brown University, and their colleagues posted a study on bioRxiv, a server for manuscripts that have yet to undergo peer review. They compared the lifespans of 62 mice whose STING gene had been disabled from birth and 61 normal mice.

STING is the second component of a signaling pathway that responds to DNA in the cytoplasm. The sensor cGAS detects this DNA and produces the signaling molecule cGAMP. STING binds to cGAMP and activates the interferon response, the cell's antiviral alarm system. This pathway also responds to the cell's own DNA, which becomes more abundant in the cytoplasm with age. Sources include mitochondria, LINE1 sequences (parts of the genome that can copy themselves), and fragments of nuclear DNA. The preprint's authors describe this pathway as a major driver of chronic inflammation during aging. A 2023 study in Nature showed that blocking STING reduces inflammation in the organs and brains of old mice.

In 2019, Gorbunova, Seluanov, and Sedivy showed that DNA copies of LINE1 accumulate in the cytoplasm of short-lived mice lacking the protein SIRT6 and trigger an interferon response through cGAS. They expected mice lacking cGAS to live longer, but reported the opposite in Nature Aging: half of these mice survived to 1,64 years, compared with 2,01 for normal mice. The authors proposed that cGAS helps keep DNA tightly packed and LINE1 inactive in the nucleus. Without cGAS, LINE1 becomes active, more copies of its DNA accumulate in the cytoplasm, and inflammation increases. LINE1 remained inactive in tissues from mice lacking STING, so the authors reasoned that disabling STING might extend lifespan while preserving DNA packaging in the nucleus.

Mice lacking STING, the second component of the same pathway, lived longer: half survived to 773 days, compared with 712 for normal mice. The difference was 61 days, or 8,6%. Males lacking STING also showed less graying of their coats; the authors note that graying has been linked to immune signaling in hair follicles.

Examination of tissue sections from the heart, lungs, liver, kidneys, and pancreas revealed a noticeable difference only in the liver. Old mice lacking STING had fewer clusters of inflammatory cells there. In males, collagen, which forms the structural basis of scar tissue and was visualized using Masson's stain, occupied about 21% of the section area in normal mice and 2–3% in mice lacking STING (four males per group). Previous work in two mouse models of fatty liver disease found less inflammation and scarring in animals lacking STING.

In the livers of normal mice, STING gene expression increases with age, and the active form of the protein is more abundant at 25 months than at 18. In old males lacking STING (three mice per group), genes involved in the interferon response, leukocyte migration, and collagen metabolism were less active than in normal mice.

Another group found the opposite effect in the brain. In 2025, Shruti Sharma's team at Tufts University reported in Cell Reports that aging mice lacking STING had greater disruption of the blood-brain barrier (the protective barrier formed by the brain's blood vessels), developed microbleeds, and showed impaired movement.

“Our findings suggest that the inflammatory processes sustained by STING may actually be necessary for the brain to remain healthy and maintain its balance in old age,” Sharma says.

The drug omaveloxolone already breaks down STING in old mice.