Removing the immune alarm protein STING did not rescue mice with short telomeres
Removing the immune alarm protein STING did not rescue mice with short telomeres
On August 6, the authors of a Cell Reports paper tested whether removing STING could reduce the effects of telomere shortening in mice. In two independent telomerase-deficient mouse lines, this genetic intervention neither improved tissue health nor extended lifespan.
Telomeres are protective regions at the ends of chromosomes. When they become too short, the cell recognizes them as DNA damage. Cell division slows, which makes tissue renewal more difficult. STING activates an immune alarm response when a cellular sensor detects DNA outside the nucleus. Researchers therefore considered it a possible link between damaged telomeres and inflammation.
This hypothesis had strong prior support. In a 2025 study of telomerase-deficient zebrafish, removing STING reduced signs of premature aging, restored fertility, and extended lifespan. The new study tested whether the same effect would occur in mammals.
The authors used two telomerase-deficient mouse lines. Telomerase is the enzyme that maintains telomeres. One line lacked TERC, the RNA component of telomerase, while the other lacked TERT, its catalytic subunit. Both lines were crossed with mice lacking STING. These distinct genetic defects produce the same outcome, short telomeres, which allowed the researchers to test the role of STING specifically in this type of damage.
In both lines, removing STING neither restored body weight nor extended lifespan, and intestinal damage persisted. The p53–p21 pathway remained active in the intestine. This DNA damage response slows cell division. Short telomeres therefore continued to impair tissue renewal even though STING was no longer produced.
In another experiment with TERC mice, researchers weakened the damage signal directly at the telomeres without lengthening them, and hematopoietic bone marrow cells recovered more effectively. Removing STING did not produce this effect. Two independent mouse models showed that this protein was not required to connect short telomeres with tissue damage and reduced lifespan.