STING deficiency does not rescue short-telomere mediated aging phenotypes and longevity in TERC or TERT telomerase deficient mice

More recently a role of the c-GAS-STING in senescence and in response to short telomeres has been also proposed. To address the role of the cGAS-STING pathway in the age-related pathologies and decreased longevity associated to short and dysfunctional telomeres, here we have generated double mutant mice for STING and increasing generations of telomerase deficiency, either owing to deficiency in the telomerase RNA component, TERC, or in the reverse transcriptase component (TERT).

Our results with both telomerase-deficient mouse cohorts show that STING deficiency does not rescue any of the major phenotypes associated to short telomeres, including decreased body weight, infertility, and a plethora of degenerative pathologies. Importantly, STING deficiency does not rescue the progressively decreased maximum and median lifespan of increasing generations of Terc or Tert deficient mice. These findings indicate that STING does not mediate aging phenotypes associated to short telomeres in mammals.