bat STING attenuates aging-related inflammation in female mice.

Bats, notable as the only flying mammals, serve as natural reservoir hosts for various highly pathogenic viruses in humans (e.g., SARS-CoV and Ebola virus). Furthermore, bats exhibit an unparalleled longevity among mammals relative to their size, particularly the bats, which can live up to 40 years. However, the mechanisms underlying these distinctive traits remain incompletely understood. In our prior research, we demonstrated that bats exhibit dampened STING-interferon activation, potentially conferring upon them the capacity to mitigate virus- or aging-induced inflammation. To substantiate this hypothesis, we established the first bat-mouse model for aging studies by integrating bat STING ( STING) into the mouse genome. We monitored the genotypes of these mice and performed a longitudinal comparative transcriptomic analysis on STING and wild-type mice over a 3-year aging process. Blood transcriptomic analysis indicated a reduction in aging-related inflammation in female STING mice, as evidenced by significantly lower levels of pro-inflammatory cytokines and chemokines, immunopathology, and neutrophil recruitment in aged female STING mice compared to aged wild-type mice . These results indicated that STING knock-in attenuates the aging-related inflammatory response and may also improve the healthspan in mice in a sex-dependent manner. Although the underlying mechanism awaits further study, this research has critical implications for bat longevity research, potentially contributing to our comprehension of healthy aging in humans.