Myotis bat STING attenuates aging-related inflammation in female mice

As the only flying mammal, bats serve as natural reservoir hosts for numerous highly pathogenic viruses in humans (e.g., SARS-CoV or Ebolavirus). Furthermore, bats boast an unparalleled longevity among mammals relative to their size, particularly the Myotis bats that 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 inaugural in vivo bat-mice model for aging studies by integrating Myotis davidii bat STING (MdSTING) into the mice genome. We monitored genotypes and conducted a longitudinal comparative transcriptomics analysis on MdSTING and wildtype mice over a 3-year aging process. Our plasma transcriptomics analysis indicated a reduction in aging-related inflammation in female MdSTING mice, and the finding was further corroborated by in vivo data, demonstrating significantly lower levels of pro-inflammatory cytokines or chemokines, immunopathology, and neutrophil recruitment in aged female MdSTING mice compared to aged wild-type mice. These results showed that MdSTING knock-in attenuates aging-related inflammatory response and may also improve the healthspan in mice in a sex-dependent manner. Although the mechanism behind awaits further study, this work holds critical implications for bat longevity research, contributing to our comprehension of healthy aging in humans.