Myotis bat STING attenuates aging-related inflammation in female mice.

IF 4 1区 生物学 Q1 ZOOLOGY
Xi Wang, Jing-Kun Jia, Qi Wang, Jing-Wen Gong, Ang Li, Jia Su, Peng Zhou
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Abstract

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 Myotis 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 in vivo bat-mouse model for aging studies by integrating Myotis davidii bat STING ( MdSTING) into the mouse genome. We monitored the genotypes of these mice and performed a longitudinal comparative transcriptomic analysis on MdSTING and wild-type mice over a 3-year aging process. Blood transcriptomic analysis indicated a reduction in aging-related inflammation in female MdSTING mice, as evidenced by significantly lower levels of pro-inflammatory cytokines and chemokines, immunopathology, and neutrophil recruitment in aged female MdSTING mice compared to aged wild-type mice in vivo. These results indicated that MdSTING 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.

蝙蝠STING能减轻雌性小鼠与衰老有关的炎症。
蝙蝠是唯一会飞的哺乳动物,是人类各种高致病性病毒(如 SARS-CoV 和埃博拉病毒)的天然宿主。此外,相对于其体型,蝙蝠在哺乳动物中表现出无与伦比的长寿,尤其是蝠鲼,寿命可达 40 年。然而,人们对这些与众不同的特性背后的机理仍然知之甚少。在我们之前的研究中,我们证明蝙蝠表现出抑制 STING 干扰素激活的特性,这可能赋予它们减轻病毒或衰老引起的炎症的能力。为了证实这一假设,我们通过将大威蝠STING(MdSTING)整合到小鼠基因组中,建立了第一个用于衰老研究的体内蝙蝠-小鼠模型。我们监测了这些小鼠的基因型,并对 MdSTING 和野生型小鼠进行了为期 3 年的纵向比较转录组分析。血液转录组分析表明,雌性 MdSTING 小鼠与衰老相关的炎症有所减轻,这表现在与衰老的野生型小鼠相比,衰老的雌性 MdSTING 小鼠体内促炎细胞因子和趋化因子、免疫病理和中性粒细胞募集水平明显降低。这些结果表明,敲入 MdSTING 能减轻与衰老相关的炎症反应,还能以性别依赖的方式改善小鼠的健康寿命。尽管其潜在机制还有待进一步研究,但这项研究对蝙蝠长寿研究具有重要意义,有可能有助于我们理解人类的健康衰老。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Zoological Research
Zoological Research Medicine-General Medicine
CiteScore
7.60
自引率
10.20%
发文量
1937
审稿时长
8 weeks
期刊介绍: Established in 1980, Zoological Research (ZR) is a bimonthly publication produced by Kunming Institute of Zoology, the Chinese Academy of Sciences, and the China Zoological Society. It publishes peer-reviewed original research article/review/report/note/letter to the editor/editorial in English on Primates and Animal Models, Conservation and Utilization of Animal Resources, and Animal Diversity and Evolution.
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