STING促进组织的恒温维护,并与衰老一起赋予长寿
Jacob W Hopkins1,2, Katherine B Sulka1,2, Machlan Sawden1,2
1Department of Immunology, Tufts University, Boston, MA 02111.
bioRxiv : the preprint server for biology
|April 22, 2024
概括
基础性STING信号传递对于在衰老过程中维持组织功能和寿命至关重要. 刺痛缺陷缩短了寿命,破坏了组织平衡,挑战了刺痛仅仅是病理性的观点.
科学领域:
- 免疫学 免疫学 免疫学
- 衰老研究研究 衰老研究
- 分子生物学分子生物学
背景情况:
- 老化组织中的局部免疫过程驱动功能障碍,但潜在的途径尚不清楚.
- 细胞质DNA传感途径涉及cGAS和STING调节炎症,并与衰老模型有关.
- 在生理衰老中cGAS/STING的作用仍然未被探索,尽管STING的流行率和功能多态性.
研究的目的:
- 研究cGAS/STING通路在生理衰老过程中的作用.
- 确定STING缺乏对寿命,组织炎症和衰老过程中的免疫特征的影响.
- 阐明通过STING信号维持组织平衡并支持长寿的机制.
主要方法:
- 在生理衰老过程中对SING充足和SING缺乏的小鼠进行比较分析.
- 评估寿命,血清细胞因子水平,组织透物和组织成分.
- 分析免疫基因表达 (炎症性,干扰素刺激的基因,衰老) 和老化组织 (心脏,肝脏,脏) 中的细胞相互作用网络.
主要成果:
- 刺缺乏症显著缩短了小鼠的寿命,增加了促炎性细胞因子,改变了组织组织学.
- 衰老的组织表现出明显的"免疫指纹" (炎症,ISG,衰老基因子集),由肌和髓质细胞打印.
- 刺缺陷失调这些免疫指纹,改变了肌/骨髓细胞相互作用,组织架构混乱,减少了组织寄居巨细胞 (TRM) 种群.
结论:
- 在生理衰老过程中,基底性STING信号对组织稳定和生物体长寿至关重要.
- 与之前的假设相反,STING信号在衰老过程中具有保护性作用,而不是主要具有病理性的作用.
- 针对STING通路需要谨慎,因为可能会对老龄化健康产生不可预测和病态后果.
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