组织内巨噬细胞恢复对衰老中性粒细胞的清除限制了器官衰老
组织内巨噬细胞恢复对衰老中性粒细胞的清除限制了器官衰老
作者： 小柯机器人 发布时间：2026/7/17 13:30:00
本期文章：《科学》：Volume 393 Issue 6808
美国斯坦福大学医学院Katrin I. Andreasson研究小组宣布他们提出了组织内巨噬细胞恢复对衰老中性粒细胞的清除限制了器官衰老。相关论文于2026年7月16日发表在《科学》杂志上。
小组发现组织内巨噬细胞（TRMs）是衰老相关器官衰退的中心协调员，通过破坏衰老中性粒细胞的清除，这一过程由免疫调节的前列腺素E2 （PGE2）受体EP2调节。在老年小鼠中，减少TRM EP2信号可以保持年轻时的线粒体健康，防止认知能力下降、虚弱、肌肉减少、肥胖、心脏损伤和全身炎症。血浆蛋白质组学暗示肝脏是年龄相关免疫变化的主要来源，其中TRM EP2信号的减少挽救了中性粒细胞外泌作用，并阻止了邻近细胞的旁分泌应激。在衰老和病变的人体组织中也观察到TRM EP2表达和衰老中性粒细胞的升高。药理学上的EP2抑制恢复了年轻时的中性粒细胞清除，确立了受损的TRM外泌细胞作用是衰老过程中器官衰退的可逆驱动因素。
据了解，衰老破坏了各器官系统的组织稳态。
附：英文原文
Title: Restored clearance of senescent neutrophils by tissue-resident macrophages limits organ aging
Author: Yuting Jessy Tan, Travis E. Conley, Fuwen Yao, Fernando J. García-Marqués, Damilola E. Akinyemi, Van Vuong Dinh, Qian Wang, Abel Bermudez, Jieun Kim, Julia A. Belk, Oliver Soehnlein, Sharon J. Pitteri, Katrin I. Andreasson
Issue&Volume: 2026-07-16
Abstract: Aging disrupts tissue homeostasis across organ systems. Here, we identify tissue-resident macrophages (TRMs) as central coordinators of age-related organ decline through impaired clearance of senescent neutrophils, a process regulated by the immunomodulatory prostaglandin E2 (PGE2) receptor EP2. Reducing TRM EP2 signaling in aged mice preserved youthful mitochondrial fitness and prevented cognitive decline, frailty, sarcopenia, adiposity, cardiac impairment, and systemic inflammation. Plasma proteomics implicated the liver as a major source of age-associated immune change, in which reduced TRM EP2 signaling rescued neutrophil efferocytosis and prevented paracrine stress in neighboring cells. Elevated TRM EP2 expression and senescent neutrophils were also observed in aged and diseased human tissues. Pharmacologic EP2 inhibition restored youthful neutrophil clearance, establishing impaired TRM efferocytosis as a reversible driver of organ decline in aging.
DOI: aea3075
Source: https://www.science.org/doi/10.1126/science.aea3075