RRC ID 89529
著者 Tian X, Wu B, Yang K, Wang Y, Li Y, Guan J, Wang K, Zhao Y, Sun K, Ling Y, Zheng J, Xie M, Liu W, Ye X, Li C, Jiang L, Zhao M.
タイトル Psychological stress drives aging-like hematopoietic stem cell dysfunction through a brain-gut-bone marrow axis.
ジャーナル Cell Stem Cell
Abstract Chronic stress influences hematopoietic stem cells (HSCs). However, how psychological stress regulates HSC function remains incompletely understood. Here, we show that psychological stress impairs HSC self-renewal and lymphoid differentiation, inducing aging-like phenotypes. Stress suppresses neuronal activity in the medial prefrontal cortex (mPFC) and periaqueductal gray (PAG), leading to HSC dysfunction, whereas chemogenetic activation of these regions restores HSC function. Psychological stress or chemogenetic inhibition of the mPFC and PAG reduces the abundance of L. reuteri in the gut microbiota and lowers spermidine levels. Mechanistically, spermidine depletion suppresses mitochondrial autophagy, promotes mitochondrial peroxidative stress, and increases ferroptotic stress in HSCs. We further demonstrate that mPFC and PAG activity regulate the intestinal environment through a sympathetic pathway, reducing intestinal mucin levels, L. reuteri abundance, and spermidine levels. These findings identify a brain-gut-bone marrow axis linking psychological stress to aging-like HSC dysfunction through sympathetic regulation of intestinal microbiota and spermidine metabolism.
巻・号 33(7)
ページ 1205-1222.e11
公開日 2026-7-2
DOI 10.1016/j.stem.2026.05.012
PII S1934-5909(26)00204-3
PMID 42392052
MeSH Aging* / pathology Animals Bone Marrow* / pathology Brain* Gastrointestinal Microbiome Hematopoietic Stem Cells* / metabolism Hematopoietic Stem Cells* / pathology Mice Spermidine / metabolism Stress, Psychological* / pathology Stress, Psychological* / physiopathology
オルトメトリクス指標
オルトメトリクス指標項目
最多言及媒体 X(Twitter)
各媒体での言及数の合計 123
過去6か月間でのオルトメトリクス指標の変動値 173.2
リソース情報
実験動物マウス RBRC02975