Aging is a slow and progressive natural process that compromises the normal functions of cells,tissues,organs,and systems.The aging of the hypothalamic median eminence(ME),a structural gate linking neural and endocrin...Aging is a slow and progressive natural process that compromises the normal functions of cells,tissues,organs,and systems.The aging of the hypothalamic median eminence(ME),a structural gate linking neural and endocrine systems,may impair hormone release,energy homeostasis,and central sensing of circulating molecules,leading to systemic and reproductive aging.However,the molecular and cellular features of ME aging remain largely unknown.Here,we describe the transcriptional landscape of young and middleaged mouse ME at single-cell resolution,revealing the common and cell type-specific transcriptional changes with age.The transcriptional changes in cell-intrinsic programs,cell-cell crosstalk,and cellextrinsic factors highlight five molecular features of ME aging and also implicate several potentially druggable targets at cellular,signaling,and molecular levels.Importantly,our results suggest that vascular and leptomeningeal cells may lead the asynchronized aging process among diverse cell types and drive local inflammation and cellular senescence via a unique secretome.Together,our study uncovers how intrinsic and extrinsic features of each cell type in the hypothalamic ME are changed by the aging process,which will facilitate our understanding of brain aging and provide clues for efficient anti-aging intervention at the middle-aged stage.展开更多
基金supported by the National Key R&D Program of China(2019YFA0801900 and 2018YFA0801104)the National Natural Science Foundation of China(31771131,81891002,31921002,and 32070972)+3 种基金the Strategic Priority Research Program of Chinese Academy of Sciences(XDB32020000)the Hundred-Talent Program(Chinese Academy of Sciences)the Beijing Municipal Science&Technology Commission(Z210010 and Z181100001518001)the Baoding Technical Program(2141ZF027)。
文摘Aging is a slow and progressive natural process that compromises the normal functions of cells,tissues,organs,and systems.The aging of the hypothalamic median eminence(ME),a structural gate linking neural and endocrine systems,may impair hormone release,energy homeostasis,and central sensing of circulating molecules,leading to systemic and reproductive aging.However,the molecular and cellular features of ME aging remain largely unknown.Here,we describe the transcriptional landscape of young and middleaged mouse ME at single-cell resolution,revealing the common and cell type-specific transcriptional changes with age.The transcriptional changes in cell-intrinsic programs,cell-cell crosstalk,and cellextrinsic factors highlight five molecular features of ME aging and also implicate several potentially druggable targets at cellular,signaling,and molecular levels.Importantly,our results suggest that vascular and leptomeningeal cells may lead the asynchronized aging process among diverse cell types and drive local inflammation and cellular senescence via a unique secretome.Together,our study uncovers how intrinsic and extrinsic features of each cell type in the hypothalamic ME are changed by the aging process,which will facilitate our understanding of brain aging and provide clues for efficient anti-aging intervention at the middle-aged stage.
