【摘 要】
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The hippocampus plays a crucial role in leaming and mem-ory,and its progressive deterioration with age is functionally linked to a variety of human neurodegenerative diseases.Yet a systematic profiling of the aging effects on various hip-pocampal cell typ
【机 构】
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State Key Laboratory of Membrane Biology,Institute of Zoology,Chinese Academy of Sciences,Beijing 10
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The hippocampus plays a crucial role in leaming and mem-ory,and its progressive deterioration with age is functionally linked to a variety of human neurodegenerative diseases.Yet a systematic profiling of the aging effects on various hip-pocampal cell types in primates is still missing.Here,we reported a variety of new aging-associated phenotypic changes of the primate hippocampus.These include,in particular,increased DNA damage and heterochromatin erosion with time,alongside loss of proteostasis and ele-vated inflammation.To understand their cellular and molecular causes,we established the first single-nucleus transcriptomic atlas of primate hippocampal aging.Among the 12 identified cell types,neural transiently amplifying progenitor cell (TAPC) and microglia were most affected by aging.In-depth dissection of gene-expression dynamics revealed impaired TAPC division and compromised neuronal function along the neurogenesls trajectory;additionally ele-vated pro-inflammatoryresponses in the aged microglia and oligodendrocyte,as well as dysregulated coagulation path-ways in the aged endothelial cells may contribute to a hostile microenvironment for neurogenesis.This rich resource for understanding primate hippocampal aging may provide potential diagnostic biomarkers and therapeutic interven-tions against age-related neurodegenerative diseases.
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