GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE315nnn/GSE315101/primaryOK200Transcriptomics Mus musculusHomo sapiensExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE315101GEOGSEfalseSoluble DLK1 secreted by telomere-shortening-induced senescent microglia impairs oligodendrocyte functions and alters neuronal activity [DLK1_snRNA-seq]Aging is a predominant risk factor of neurodegenerative disorders such as Alzheimer’s and Parkinson’s disease. Here, we investigated the impact of telomere shortening, a physiological hallmark of aging, on brain function. Telomere-shortened mice exhibited cognitive decline and exacerbated lipofuscinosis, accompanied by the emergence of senescent microglia with a senescence-associated secretory phenotype and oligodendrocyte lineage cells with impaired maturation. Using iPSC-derived microglia with shortened telomeres, we identified DLK1 as a novel senescence-associated ligand secreted by senescent microglia. Elevated soluble DLK1 was detected in the cerebrospinal fluid of both telomere-shortened and physiologically aged mice, and this increase was abolished by microglial depletion, confirming its microglial origin. Functionally, AAV-mediated expression of sDLK1 in mouse brains induced hypomyelination and disrupted oligodendrocyte differentiation in vivo. In human iPSC-derived systems, sDLK1 impaired late-stage oligodendrocyte maturation and disrupted neuronal calcium signaling. Together, these findings establish replicative microglial senescence as a pathological feature of telomere shortening and identify sDLK1 as one key effector linking senescent microglia to oligodendrocyte dysfunction and neuronal dysregulation during brain aging.2026/07/09GSE315101GSM9421189GSM9421188GSM9421187GSM9421186GSM9421185GSM9421184GSM9421183GSM9421182GSM9421181GSM9421180GSM9421179GSM9421178GSM9421177GSM9421176GSM9421175GSM9421174GSM9421173GSM9421195GSM9421172GSM9421194GSM9421193GSM9421192GSM9421191GSM9421190GSM9867568GSM9867569GSM98675672467624247315101 Mus musculusHomo sapiens