GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE315nnn/GSE315100/suppl/GSE315100_raw_counts_all_samples_DLK1_Bang.txt.gzftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE315nnn/GSE315100/primaryOK200TranscriptomicsHomo sapiensExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE315100GEOGSEfalseSoluble DLK1 secreted by telomere-shortening-induced senescent microglia impairs oligodendrocyte functions and alters neuronal activity(ipsc_cell)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.2026/07/09GSE315100GSM9421149GSM9421148GSM9421169GSM9421147GSM9421146GSM9421168GSM9421145GSM9421167GSM9421166GSM9421144GSM9421165GSM9421164GSM9421163GSM9421162GSM9421161GSM9421160GSM9421159GSM9421158GSM9421157GSM9421156GSM9421155GSM9421154GSM9421153GSM9421152GSM9421151GSM9421150GSM9421171GSM942117024676315100Homo sapiens