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Abstract
Telomere-shortened mice exhibited cognitive deficits and several brain pathologies.
- Lipofuscinosis, hypomyelination, and microglial atrophy were observed in the brains of telomere-shortened mice.
- Single-nucleus RNA sequencing indicated accelerated aging of glial cells and increased pathways related to microglial senescence.
- DLK1 was identified as a novel ligand associated with microglial senescence in a model using human stem cell-derived microglia.
- Increased levels of soluble DLK1 in cerebrospinal fluid were found in both telomere-shortened and naturally aged mice, with levels returning to normal following microglial depletion.
- Elevating sDLK1 in vivo led to hypomyelination and hindered the progression of oligodendrocyte lineage.
- In human stem cell systems, sDLK1 negatively affected oligodendrocyte maturation and disrupted calcium signaling in excitatory neurons.
Simplified
Longevity & Aging