1
0This research identifies microglial senescence as a central driver of brain aging and cognitive decline, particularly through the shortening of telomeres. Using both mouse models and human stem cell systems, the study reveals that aged microglia release a specific protein called soluble DLK1 (sDLK1). This ligand acts as a harmful signal that prevents oligodendrocytes from maturing and forming the myelin insulation necessary for healthy brain function. High levels of sDLK1 also disrupt calcium signaling in neurons, leading to the physiological and memory impairments typically associated with advanced age. By establishing sDLK1 as a key component of the microglial aging profile, the authors provide a new target for treating neurodegenerative diseases and age-related cognitive loss. These findings offer a comprehensive mechanism for how cellular exhaustion in the immune system ultimately compromises the brain's structural and functional integrity.
References:
Liu B, Mahoney M, Feng Y, et al. Senescent microglia with shortened telomeres secrete soluble DLK1 to induce aging-associated hypomyelination and neuronal dysfunction[J]. Neuron, 2026.
