Researchers have uncovered a potential mechanism linking cellular senescence to brain aging and neurodegeneration. In a mouse model of accelerated aging, brain immune cells known as microglia entered a dysfunctional, non-dividing senescent state and began releasing a protein called DLK1.

The researchers found that DLK1 can disrupt the function of nearby neurons and oligodendrocytes, cells responsible for supporting nerve function and maintaining the protective myelin coating around nerve fibers. The accelerated-aging mice also showed features commonly associated with advanced brain aging, including reduced myelination and impaired neuronal activity.

DLK1 levels were also found to increase with age in normal mice, while human brain-cell data showed evidence of similar age-related changes. Further experiments demonstrated that DLK1 could negatively affect both mouse and human-derived brain cells.

These findings suggest that senescent microglia and DLK1 signaling may contribute to cognitive decline, brain aging, and increased susceptibility to neurodegenerative diseases, including Alzheimer’s and Parkinson’s disease.

The study also highlights DLK1 as a potential target for future therapies aimed at protecting the aging brain. Researchers plan to investigate whether blocking or neutralizing this protein could reduce the harmful effects of cellular senescence, preserve brain function, and potentially slow aspects of age-related cognitive decline. Further research will be needed to determine whether this approach could be beneficial in humans.

Source: https://news.cornell.edu/stories/2026/08/protein-secreted-immune-cells-may-help-drive-brain-aging