Aged brain immune cells secrete a damaging protein
The brain’s own immune cells can become damaged with age. When they do, they release a protein that disrupts surrounding brain tissue. Researchers have now identified that signal as a potential driver of cognitive decline.
Microglia are the resident immune cells of the brain. They clear waste, fight infection, and support neurons. But with aging, microglia can themselves enter a senescent state, one in which they stop functioning normally and instead secrete harmful substances. The researchers found that senescent microglia secrete a protein called DLK1, and that this protein causes dysfunction in the surrounding brain tissue.
What does DLK1 do in the brain?
DLK1 (delta-like non-canonical Notch ligand 1) is a signalling protein normally involved in cell development. In the aging brain, it appears to be activated in the wrong place at the wrong time. Microglia in a senescent state produce elevated levels of this protein, which then disrupts neighbouring brain cells.
This fits a broader pattern in aging research. Senescent cells, those that have stopped dividing but have not died, actively release substances that damage their local environment. This is known as the SASP, or senescence-associated secretory phenotype. That DLK1 is part of this pattern in microglia is a new finding, though its exact consequences for cognition in humans have not yet been established.
A potential target for future therapies
If senescent microglia contribute to cognitive decline via DLK1, that identifies a possible therapeutic target. Approaches that remove senescent cells or block their damaging secretions are already being investigated in broader aging research. This study adds a specific mechanism relevant to the brain.
An important caveat: the findings come from mouse models and laboratory studies. Whether blocking DLK1 would work in humans, and whether cognitive effects could be reversed this way, remains unknown. Still, identifying a specific molecular signal is a step that makes follow-up research more tractable.
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Search terms: microglia senescence DLK1, SASP neuroinflammation aging, cognitive decline brain immune cells