Protein from aging immune cells may accelerate brain aging

The work is based on a model of accelerated aging in mice, where the key factor is telomeres: structures at the ends of chromosomes that protect genetic material. They are often compared to plastic tips on shoelaces; they prevent the ends from fraying. With each cell division, telomeres shorten, and when their length falls below a critical threshold, the cell enters a state of senescence — it stops dividing and becomes functionally impaired, while continuing to influence its environment. In the experimental model, telomeres shortened faster than usual, which caused signs of pronounced brain aging to appear in the animals already in early middle age: myelination of nerve fibers decreased, and neuron function deteriorated.

Particularly noticeable changes were recorded in microglia — the immune cells of the brain. Since these cells continue to divide throughout life, their telomeres gradually shorten, which increases the risk of transitioning into a senescent state. It turned out that such aged microglia not only lose their normal function but actively harm neighboring cells: they secrete a number of proteins that disrupt the functioning of surrounding tissues. The key factor in this process turned out to be DLK1. Its presence worsened the condition of neurons and oligodendrocytes, thereby undermining the integrity of neural networks and the protection of nerve fibers.

Importantly, the effects of DLK1 were observed not only in the mouse model. Scientists confirmed its effect on brain cells derived from humans. In addition, in normal (non-modified) mice, the level of DLK1 in the brain increased with age, and analysis of large databases on gene activity in human brain cells showed a similar age dynamics. This suggests that the discovered mechanism is probably relevant for humans as well.

The head of the study, Dr. Li Gan, notes the prospects for further work with DLK1. This protein may become a potential target for therapy that slows down brain aging. One of the strategies that experts plan to test is the neutralization of DLK1 in the brain to assess whether this will help preserve cognitive functions and reduce vulnerability to neurodegenerative diseases. In addition, DLK1 may also be useful in basic science, for example, for creating more accurate models of brain aging in animals.