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Scientists identify the signature of aging in the brain via the blood-brain-barrier.

A new study from Weizmann Institute researchers has found evidence of a unique signature that may be the missing link between cognitive decline and aging. The scientists believe that this discovery will lead to future treatments that can slow or reverse cognitive decline in older people.

Until a decade ago, scientific dogma held that the blood-brain barrier prevents the blood-borne immune cells from attacking and destroying brain tissue. Yet in a long series of studies, the group showed that the immune system actually plays an important role both in healing the brain after injury and in maintaining the brain’s normal functioning. They found that this ‘brain-immune’ interaction occurs across a barrier that is actually a unique interface within the brain’s territory.

This interface, known as the choroid plexus, is found in each of the brain’s four ventricles, and it separates the blood from the cerebrospinal fluid.  The choroid plexus acts as a ‘remote control’ for the immune system to affect brain activity. Biochemical danger signals released from the brain are sensed through this interface and in turn, blood-borne immune cells assist by communicating with the choroid plexus.  This cross-talk is important for preserving cognitive abilities and promoting the generation of new brain cells.

This finding led the group to suggest that cognitive decline over the years may be connected not only to one’s chronological age but also to one’s immunological age, that is, changes in immune function over time might contribute to changes in brain function, not necessarily in step with the count of a person’s years.

To test this theory, the researchers used next-generation sequencing technology to map changes in gene expression in 11 different organs, including the choroid plexus, in both young and aged mice, to identify and compare pathways involved in the aging process.

That is how they identified a strikingly unique signature of aging that exists solely in the choroid plexus, not in the other organs. They discovered that one of the main elements of this signature was interferon beta, a protein that the body normally produces to fight viral infection.  This protein appears to have a negative effect on the brain.

When the researchers injected an antibody that blocks interferon beta activity into the cerebrospinal fluid of the older mice, their cognitive abilities were restored, as was their ability to form new brain cells. The scientists were also able to identify this unique signature in elderly human brains. The scientists hope that this finding may, in the future, help prevent or reverse cognitive decline in old age, by finding ways to rejuvenate the ‘immunological age’ of the brain.

Source:  Weizmann Institute of Science

 

Immunofluorescence microscope image of the choroid plexus. Epithelial cells are in green and chemokine proteins (CXCL10) are in red.  Credit: Image courtesy of Weizmann Institute of Science.
Immunofluorescence microscope image of the choroid plexus. Epithelial cells are in green and chemokine proteins (CXCL10) are in red. Credit: Image courtesy of Weizmann Institute of Science.

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