Scientists uncover new gatekeeper function of anti-aging molecule

The protein has been shown to promote longevity and counteract aging-related impairments. Having more klotho seems to allow for longer and healthier lives, while the depletion of this molecule accelerates aging and may contribute to age-related diseases. Curiously, within the brain, one structure contains vastly higher levels of klotho than all others.

This structure is the choroid plexus, which comprises a complex assembly of cells that produces fluid cerebrospinal fluid and forms an important barrier between the central nervous system and the blood.

A group of scientists at the Gladstone Institutes, led by Lennart Mucke, MD, explains why the plexus choroid contains so much more klotho than other brain regions. In a new study published in the scientific journal PNAS, they showed that the functions of a gatekeeper that shields the brain from the peripheral immune system.

"We discovered, in mouse models, that the levels of the plexus plexus naturally decrease with age," said Mucke, senior investigator and director of the Gladstone Institute of Neurological Disease. "We then mimicked this aging process by reducing levels of this structure experimentally, and we found that depleting this molecule increases brain inflammation."

Mucke and his team further investigated the impact of this phenomenon on other brain regions. They discovered that they are in the choroid plexus, which is an important immune system that has been shown to be more susceptible to infection than mimic infections.

"Said Lei Zhu, a scientist in Mucke's laboratory and first author of the study. "When the levels of this molecule are depleted in the choroidal plexus, the barrier becomes more easily and easily induced."

This type of immune response can be detrimental, because they produce certain factors that have been shown to impair brain functions.

"Mucke, who is also a professor of neurology and neuroscience at UC San Francisco, said:" The molecular changes we observed in our study suggest that they may contribute to cognitive decline in elderly people through brain inflammation. "It could help explain, at least in part, why we often notice deteriorations in cognitive functions in hospitalized seniors when they have infections, such as pneumonia or urinary tract infections.This complication tends to be particularly prominent in patients with Alzheimer's disease, in which inflammation has emerged as a major driver of pathology. "

Now that they have shown that they increase their plexus leads to increased brain inflammation, they can help to reduce their incidence of plexus.

The paper, "Klotho controls the brain-immune system interface in the choroid plexus," was published online by PNAS (Proceedings of the National Academy of Sciences) on November 9, 2018.

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More information:
Lei Zhu et al. Klotho controls the brain-immune system interface in the choroid plexus, Proceedings of the National Academy of Sciences (2018). DOI: 10.1073 / pnas.1808609115