Researchers Discovered a New Gatekeeper Function of Protein Klotho, an Anti-aging Molecule

Protein Klotho

In the latest study, a group of researchers at the Gladstone Institutes have discovered a new function of protein klotho, an Anti-aging Molecule that generally promote longevity and curb age-related impairments in human beings.

Presence of high amount of protein klotho in the body allow for healthier and longer lives whereas its depletion results into rapid aging and age-related diseases. Interestingly, choroid plexus of the brain contains excessively higher level of this molecule than all the others. Main function of this structure of the brain is to secrete cerebrospinal fluid while forming a barrier between the blood and the central nervous system with its complex assembly of cells.

According to Lennart Mucke, MD who led the research team, they investigated why choroid plexus contains relatively high amount of protein klotho compared to other regions of the brain. It showed that the molecule acts as a gatekeeper that protects the brain from the peripheral immune system.

The new findings were published in recent issue of the journal PNAS. In mouse models, it was discovered that the levels of klotho in choroid plexus decrease with age. When mimicking the same aging process by experimentally reducing klotho levels in this brain structure, researchers reported, decrease in the molecule increase brain inflammation.

Further, the team analyzed the impact of this event on other regions of the brain. With reduced level of klotho in the choroid plexus of the mice, the researchers discovered that certain innate immune cells required for memory functions started to react aggressively when other body parts were exposed to immune challenges, mimicking infections.

First author of the study Lei Zhu said that the important barrier between the brain and the immune system seems to break down with decreasing level of klotho. Their findings imply that the molecule is responsible for keeping the barrier closed and its depletion cause the barrier to become more porous, allowing inflammatory molecules and immune cells to enter more easily, he added.

Such aggressive response from the immune cells can be harmful as they promote particular factors affecting functions of the brain. Study observations suggest that depletion of klotho in choroid plexus might cause cognitive decline in aging population. It further explains the deteriorations in cognitive functions of seniors who are hospitalized due to certain infections such as urinary tract infection or pneumonia.

After the discovery, the researchers are planning their next set of trial to determine if increasing the level of protein klotho would help suppress impact of age-related brain impairments.

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Rahul Pandita

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