Scientists Uncover New Gatekeeper Function of Anti-Aging Molecule

A study published in PNAS details how the protein klotho serves as a gatekeeper that protects the brain from the peripheral immune system, promoting longevity and countering aging-related impairments, reports Medical Xpress . The researchers determined one brain structure, the choroid plexus, contains vastly higher levels of klotho than any other. "We discovered, in mouse models, that klotho levels in the choroid plexus naturally decrease with age," says Lennart Mucke at the Gladstone Institute of Neurological Disease. "We then mimicked this aging process by reducing levels of klotho in this structure experimentally, and we found that depleting this molecule increases brain inflammation." In mice with less klotho in the choroid plexus, inherent immune cells in a key memory center underwent a more aggressive reaction when other parts of the body were exposed to immune challenges that mimic infections. "The barrier between the brain and the immune system seems to break down with low levels of klotho," notes Gladstone's Lei Zhu. "Our findings indicate that klotho helps keep that barrier closed. When levels of this molecule are depleted in the choroid plexus, the barrier becomes more porous and allows immune cells and inflammatory molecules to get through more easily." The team's next step will entail ascertaining whether an increase in klotho levels in the choroid plexus will help suppress age-related cognitive decline.