Klotho keeps the aging brain stable
There is a protein in your blood that measurably declines as you age. And as it drops, the risk of cognitive deterioration rises.
Klotho was first discovered as a regulator of mineral metabolism. But the researchers show in a new review that it plays a far broader role, particularly in the aging brain. Klotho appears to stabilize multiple processes simultaneously that become dysregulated with age.
The protein is primarily produced in the choroid plexus, a brain structure that filters cerebrospinal fluid. From there it circulates through the body and influences cells at a distance. In the brain, klotho contributes to synapse quality, the formation of new nerve cells, and the insulation of nerve fibers through myelination. These are precisely the processes that deteriorate in neurodegenerative conditions such as Alzheimer’s and Parkinson’s.
Four systems at once
What makes klotho distinctive is the breadth of its influence. The review describes how the protein acts on calcium signaling, mitochondrial energy function, the balance between oxidative stress and repair, and the regulation of immune cells in the brain (neuroimmune regulation). These are four separate systems that each become dysregulated with age.
Low klotho levels in the blood have been associated with cognitive decline in multiple studies. But the review emphasizes that these remain associations for now. Whether raising klotho levels actually prevents cognitive decline has not yet been demonstrated in humans.
From mouse to human
In animal research, the results are promising. Mice with extra klotho expression live longer and show better brain function at older ages. Mice lacking klotho show accelerated aging phenotypes. Several companies are now developing therapies based on klotho fragments or gene therapy to boost its production.
From a longevity perspective, that is noteworthy: if klotho indeed acts as a stabilizer of brain resilience, it is one of the few proteins that appears to influence multiple aging mechanisms simultaneously. That makes it an attractive target, but also a complex one, since broad effects also carry broad risks for intervention.
The review was published in the Korean Journal of Physiology and Pharmacology.