The human hormone klotho looks like it could have therapeutic potential as a smart drug or life-extending therapy when injected, finds a study in mice.
Everyone produces klotho to some extent, but a lucky few have genes that lead them to produce it in abundance. This has been linked to boosted cognitive abilities and increased longevity. But until now it's not been clear whether these fortunate traits could somehow be given to the genetically unlucky majority.
Scientists at the University of California, San Francisco, have now found that klotho injections can boost the cognition of mice that are genetically engineered to have low klotho levels. This makes them smarter. The findings are published in a study in the journal Cell Reports.
The mice who were given extra klotho performed better in spatial learning and memory tests. A single injection of klotho in older mice was enough to give them a big boost in their navigation skills and ability to learn new tasks.
Exactly how klotho works on the brain to have these effects is a mystery. The part of the protein injected into the mice isn't thought to be able to physically pass through the blood-brain barrier.
On closer investigation, the hormone appeared to be boosting the efficiency of part of a protein found in synapses in the brain. The site of action – called the GluN2B subunit – is known to be involved in strengthening synapses in a way critical for learning and memory.
Klotho could be working indirectly to interact with GluN2B via a pathway involving smaller molecules, or it could be acting via a completely new kind of mechanism involving the brain's peripheral tissues.
Nigel Hooper of the University of Manchester, a cell biologist researching klotho who was not involved in the study, told IBTimes UK that this could be just one of many ways that the hormone works on the body.
"It's an interesting study and raises many interesting questions. It's measuring just one aspect of its action. It may well be having a multitude of other actions – we hope they will be beneficial too," Hooper said.
Despite the many unknowns about the hormone, and that it has only been tested in mice so far, Hooper was optimistic that it could hold promise for therapies in humans.
"Some might argue it doesn't matter how it works, it does work. What does that mean in terms of potential for beneficial to treating human disease?"
But human trials of a klotho-based smart drug or longevity treatment are still a very long way off.
"It's a very large protein, so those sorts of studies would not be easy. It's partly because of the technicalities but also the worries about what such a large protein might be doing.
"But I think the information that this paper raises give one a clear way in as to how one might start coming up with more direct mechanisms using 'better' molecules."