This episode of Lifespan News is about exchanging cerebrospinal fluid between young and old mice in order to determine if it has the same longevity effects that blood exchange has.
It has been known for years that parabiosis and using blood from young animals can alleviate or even reverse some age-related changes, including cognitive changes, in old animals. Now scientists have expanded this and found that infusing old mice with cerebrospinal fluid obtained from young mice improves their memory.
Similarly to blood, the composition of cerebrospinal fluid, or CSF, changes with age, but scientists still know very little about the contribution of these changes to aging. One study has shown that in humans, CSF from young healthy donors increases neuronal viability.
In this new study, researchers infused 20-month-old mice with CSF drawn from young mice. Three weeks later, the researchers analyzed the mice’s memory by using a simple test that checks how well the mice remember stimuli associated with discomfort in the past. The researchers found that the mice who received a transfusion of young CSF performed significantly better than controls.
The scientists then ran a transcriptomic analysis of the hippocampus and identified 271 genes that were differentially expressed following the procedure. One of the proteins most upregulated by young CSF was serum response factor, or SRF, a ubiquitous transcription factor that is present not just in the brain but also in skeletal muscle and the heart. Wherever it is expressed, SRF is known to increase cell motility, proliferation, and differentiation. The effects of SRF knockout seen in the study strongly suggest that the effect of young CSF is mediated by SRF and specifically by its induced cytoskeleton growth.
So, something in young CSF was boosting the production of SRF, but there are hundreds of proteins that could be responsible for this. After another battery of experiments, the researchers narrowed their search down to fibroblast growth factor 17, or Fgf17. Interestingly, the levels of Fgf17 in human CSF decrease with age.
Supplementation of this protein showed results similar to treatment with young CSF, and was shown to improve memory in mice. Infusing young mice with Fgf17-blocking antibodies, however, impaired their performance in cognitive tests.
While the rejuvenating properties of young blood are more widely known, the finding that the aged brain can be improved by young CSF opens an entirely new avenue of research into brain aging. Importantly, although both blood and CSF consist of hundreds of components, scientists can isolate the ones responsible for particular outcomes, such as Fgf17, and turn them into therapeutic targets.
Is this a brain aging breakthrough? We’ll need more studies, but this early research into the memory boosting effects of young CSF is promising.
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