Nature paper claims young CSF fights brain aging in mice

A new Nature paper argues that young CSF fights brain aging.

old mouse young CSF
A new Nature paper argues that CSF from young mice can aid the brains of old mice when infused. Creative Commons image.

Young CSF vs. young blood

CSF is the cerebrospinal fluid that surrounds the brain, including those of young mice. The claim is that when young CSF is injected into the brain/CNS cavity of old mice, it makes the aged brains seem younger. And function better.

I’m somewhat skeptical. I know that you’re shocked to hear that.

Part of the reason for my skepticism is how much the whole “young blood” idea to fight aging has been hyped. For background, the idea behind young blood is that when young people’s blood is infused into old people it might make the aged be physiologically younger including in brain function. The evidence for this is much better in mice than in people, where it is almost nonexistent.

The new paper on young CSF fighting brain aging

Still the new Nature paper from the lab of Tony Wyss-Coray reports that the cerebrospinal fluid of young mice might improve the brain function of older mice. The New York Times also covered the development.

Just the technical side of the paper was quite impressive. It’s remarkable that they could harvest enough CSF to do the studies and get the CSF into the cranial cavities of the “treated” mice. It took a year to get this to work.

The new paper, entitled Young CSF restores oligodendrogenesis and memory in aged mice via Fgf17, also points to the specific growth factor Fgf17 that might be involved. More on that in a minute.

Some limitations

It’s an exciting paper but one that leaves ample room for alternative explanations.

For example, this key section caught my eye:

Mice were then randomly split into two groups and infused with either artificial CSF (aCSF) or young mouse CSF (YM-CSF) for 1 week and remote memory recall was tested 3 weeks after memory acquisition.

YM-CSF infusion resulted in higher average freezing rates following exposure to the tone and light, suggesting better preservation of the remote fear memory

As to the first part, why mainly use artificial CSF as your control? Wouldn’t it make more sense to use the CSF from old mice as the control? I think so.

Artificial CSF is, well, artificial, and could even change brain function in other ways that make data interpretation more complicated. Aged mouse CSF (am-CSF) was only in one experiment that I could see. Maybe it’s hard to get am-CSF in sufficient quantities?

Also, the freezing test is not necessarily an ideal indicator of mouse memory. Perhaps young CSF (vs. aCSF) just makes the mice more scared or does something else that we don’t understand. Note that I’m not a mouse behavioralist. However, it seems like the paper should have had more memory tests conducted. Especially for a Nature paper making a very sexy conclusion. It has only one maze test and that was for only one very specific experiment.

These are the core reasons that I’m not so sure about the biggest conclusion about improved function (meaning memory) due to young CSF.

Stronger parts of the paper

On the other hand, the genomic, molecular and cellular parts of the paper are far more convincing.

The authors nicely show that young CSF impacts specific cells, oligodendrocyte precursors (OPCs). It makes sense that OPCs could have a role in memory related to aging. The transcriptomic studies in the paper also identified OPC-related genes as being substantially changed.

The paper also has strong data implicating SRF signaling. More mechanistically they argue that a specific growth factor called Fgf17 spikes SRF.

These seem to be key mediators of the effects of young CSF on OPC proliferation.

Looking ahead

This paper may be onto something. And it makes sense to me that young CSF would have more growth factors. However, I’m concerned that many folks may get carried away with this idea. We could even see pay-for-play situations involving people getting some CSF product.

Fortunately, I don’t think that’s too likely any time soon. Why?

There’s a good news/bad news element here.

It would be difficult to get enough human CSF to try to sell infusions. Also, how would you safely infuse it? So maybe no crazy folks will try to sell this idea now in clinics before the FDA can pounce? We’ve seen some crazy things in the stem cell clinic arena though.

However, this technical difficulty reality also means that future proven clinical applications, if there ever are any, would be extremely hard to achieve.

CSF-based anti-aging drugs?

This in turns explains, as was the case with young blood, why many people are likely going to hope that a specific CSF growth factor can largely substitute for the actual young spinal fluid. From the NYT times piece biochemist Jeffery Haines is quoted on this kind of idea more generally:

“In general, people are looking for the Holy Grail of aging, and they think there is going to be a magical factor that’s being secreted that’s just going to reverse this thing,” he said. “I don’t think it’s that simple.”

I agree with Haines, but maybe someday there will be a cocktail of factors that can fight aspects of aging.

Maybe as I get older I’ll get less skeptical too. It’s tempting to hope for some major anti-aging drug. So far the best thing seems to be exercise. So any new supposed anti-aging drug would have to perform better than just getting people to be more active. Yet not everyone can substantially increase their activity.

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