Thursday, May 12, 2022

In aged mice, the kinds of memory problems common in old age can be reversed, and all it takes is some cerebrospinal fluid harvested from the young

Young CSF restores oligodendrogenesis and memory in aged mice via Fgf17. Tal Iram et al. Nature May 11 2022.

Abstract: Recent understanding of how the systemic environment shapes the brain throughout life has led to numerous intervention strategies to slow brain ageing1,2,3. Cerebrospinal fluid (CSF) makes up the immediate environment of brain cells, providing them with nourishing compounds4,5. We discovered that infusing young CSF directly into aged brains improves memory function. Unbiased transcriptome analysis of the hippocampus identified oligodendrocytes to be most responsive to this rejuvenated CSF environment. We further showed that young CSF boosts oligodendrocyte progenitor cell (OPC) proliferation and differentiation in the aged hippocampus and in primary OPC cultures. Using SLAMseq to metabolically label nascent mRNA, we identified serum response factor (SRF), a transcription factor that drives actin cytoskeleton rearrangement, as a mediator of OPC proliferation following exposure to young CSF. With age, SRF expression decreases in hippocampal OPCs, and the pathway is induced by acute injection with young CSF. We screened for potential SRF activators in CSF and found that fibroblast growth factor 17 (Fgf17) infusion is sufficient to induce OPC proliferation and long-term memory consolidation in aged mice while Fgf17 blockade impairs cognition in young mice. These findings demonstrate the rejuvenating power of young CSF and identify Fgf17 as a key target to restore oligodendrocyte function in the ageing brain.

Popular version, excerpts from Old Mice 'Rejuvenated' With Injections of Brain Fluid From The Young (, by Jacinta Bowler:

While immortality might forever be out of reach, a long, healthy retirement is the stuff dreams are made of.

To that end, a recent study suggests that the kinds of memory problems common in old age can be reversed, and all it takes is some cerebrospinal fluid harvested from the young. In mice, at least.

If this is sounding a little familiar, you might be thinking of a similar series of studies done back in the mid-2010s, which found that older mice could be generally 'rejuvenated' with the blood of younger animals – both from humans and from mice. The FDA even had to warn people to stop doing it.

This new study instead examined the links between memory and cerebrospinal fluid fluid (CSF), and the results show considerable promise, even providing a mechanism for how it works, and highlighting a potential growth factor that could mimic the results.

"We know that CSF composition changes with age, and, in fact, these changes are used routinely in the clinic to assess brain health and disease biomarkers," Stanford University neurologist Tal Iram told ScienceAlert.


To investigate, the researchers, led by Iram, took older mice (between 18–22 months old) and gave them light shocks on the foot, at the same time as a tone and flashing light were activated. The mice were then split into groups, and either given young mouse CSF (from animals 10 weeks old) or artificial CSF.


In experiments like this, if the mice 'freeze' when they see the tone and light, it means they're remembering the foot shock, and are preparing for it to happen again.

In this study, three weeks after the foot shocks were conducted (which the team called "memory acquisition"), the researchers tested the mice, finding that the animals that had been given the CSF from young mice showed higher-than-average freezing rates, suggesting they had better memory.

This was followed up by a battery of other experiments to test the theory, which revealed that certain genes (that are different in young-versus-old CSF) could be used to get the same response. In other words, without needing to extract someone's brain fluid.

"When we took a deeper look into gene changes that occurred in the hippocampus (a region associated with memory and aging-related cognitive decline), we found, to our surprise, a strong signature of genes that belong to oligodendrocytes," Iram told ScienceAlert.

"Oligodendrocytes are unique because their progenitors are still present in vast numbers in the aged brain, but they are very slow in responding to cues that promote their differentiation. We found that when they are re-exposed to young CSF, they proliferate and produce more myelin in the hippocampus."


In the mice, an infusion of a fibroblast growth factor called FGF17 was able to boost oligodendrocyte progenitor cells in a similar way to the CSF injection.

Oligodendrocytes are particularly helpful because they produce myelin, a material that covers and insulates neuron fibers. The infusion of FGF17 was itself able to help the older mice increase memory ability.

While this field of research has a very very long way to go before we can use such insights to increase memory in older humans, the findings are exciting [...]

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