Longevity Briefs: A Strategy For Boosting Waste Clearance From The Brain

Longevity briefs provides a short summary of novel research in biology, medicine, or biotechnology that caught the attention of our researchers in Oxford, due to its potential to improve our health, wellbeing, and longevity.

The problem:

The central nervous system has its own unique way of removing waste products called the glymphatic system, in which spaces surrounding blood vessels allow cerebrospinal fluid (CSF) to enter and exit the brain. This is a relatively recently discovered system where the arterial pulse essentially ‘massages’ CSF out of the brain tissue and into a venous drainage system, carrying waste products with it. Since dementia-linked misfolded proteins like tau and amyloid beta are also cleared in this way, loss of glymphatic clearance is suspected to be implicated in neurodegenerative diseases like Alzheimer’s.

During deep sleep, glymphatic drainage is greatly enhanced by the rhythmic contraction and relaxation of blood vessels in the brain, resulting in a pumping effect that cycles CSF through the central nervous system. This gave researchers an interesting idea: what if glymphatic clearance could be enhanced simply by changing the concentration of carbon dioxide in the air? Since blood vessels respond to elevated CO2 levels by dilating (which helps clear the CO2 faster and deliver more oxygen), cycling air with varying amounts of CO2 might mimic the effects of deep sleep on glymphatic clearance. While this research has not yet been published (so the full results and data are not available) the concept is interesting enough to be worthy of discussion.

The discovery:

First, researchers used magnetic resonance imaging to observe the brains of sleeping participants in order to measure the frequency of blood vessel contraction and dilation. Based on this, they chose to cycle air every 35 seconds. 30 patients with Parkinson’s disease and 33 healthy participants were then given a treatment in which they alternated breathing normal air for 35 seconds, then air containing 5% CO2 (a little over 100 times the amount in normal air) for 35 seconds. This treatment lasted half an hour, after which researchers collected blood samples. They found that after treatment, there was an increase in levels of amyloid beta, alpha synuclein (a protein associated with Parkinson’s) and other metabolic byproducts of brain activity, suggesting that clearance of waste from the brain into the blood had been enhanced. It’s not entirely clear from the reporting whether this was observed in the healthy participants as well as those with Parkinson’s disease.

The implications:

5% CO2 is safe to breathe and has no significant side effects after just 30 minutes of treatment, so the claim that this is enough to enhance the clearance of misfolded proteins is quite enticing. However, there is no telling whether this would be sufficient to have any real impact on the progression of neurodegenerative diseases. These diseases are characterised by the formation of insoluble plaques that physically disrupt brain tissue and trigger inflammation. These plaques cannot be removed by the glymphatic system – it can only remove soluble proteins before they have formed into plaques. Additionally, even those few treatments that are able to shrink plaques have had disappointing results in clinical trials. If these proteins are truly important drivers of neurodegeneration, then this air cycling treatment should in theory slow down its progression, but I wouldn’t hold your breath (not even for 35 seconds at a time).

For those looking for an easier option, mouse studies suggest that exercise enhances glymphatic function, as does sleeping on one’s side.