Longevity Briefs: Using Light To Clear Toxic Compounds From The Brain

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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:

There is increasing scientific interest in using different wavelengths of light, particularly infrared light, in various health applications. Longer wavelength light such as infrared penetrates deeper into tissues, where it is absorbed by proteins and may change their properties in beneficial ways. The proposed benefits are numerous, from improved skin health to enhanced cognitive function, but these applications remain experimental in humans, with the vast majority of the evidence being restricted to animal studies.

In this study, researchers present evidence from mice that infrared laser use can enhance cognitive function by affecting advanced glycation end products (AGEs) in the brain. AGEs are molecules produced when sugars react with proteins or fats, either during cooking or naturally within the body, especially when blood sugar is high. AGEs are harmful because they can permanently link proteins or other molecules together, preventing those molecules from fulfilling their function and making them harder to break down. AGEs are perhaps best known for their role in skin ageing, but are also associated with age related diseases like cardiovascular and neurodegenerative diseases.

The discovery:

Researchers found that they could use near-infrared lasers to clear AGEs from the brains of mice, thereby improving some aspects of cognitive function.

They first exposed mice to D-galactose, a sugar that promotes AGE accumulation. They then treated the mices’ brains with 1275-nanometer wavelength light, which is termed ‘near-infrared’. Importantly, no invasive surgery was necessary to deliver this treatment – the laser was able to penetrate the skulls of the mice to reach the brain. The mice received 61 minutes of laser treatment per day, in 17 minute cycles for a total of two weeks. As controls, one group of mice was not treated with D-galactose, while another group was treated with D-galactose but was not given laser treatment. The sample sizes were relatively small, with 10 or fewer mice per group.

The researchers found that mice treated with the near-infrared laser had significantly improved cognitive function compared to untreated mice. They performed significantly better in a water maze test (where mice try to find a platform under the water as quickly as possible). In fact, the laser treated mice performed just as well as the mice that had not been treated with D-galactose. However, there was no significant difference in swimming speed between any of the groups, suggesting that the improved performance of the laser treated mice was due to cognitive function, not physical function. The laser treated mice also performed significantly better in the novel object recognition test which, as the name suggests, is a test of a mouse’s ability to recognise new objects.

The researchers performed post-mortem analyses of the mices’ brains in an attempt to identify the underlying changes that could be responsible for the improved cognitive performance. They found that laser-treated mice had less AGE accumulation in their cerebral cortices, fewer markers of cell death, and reduced levels of inflammation and oxidative stress.

The implications:

It seems as though near-infrared laser therapy could be a viable non-invasive strategy to improve the clearance of AGEs from the brain, thereby improving cognitive function. The main mechanism for this involved nitric oxide, which is released by endothelial cells to trigger the dilation of blood vessels and lymphatic vessels (the network that allows immune cells, proteins and waste products to drain from tissues throughout the body). Near infrared light stimulates the production of nitric oxide by lymphatic endothelial cells, so it promoted the widening of the lymphatic vessels in the brain, allowing for better drainage of toxic products like AGEs. In support of this as the main mechanism, the researchers found that using a drug to block the synthesis of nitric oxide prevented the near-infrared light from having any effect.

Such a therapy might not work as well in humans. Humans have both thicker skulls and thicker cerebral cortices when compared to mice, which means that near infrared radiation would not be able to penetrate as deeply into the brain. That said, some small clinical trials have already reported benefits associated with transcranial near-infrared light in both dementia patients and ageing but otherwise healthy people. We’re still awaiting larger trials to confirm these benefits.

Note that while many commercial ‘infrared therapy’ devices are sold, they may not deliver the correct wavelengths of light at the necessary dose to be effective when applied to the scalp. This study used a wavelength of 1275-nanometer at a dose of 10 mW/cm² to the scalp. Doses that are too high may also pose a danger by generating excessive heat.