Longevity Briefs: A Molecule That Reverses Brain Ageing (And How To Make More Of It)

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: As we age, our brain loses its ability to regenerate new cells and maintain its functions. This can lead to cognitive decline, memory loss, and increased risk of neurodegenerative diseases such as Alzheimer’s. There’s clear evidence that exercise can improve brain function and prevent cognitive decline, but due to physical decline, many elderly people cannot exercise regularly. Most people in general would benefit from higher levels of physical activity, and a drug that could mimic some of the effects of exercise could have great benefits for cognitive health, especially for older people.

The discovery: A team of researchers discovered that when aged mice were injected with blood plasma from equally aged mice that had been given access to a running wheel, their cognitive function significantly improved in comparison to those injected with plasma from sedentary mice. They further identified a liver enzyme called Gpld1 that was responsible for transferring the benefits of exercise to the aged brain. They found that Gpld1 levels increased in the blood of aged mice after exercise, and that by genetically boosting the expression of Gpld1 in the liver of aged mice, they were able to improve memory task performance as well as the generation of new brain cells. They also found that aged humans who were more active also had more Gpld1 in their blood on average when compared to sedentary humans.

What exactly is Gpld1, and how does it work? Gpld1 breaks down proteins on the surface of cells, causing the release of signalling molecules that are anchored there. Specifically, it looks like Gpld1 is causing the release of molecules that suppress blood coagulation as well as something called the complement system, which is a network of blood proteins that fight pathogens and promote inflammation. While these systems are obviously important, there’s evidence that they increasingly go awry during ageing.

The implications: This study reveals a mechanism by which exercise can rejuvenate the brain, and opens the possibility of harnessing Gpld1 in order to enhance brain health and prevent cognitive decline in old age. There’s still some debate over the regenerating capability of the human brain. It used to be thought that the adult brain could not grow new brain cells, but more recent research suggests that new brain cells may actually continue to grow even during the 9th decade of life. Either way, one thing is for sure: people of all ages who exercise more have improved cognitive function and are much less likely to get neurodegenerative disease.