Longevity Briefs: Mouse Study Reveals Another Piece Of The Brain Ageing Puzzle

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.

Why is this research important: While not all of us will develop dementia, some degree of cognitive decline is inevitable with age. If we are to develop therapies that can reverse this decline, we need a better understanding of what underlying processes are responsible. There is evidence to suggest that one important aspect of brain ageing is the loss of myelin – the protective insulation that surrounds some nerve fibres and greatly increases the speed of electrical signals. Myelinated nerve fibres form the white matter, which connects different regions of the brain together. Why myelin declines with age isn’t well understood.

What did the researchers do: Researchers compared gene expression in the brains of young mice (1 month old) to aged mice (18 month old). They attempted to identify genes that were the most disrupted during ageing, with a focus on oligodendrocytes – the cells responsible for repairing myelin.

Key takeaway(s) from this research: Genes associated with oligodendrocytes were amongst the most altered genes in the whole brain. Researchers identified a gene of particular interest, Gpr17, which was activated in a specific group of oligodendrocytes responsible for responding rapidly do myelin damage. Using their gene expression data, researchers were then able to identify a compound, LY294002, that might be able to reverse age related changes in gene expression to rejuvenate oligodendrocytes. When administered to 6 month old mice that were previously given a demyelinating agent, they found that LY294002 was able to both increase oligodendrocyte numbers and improve myelin repair compared with control mice.

This research could be an important step for the development of treatments for demyelination diseases like multiple sclerosis (MS), or even eventually slowing or reversing brain ageing. However, these results still need to be confirmed in humans. It is also worth noting that the myelin damage that LY294002 helped to reverse in this study was caused deliberately by the researchers, not by ageing.

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