Cause of brain ageing discovered

What makes brains age, and a way to slow the progression of Alzheimer's disease, has been uncovered by US scientists...
10 July 2015

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A key substance involved in brain degeneration has Saggital transection through the human brainbeen uncovered, the first of its kind.

This could give rise to a new method of treating a range of dementia-like illnesses.

Following research into the effects of putting old blood into young mice, UCSF scientist Saul Villeda and his team have identified a specific blood-circulating protein as having a significant impact on the development of age-related brain impairments.

Writing in Nature Medicine journal, they found this protein to increase with age in both mice and humans, while mice lacking in the substance did not develop cognitive impairments to the same degree. By injecting it into the mice, Villeda's team found that the performance of the mice in a range of memory-based tests diminished significantly. They also observed a reduction in the growth of newly-born neurons in the animal's brains.

However, these effects were no longer apparent 30 days after the injections had stopped, suggesting that age-related cognitive decline could be reversible. Further tests will be required to verify whether this is also the case in humans, but if so, there could be potential to avoid some of the symptoms of neurodegenerative diseases such as Alzheimer's.

The protein in question - called β2-Microglobulin (B2M) - has a dual role in the body. It plays an important part in immune response as well as contributing to the development of the nervous system. It is found attached to the surfaces of almost all nucleated cells, appearing to 'drop off' with age and accumulate in the bloodstream.

Previous work in the field involved surgically attaching the circulatory systems of two mice of different ages in order to mix their bloodstreams, a technique known as heterochronic parabiosis. This indicated that putting old blood into a young mouse stimulated brain degeneration, but it was not known exactly which substance or substances drove these changes.

Using a combination of mazes and 'fear conditioning' tests (in both of which older mice are known to perform less well), Villeda showed that young mice demonstrated inferior memories after having gone through a program of injections of B2M. Their performances became more similar to those of much older animals.

Moreover, mice genetically modified to have low levels of B2M did not develop memory loss with age in the same way.

This is the first substance found that appears to have a direct causal effect on age-related brain degeneration, and has brought hope for a fresh approach to the development of anti-ageing techniques. Whereas previous investigations have focused largely on promoting youthful brain characteristics, this discovery could lead to a preventative method, concentrating on the use of antibodies either to block or destroy B2M and avoid a build up of the protein.

We are, however, still in the dark as to exactly why these B2M has these effects. Nonetheless, this discovery represents a significant development in the ongoing quest to conquer ageing.

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