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University of Cambridge researchers reverse brain stem cell ageing

As we age, we might expect our muscles and joints to become stiffer.

Now a team at the Wellcome-MRC Cambridge Stem Cell Institute, part of the University of Cambridge, have uncovered evidence that the same is true in our brains.

Aged rat brain stem cells grown on a soft surface (right) show more healthy, vigorous growth than similar aged brain stem cells grown on a stiff surface (left). The red marker shows brain stem cells, and the green marker indicates cell proliferation. Image: Mikey Segel (15389194)
Aged rat brain stem cells grown on a soft surface (right) show more healthy, vigorous growth than similar aged brain stem cells grown on a stiff surface (left). The red marker shows brain stem cells, and the green marker indicates cell proliferation. Image: Mikey Segel (15389194)

The researchers say age-related brain stiffening has a significant impact on the function of brain stem cells.

But they also found ways to reverse older stem cells to a younger, healthier state.

Their findings, published in Nature, have implications for our understanding of the ageing process and could help in the development of new treatments for age-related brain diseases.

The multi-disciplinary team studied young and old rat brains as they sought to understand the impact of age-related brain stiffening on the function of a type of brain stem cell important for maintaining normal function.

These oligodendrocyte progenitor cells (OPCs) are also important for the regeneration of myelin, the fatty sheath that surrounds our nerves and which is damaged in multiple sclerosis (MS).

The effects of age on these cells contributes to MS but their function also declines with age in healthy people.

The researchers transplanted older OPCs from older rats into the soft, spongy brains of younger animals to see if the loss of function in these cells was reversible.

Incredibly, they found the older brain cells were rejuvenated and began to behave like younger, more vigorous cells.

The team then developed new materials in the lab with varying degrees of stiffness, which were engineered to mimic the relative softness of young and older brains. These were used to grow and study the rat brain stem cells in a controlled environment.

In particular, they investigated the role of Piezo1, a protein found on the cell surface that informs the cell whether the surrounding environment is soft or stiff.

Dr Kevin Chalut, who co-led the research, said: “We were fascinated to see that when we grew young, functioning rat brain stem cells on the stiff material, the cells became dysfunctional and lost their ability to regenerate, and in fact began to function like aged cells.

“What was especially interesting, however, was that when the old brain cells were grown on the soft material, they began to function like young cells - in other words, they were rejuvenated.”

Professor Robin Franklin, who co-led the research, added: “When we removed Piezo1 from the surface of aged brain stem cells, we were able to trick the cells into perceiving a soft surrounding environment, even when they were growing on the stiff material.

“What’s more, we were able to delete Piezo1 in the OPCs within the aged rat brains, which lead to the cells becoming rejuvenated and once again able to assume their normal regenerative function”.

The research was part-funded by the MS Society.

Dr Susan Kohlhaas, director of research at the charity, said: “MS is relentless, painful, and disabling, and treatments that can slow and prevent the accumulation of disability over time are desperately needed. The Cambridge team’s discoveries on how brain stem cells age and how this process might be reversed have important implications for future treatment, because it gives us a new target to address issues associated with ageing and MS, including how to potentially regain lost function in the brain.”

The research was also supported by the European Research Council, the Biotechnology and Biological Sciences Research Council, The Adelson Medical Research Foundation, the Medical Research Council and Wellcome.

Read more

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