Increasing brain stiffness as we age causes brain stem cell dysfunction. A recent study demonstrates new ways to reverse older stem cells to a younger, healthier state. The research has been published in the journal Nature. The results open many doors of possibility to understanding the aging process, as well as how we might develop much-needed treatments for age-related brain diseases.
Stiff Brain Soft Brain
Muscles and joints tend to become stiff as our bodies age which is why everyday movements become more difficult as we get older. This new study by a multi-disciplinary research team, based at the Wellcome-MRC Cambridge Stem Cell Institute (University of Cambridge) shows how our brains get stiff too and how this age-related brain stiffening has a significant impact on the function of brain stem cells.
The Study
The researchers studied young and old rat brains to understand the impact of age-related brain stiffening on the function of oligodendrocyte progenitor cells (OPCs).
These cells are a type of brain stem cell important for maintaining normal brain function. They are also important for the regeneration of myelin – the fatty sheath that surrounds our nerves, which is damaged in multiple sclerosis (MS). As these cells age, their function declines and that can contribute to MS.
The researchers were curious about whether the loss of function in aged OPCs was reversible. To find out, they transplanted older OPCs from aged rats into the soft, spongy brains of younger animals.
Lo and behold, the older brain cells were rejuvenated, and began to behave like the younger, more vigorous cells.
Next, the researchers developed new materials in the lab with varying degrees of stiffness to study these effects even further. They used these new materials to grow and study the rat brain stem cells in a controlled environment. The materials were engineered to have a similar softness to young brains and a similar stiffness to old brains.
The researchers focused in on investigating Piezo1 – a protein found on the cell surface, which informs the cell whether the surrounding environment is soft or stiff – in order to really understand how brain softness and stiffness influences cell behavior.
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 with Dr. Chalut, explained:
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.
Dr. Susan Kohlhaas, Director of Research at the MS Society, who part funded the research, added:
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 aging and MS, including how to potentially regain lost function in the brain.
