New research, published today at Nature, reveals how increased brain stiffness as we age causes brain brain dysfunction and demonstrates new ways to return older stem cells to a younger, healthier state.
The results have far-reaching implications for how we understand the aging process and how we can develop much needed treatments for age-related brain diseases.
As our bodies get older, muscles and joints can become stiff, making daily movements more difficult. This study shows that the same is true in our brains and that age-related brain strengthening has a significant impact on brain stem cell function.
A multidisciplinary research team, based at the Velikom-MDC Cambridge Institute of Stem Cells (University of Cambridge), has studied young and old rat brains to understand the impact of age-related brain firming on brain function. progenitors (OPCs).
These cells are a type of brain stem cell that is important for maintaining normal brain function and for the regeneration of myelin – the fatty lining that surrounds our nerves, which is damaged in multiple sclerosis (MS). The effects of age on these cells contribute to MS, but their function also decreases with age in healthy people.
To determine if loss of function in older OPCs is reversible, researchers transplanted older OPCs from rats to rats in the soft, spongy brains of younger animals. Remarkably, the older brain cells rejuvenated and began to behave like younger, more intense cells.
To investigate this further, the researchers developed new materials in the laboratory with varying degrees of stiffness and used them to grow and study rat brain cells in a controlled environment. The materials were designed to have a similar softness to either young or old brains.
To fully understand how the softness and firmness of the brain affect cell behavior, the researchers examined Piezo1 – a protein on the cell surface that alerts the cell whether the environment is soft or hard.
Dr Kevin Falut, who led the research, said: "We were fascinated to see that when we were growing young, functioning stem cells of the brain of the hard material, the cells became dysfunctional and lost their ability to regenerate and in fact began to function. like aging cells. What was particularly interesting was that when the old brain cells were grown on soft material, they began to function as young cells – in other words, they were rejuvenated. ”
"When we removed Piezo1 from the surface of the old brain cells of the brain, we were able to deceive cells into a soft environment, even when growing on hard material," explained Professor Robin Franklin, who led the research with Dr. Falut. . "What's more, we were able to delete Piezo1 in OPC in old rat brains, leading to cells being rejuvenated and once again able to assume their normal regenerative function."
Dr Suzanne Kohleas, director of research at the MS Association, which funds the research, said: "MS is relentless, painful and disabling, and treatments that can slow down and prevent the accumulation of disability over time are desperately needed. The Cambridge team's findings on how brain cells age and how this process can be modified have important implications for future treatment, as it gives us a new purpose to tackle aging and MS-related problems, including how they are potentially to be done you lost function in the brain. "
This research was supported by the European Research Council, the Association for MS, Biotechnology and Biological Sciences, the Adelson Medical Research Foundation, the Medical Research Council and Welcome.
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