In research which was published in the journal Nature this week, scientists revealed results which they say have far-reaching implications for the way that we understand how the brain ages and how we may be able to develop therapies for age-related brain diseases.
The research deals with the stem cell dysfunctions that occur as a result of increasing brain stiffness due to age. According to the researchers, it also reveals novel methods for making older stem cells younger and healthier.
Most people are aware of the changes that happen in joints and muscle with aging. Bones can get weaker, muscles less pliant and joints get stiffer and less mobile. This can make everyday activities more challenging and sometimes painful. According to this study, our brains experience a similar change with age. This stiffening strongly impacts the function of brain stem cells.
The research team that executed the research was a multi-disciplinary one based at the Wellcome-MRC Cambridge Stem Cell Institute at the University of Cambridge in Great Britain. They studied the brains of both young and old rats in order to evaluate and understand how age-related brain stiffening affects the function of a specific type of brain cell called oligodendrocyte progenitor cells, or OPCs.
OPCs are a subtype of glial cells. They make up 3-4% of grey matter and 8-9% of white matter. This makes them the 4th most prevalent type of glial cell, after astrocytes, microglia and oligodendrocytes.
OPCs are critical for the maintenance of normal brain function. They play an important role in the regeneration of myelin, which is the fatty sheath surrounding nerves. Myelin is damaged by Multiple Sclerosis (MS,) but the effects of aging on the function of myelin sheaths are experienced both by those with MS and healthy people. Understanding the relationship between age and OPC function, then, may open some important and previously unavailable avenues for treatment of MS and age-related neurodegeneration.
Researchers tested the possibility that age-related function loss in older OPCs was reversible by transplanting OPCs from older rats into the softer, spongier brains of younger ones. They were surprised to find that the older OPCs began to function more like the younger, more robust cells of the younger animals, apparently having been rejuvenated.
The research team also used new materials they developed in the lab for their specific purpose. The materials, of varying stiffness, allowed them to grow and examine rat brain cells in a controlled environment. But in order to more fully understand the ways in which the degree of stiffness of pliability of brain tissue affects OPCs, they had to get a little more specific.
Piezo1 was the thing into which they had to dig deeper. A protein found on the cell surface, Piezo1 communicates the condition of the surrounding environment – is it soft and pliable (young) or stiff (old?)
Co-leader of the research team Dr. Kevin Chalut 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.”
“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,” explained Professor Robin Franklin, who co-led the research with Dr Chalut. “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, 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 aging and MS, including how to potentially regain lost function in the brain.”
By revealing new and exciting details about how brain stem cells age and how they might be rejuvenated, the rats in this experiment may well be showing us how to keep our brains young. More exciting is the possibility of finding new and more effective treatments for debilitating neurodegenerative and age-related disease like MS, Alzheimers and others.
Someone should give those rats a nice big piece of cheese. Not too stiff, though.
This research was supported by the European Research Council, MS Society, Biotechnology and Biological Sciences Research Council, The Adelson Medical Research Foundation, Medical Research Council and Wellcome.
Keep the faith and keep after it!
Journal Reference – Michael Segel, Björn Neumann, Myfanwy F. E. Hill, Isabell P. Weber, Carlo Viscomi, Chao Zhao, Adam Young, Chibeza C. Agley, Amelia J. Thompson, Ginez A. Gonzalez, Amar Sharma, Steffan Holmqvist, David H. Rowitch, Kristian Franze, Robin J. M. Franklin, Kevin J. Chalut. Niche stiffness underlies the ageing of central nervous system progenitor cells. Nature, 2019