Recently, in a research report published in the international journal Nature, scientists from the University of Cambridge have revealed the molecular mechanism of brain stem cell dysfunction caused by the increase of brain stiffness with age, and the researchers have also developed a new method can reverse aging stem cells back to age health status. Relevant findings are expected to help researchers understand the aging process of the brain and how to develop new therapies for age-related brain diseases.
As the body ages, muscles and joints become stiff, which makes daily activities more difficult. This study shows that our brains also suffer these changes, and age-related brain stiffness may have an important impact on the function of brain stem cells. In this study, the researchers studied the brains of young and aging rats to elucidate the effects of age-related brain stiffness on the function of oligodendrocyte progenitor cells (OPCs). OPCs are a class of brain stem cells that are important for maintaining normal brain function. They are also important for the regeneration of myelin, a fatty sheath around nerve tissue, which is often damaged in the case of multiple sclerosis. The effects of aging on these cells often trigger the development of multiple sclerosis, and the function of these cells also declines in aging healthy populations.
In order to determine if functional deficits in aged OPCs could be reversed, the researchers transferred aged OPCs from aged rats to soft, spongy brain tissue in young rats. It is worth noting that these aging brain cells are able to rejuvenate and behave much more like young, strong cells. In this study, researchers developed new materials with variable degrees of stiffness in the laboratory and studied the growth of these materials and their effects on rat brain stem cells in a controlled environment, and these materials can be used to engineer aging brains.
To gain insight into the molecular mechanisms underlying the softness and stiffness of brain tissue affecting cell behavior, the researchers analyzed a protein called Piezo1 that "informs" cells that the surrounding environment is soft or stiff. Researcher Kevin Chalut said that, “We found that when promoting the growth of young rat stem cells on rigid materials, these cells showed dysfunction and lost their ability to regenerate, in fact, behaving like aging cells. When aging brain cells grow on soft materials, their function will behave like young cells, in other words, they can restore youthful vitality.”
When researchers removed the Piezo1 protein from the surface of aging brain stem cells, they can trick cells into sensing the soft surrounding environment, even when growing cells on stiff materials. In addition, when Piezo1 on OPCs is removed from the aging rat brain, it promotes younger cells and assumes normal regeneration. Researcher Susan Kohlhaas said that, “Multiple sclerosis is a painful disease that disabling patients. Over time, we urgently need to develop new therapies that slow and inhibit patient disability.”
In this study, the researchers elucidated the molecular mechanisms of brain stem cell aging and how to restore brain stem cell viability by reversing the process. For further study, the researchers elucidated the molecular mechanisms of brain stem cell aging and how to restore brain stem cell viability by reversing the process.
- Michael Segel, Björn Neumann, Myfanwy F. E. Hill, et al. Niche stiffness underlies the ageing of central nervous system progenitor cells, Nature (2019). DOI: 10.1038/s41586-019-1484-9.