Reactivation of Ageing Brain Stem Cells
Advances in understanding stem cell behaviour
With advancing age or in Alzheimer’s patients, the formation of new neurons steadily decreases, leading to a decline in memory. Over time, stem cells in the brain lose the ability to divide and generate new nerve cells, which affects memory function.
Researchers at the University of Zurich have uncovered a mechanism involved in stem cell ageing and show that the formation of new nerve cells can be reactivated.
Brain stem cells are responsible for the lifelong formation of new nerve cells, for example in the hippocampus, a brain region important for various memory processes. In Alzheimer’s patients or elderly people, the formation of new nerve cells in the hippocampus continuously decreases, which impairs memory performance.
Uneven distribution of age-related cell damage
In a study, the team of Sebastian Jessberger, professor at the Institute of Brain Research at the University of Zurich, investigated how the formation of new nerve cells is impaired. Protein structures in the nucleus of brain stem cells enable the uneven distribution of damaged proteins, which accumulate over time, to the two daughter cells during cell division. This is crucial for stem cells to maintain their ability to divide over long periods of time to ensure the replenishment of neurons. However, with age, the amounts of these nuclear proteins change, leading to a defective distribution of age-related proteins. Therefore, fewer and fewer neurons are formed in the brains of ageing mice.
The nuclear protein lamin B1 is central to this process, as its amount decreases with age. When the researchers experimentally increased the amount of lamin B1 in ageing mice, stem cell division improved and new nerve cell formation increased. “Throughout the body, stem cells gradually lose their ability to divide with age. Using genetic engineering and state-of-the-art microscopy, we were able to identify a mechanism involved,” explains Khadeesh bin Imtiaz, PhD student and lead author of the study.
Stopping the ageing process of stem cells
The research is part of several ongoing projects that aim to reactivate ageing stem cells in the future. Injured tissue generally regenerates more poorly with age, which means that almost all stem cell types in the body are affected.
“Although our study focuses on brain stem cells, similar mechanisms could also play a role in the ageing of other body stem cells”, says Sebastian Jessberger. The new findings represent an important step towards investigating age-related changes in stem cell behaviour in more detail. “We now know that we can activate stem cells in the ageing brain. Our goal is to contribute to increasing the formation of new nerve cells, for example in elderly people or patients with degenerative diseases such as Alzheimer’s disease. Even if this will still take a few years”, Jessberger concludes.
M.K. bin Imtiaz, B.N. Jaeger, S. Bottes, R.A.C. Machado, M. Vidmar, D.L. Moore, S. Jessberger; “Declining lamin B1 expression mediates age-dependent decreases of hippocampal stem cell activity”; Cell Stem Cell; 24 February 2021.