Greater Levels of Dbx2 Appear Connected to Neural Stem Cell Decline in Aging

Stem cells are responsible for tissue maintenance, delivering replacement somatic cells and a variety of signals that help to keep organs and other biological systems running. There are many varieties of stem cell, at least one for every tissue type, and all have significant differences in their biochemistry. Unfortunately, one of the shared behaviors in all stem cell populations is a slowing of activity with advancing age, an evolved response to rising levels of damage in cells and tissues that probably serves to reduce the risk of cancer, but at the cost of a decline into organ failure, as essential maintenance shuts down.

The research here is characteristic of a wide range of initiatives that seek to find signal and regulator proteins that can override the evolved reduction in stem cell activity. The aim is to increase activity to youthful levels, and thus avoid the slowdown. Evidence from stem cell therapies and a variety of other approaches to regenerative medicine suggest that this will not cause as great a risk of cancer as feared, even though it doesn't address the underlying damage in cells. Forcing damaged cells in a damaged environment into greater activity must have adverse consequences at some point, but it seems there is nonetheless some leeway to do just that within the present natural state of stem cell aging.

Cells in the brain are constantly dying and being replaced with new ones produced by brain stem cells. As we age, it becomes harder for these stem cells to produce new brain cells and so the brain slowly deteriorates. By comparing the genetic activity in brain cells from old and young mice, the scientists identified over 250 genes that changed their level of activity with age. Older cells turn on some genes, including Dbx2, and they turn off other genes.

By increasing the activity of Dbx2 in young brain stem cells, the team were able to make them behave more like older cells. Changes to the activity of this one gene slowed the growth of brain stem cells. These prematurely aged stem cells are not the same as old stem cells but have many key similarities. This means that many of the genes identified in this study are likely to have important roles in brain ageing.

The research also identified changes in several epigenetic marks - a type of genetic switch - in the older stem cells that might contribute to their deterioration with age. Epigenetic marks are chemical tags attached to the genome that affect the activity of certain genes. The placement of these marks in the genome change as we age and this alters how the cells behave. The researchers think that some of these changes that happen in the brain may alter causing brain stem cells to grow more slowly. "We hope this research will lead to benefits for human health. We have succeeded in accelerating parts of the ageing process in neural stem cells. By studying these genes more closely, we now plan to try turning back the clock for older cells. If we can do this in mice, then the same thing could also be possible for humans."

Link: https://www.babraham.ac.uk/news/2018/03/genes-for-agelinked-brain-deterioration-identified

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