- Brain deteriorates with age because stem cells produce new brain cells more slowly.
- Changes to the activity of a group of around 250 genes cause brain stem cells to slow down.
- Young stem cells behave like older ones if the activity of the Dbx2 gene is increased.
A group of around 250 genes involved in age-related brain deterioration has been identified by scientists at the Babraham Institute, Cambridge and Sapienza University, Rome. The research finds that changes to one of these genes, called Dbx2, could prematurely age brain stem cells, causing them to grow more slowly.
Dbx2 gene and 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 some genes, including Dbx2, on and they turn other genes off.
By increasing the activity of Dbx2 in young brain stem cells, the team was 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 aging.
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.
First author on the paper, Dr Giuseppe Lupo, Assistant Professor at Sapienza University said: "The genes and gene regulators that we identified are corrupted in neural stem cells from older mice. By studying the Dbx2 gene we have shown that these changes may contribute to aging in the brain by slowing the growth of brain stem cells and by switching on the activity of other age-associated genes."
Co-lead scientist Dr Peter Rugg-Gunn at the Babraham Institute said: "Aging ultimately affects all of us and the societal and healthcare burden of neurodegenerative diseases is enormous. By understanding how aging affects the brain, at least in mice, we hope to identify ways to spot neural stem cell decline. Eventually, we may find ways to slow or even reverse brain deterioration - potentially by resetting the epigenetic switches - helping more of us to stay mentally agile for longer into old age."
Co-lead scientist Dr Emanuele Cacci at Sapienza University said: "We hope this research will lead to benefits for human health. We have succeeded in accelerating parts of the aging 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."
- Giuseppe Lupo, Paola S. Nisi et al. Molecular Profiling of Aged Neural Progenitors Identifies Dbx2 as a Candidate Regulator of Age-associated Neurogenic Decline, Aging Cell DOI: 10.1111/acel.12745
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