Researchers from the Babraham Institute, Cambridge and Sapienza University, Rome, have been discovered a group of genes and genetic switches associated with age-related brain deterioration. The results of the work, published on March 5, 2018 in Aging Cell, demonstrate that a changes to one of these genes, called Dbx2, could prematurely age brain stem cells, slowing their growth.
Neurons in the brain are constantly dying and being replaced with new ones produced by brain stem cells (SCs). As we age, it becomes harder for SCs to produce new brain cells and so the brain slowly deteriorates.
By comparing the genetic activity of genes in brain cells from young and old mice, scientists identified more than 250 genes, in which the level of activity changed with age. “Old” cells turn some genes, for example, Dbx2, on and they turn other genes off.
By increasing the activity of Dbx2 in young SCs of the brain, the team of scientists was able to make them behave more like older cells. Changes to the activity of just one gene slowed the growth of brain stem cells, and their characteristics were not completely identical to the old SC, but had many key similarities with them.
Scientists have come to the conclusion that many of the genes identified by them in this study are likely to have an important role in brain ageing.
The international team also discovered changes in several epigenetic markers (one of the types of genetic switch) in old stem cells that might contribute to their functional deterioration with age.
Epigenetic marks are chemical tags linked with the genome that affect the activity of certain genes. The location of these marks in the genome varies with age, and this alters how the cells behave. The scientists believe that some of these changes 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 ageing 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: “Ageing ultimately affects all of us and the societal and healthcare burden of neurodegenerative diseases is enormous. By understanding how ageing 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 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.”