More Than 250 Age-linked Brain Deterioration Genes Identified

A group of genes and genetic switches involved in age-related brain deterioration have been identified in research from the Babraham Institute, Cambridge and Sapienza University, Rome. The work found that changes to one of these genes, called Dbx2, could prematurely age brain stem cells, causing them to grow more slowly.

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.

Important Roles In Brain Ageing

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.

neurospheres

Stem cells from the brains of old an young mice grown into balls of cells called neurospheres. The slower growth of cells from older mice produces smaller spheres (lower image).
Credit: Dr. Giuseppe Lupo

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.

Neural Stem Cell Corruption

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.”

Lupo G, Nisi PS, Esteve P, et al.
Molecular profiling of aged neural progenitors identifies Dbx2 as a candidate regulator of age-associated neurogenic decline
Aging Cell. 2018;e12745. https://doi.org/10.1111/acel.12745

Top Image: Dr. Giuseppe Lupo