Developmental genes turn on in astrocytes during aging!

Developmental genes turn on in astrocytes during aging!

Potentially explaining why even healthy brains don't function well with age, researchers have discovered that genes that are switched on early in brain development to sever connections between neurons as the brain fine-tunes, are again activated in aging neuronal support cells called astrocytes. The work, which appeared in Cell Reports , suggests that astrocytes may be good therapeutic targets to prevent or reverse the effects of normal aging.

Although not nearly as well studied as neurons, astrocytes--named for their star-shaped appearance--make up one-third to one-half of all the cells in the brain and are increasingly being found to be critical for neuronal function.

Neuroscientists know that in the young, developing brain, synapses are being activated and deactivated, while in the adult brain they are mostly stable. But in aging brains, neurons start to lose connections and don't communicate as well. Researchers wondered whether the changes to synapses and neuronal communication during aging might be related to changes in astrocytes.

To find out, they decided to compare gene expression in astrocytes in the adult brain versus the aged brain in mice. This would give them an idea of which genes are active at the two stages. To develop a comprehensive view of astrocyte gene expression, the duo used the bibo-tag technique in four very different areas of the mouse brain: two regions of the cortex and the hypothalamus and cerebellum.

To their surprise, they found that most of the properties that make an astrocyte an astrocyte didn't change much with age--gene expression was fairly consistent with time. But what did change: genes that during development would normally cause the loss of connections between neurons were switched on again in the aging astrocytes. Aging astrocytes show minimal alteration of homeostatic and neurotransmission-regulating genes. However, aging astrocytes upregulate genes that eliminate synapses and partially resemble reactive astrocytes. Authors further identified heterogeneous expression of synapse-regulating genes between astrocytes from different cortical regions.

"This suggests that there's some sort of genetic program that's being reactivated in these astrocytes as they age that's causing neurons to lose their connections with each other," says the senior author.

Interestingly, the areas in which astrocytes looked the most different were brain areas where neurons are known to function notably less well with age or even to die--the cerebellum and the hypothalamus.

"This may explain why metabolism decreases and coordination gets worse with age, because these are functions that are coordinated by the hypothalamus and cerebellum," adds the graduate student.

The team has made their study data publicly available for other researchers to use. In future, the lab plans to compare aging astrocytes to astrocytes in models of disease to see whether there could be prepathological changes that allow the transition to disease to occur.