It is only recently (the last decade or so) that neuroscientists have realized that the brain harbors a reservoir of neural stem cells, even into adulthood, waiting to be recruited to make new connections. This is an important part of neural plasticity and learning. Now that we know the stem cells are there, research is underway to learn as much about them as possible, including their regulation. Perhaps they play a role in certain diseases, like Alzheimers. Or perhaps they could be exploited to treat or prevent such diseases.

It has also been learned that not all brains are the same in terms of aging. Most brains atrophy and develop pathological signs of aging, and this correlates with a reduction in mental agility (especially the ability to learn new things). But a lucky few do not seem to develop these age-related changes, and can remain mentally nimble well past 100. Nailing down the environmental and genetic variables that make the difference would be interesting and potentially very useful.

For now we are at the basic science level in addressing these questions – just figuring out what is going on. Clinical applications will hopefully come later. But there is one thing it seems we can say now based upon existing research – exercise, both physical and mental, is good for the brain and staves off the negative effects of aging.

A newly published study looking at the regulation of neural stem cells may ultimately illuminate one mechanism behind this. Researchers at the Salk Institute have been studying the regulation of neural stem cells. These are stem cells that lie quietly in the brain, waiting until they are called for to differentiate into neurons and make new connections. This is a delicate balance, however, as these cells need to remain viable and survive for a long time, but not activate or reproduce too much. The researchers have identified one major molecular signal involved in this regulation – the bone morphogenetic factor protein (BMP). They studied its activity in the hippocampus, a brain region involved in memory and clearly shown to harbor neural stem cells.

In a series of experiments they identified that BMP signaling was inactive in proliferating or dividing cells. BMP signaling was active, however, in the quiet neural stem cells. They therefore hypothesized that BMP signaling is at least part of what is keeping these stem cells from dividing – a necessary function in keeping them viable as stem cells for years, while also preventing tumors from growing.

But so far they have only correlated BMP activity with the inhibition of dividing and proliferating. Scientists understand that correlation is not sufficient to establish causation, so they did the typical follow up experiment – they blocked BMP signaling (with a protein called NOGGIN) and showed that this does indeed allow neural stem cells to being dividing. They did this experiment in vitro (in a dish) and in mice brains. They also found that when neural stem cells were allowed to proliferate and turn into neurons, the pool of stem cells was eventually depleted. This suggests that BMP keeping neural stem cells quiet is important to maintaining a pool of stem cells throughout life.

This is an important step in understanding neural stem cells, but is just the beginning in a long path to hopefully understanding the genetic and environmental factors that influence neural stem cell function. It’s always difficult to extrapolate from this kind of basic science to clinical applications – you never know what applications will emerge. News reports tend to jump on the most dramatic potential applications – like preventing the aging of the brain. More often than not this just creates misleading expectations and disappointment (like the recent articles wondering why we haven’t reaped all the promised benefits of the human genome project). To some extent we have to be content to just advance our basic science understanding of the world, knowing that specific applications will spin off eventually, but unpredictably.

Meanwhile there is something everyone can do to improve their aging brain – exercise. It’s simple, but it works.