Why our brains produce fewer new neurons in old age

August, 2011

New research explains why fewer new brain cells are created in the hippocampus as we get older.

It wasn’t so long ago we believed that only young brains could make neurons, that once a brain was fully matured all it could do was increase its connections. Then we found out adult brains could make new neurons too (but only in a couple of regions, albeit critical ones). Now we know that neurogenesis in the hippocampus is vital for some operations, and that the production of new neurons declines with age (leading to the idea that the reduction in neurogenesis may be one reason for age-related cognitive decline).

What we didn’t know is why this happens. A new study, using mice genetically engineered so that different classes of brain cells light up in different colors, has now revealed the life cycle of stem cells in the brain.

Adult stem cells differentiate into progenitor cells that ultimately give rise to mature neurons. It had been thought that the stem cell population remained stable, but that these stem cells gradually lose their ability to produce neurons. However, the mouse study reveals that during the mouse's life span, the number of brain stem cells decreased 100-fold. Although the rate of this decrease actually slows with age, and the output per cell (the number of progenitor cells each stem cell produces) increases, nevertheless the pool of stem cells is dramatically reduced over time.

The reason this happens (and why it wasn’t what we expected) is explained in a computational model developed from the data. It seems that stem cells in the brain differ from other stem cells. Adult stem cells in the brain wait patiently for a long time until they are activated. They then undergo a series of rapid divisions that give rise to progeny that differentiate into neurons, before ‘retiring’ to become astrocytes. What this means is that, unlike blood or gut stem cells (that renew themselves many times), brain stem cells are only used once.

This raises a somewhat worrying question: if we encourage neurogenesis (e.g. by exercise or drugs), are we simply using up stem cells prematurely? The researchers suggest the answer depends on how the neurogenesis has been induced. Parkinson's disease and traumatic brain injury, for example, activate stem cells directly, and so may reduce the stem cell population. However, interventions such as exercise stimulate the progenitor cells, not the stem cells themselves.

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