How Aging Reduces Neurogenesis In The Hippocampus And Increases The Risk Of Dementia

Hippocampus (Credit: psychologytoday.com)

We all know that as we get older, our minds start to get a little fuzzy. For an increasing number of us, however, cognitive decline and dementia dramatically affect our ability to function normally as we age. The hippocampus is a region of the brain important for memory and cognition. Interestingly, or perhaps crucially, the hippocampus is also one of only two brain regions which continue to create new neurons throughout adult life. This is a process we know as neurogenesis.

Stem cells reside within the hippocampus in an area known as the dentate gyrus. Under the appropriate physiological conditions, these stem cells rapidly proliferate and differentiate into fully functioning neurons. Carbon dating studies suggest that adult humans produce around 700 new neurons a day, which is thought to contribute to hippocampus-based cognitive tasks such as spatial navigation and pattern separation (separating similar events, situations or objects into distinct memories).

While the technology to visualize neurogenesis in the living human doesn’t yet exist, in human post-mortem studies we see a marked decline in neurogenesis in Alzheimer’s disease. We likewise see a decline in neurogenesis in Parkinson’s disease and normal brain aging, both of which are associated with an increased risk of cognitive impairment and dementia. Rodent studies have similarly seen declining cognitive ability in mice that have reduced neurogenesis, as well as improved cognitive ability in mice in which neurogenesis is boosted via exercise or social interaction. The evidence is convincing, therefore, that neurogenesis and cognitive ability are closely linked.

So if hippocampal neurogenesis is a normal physiological process in adults, why is it that it declines in old age? Are our stem cells being used up over time until there are none left, or are there pathological changes in our brains which prevent them from becoming new neurons? While opinion remains divided amongst rodent researchers, studies in human tissue have been unable to shed light on this problem. However, a recent study by Mathews et.al, published in Aging Cell, is beginning to help us understand what might be happening to our hippocampus as we get older.

Using polymerase chain reaction (PCR) the study analyzed genes that are expressed during different stages of neurogenesis, particularly focusing on stem cells, proliferating cells, neuronal precursor cells and immature neurons. Genes specific to proliferating cells and immature neurons declined consistently with age, consistent with previous studies in human and rodent tissue. However, the genes specific to stem cells and to neuronal precursors did not decline throughout adult life. This may be an indication that while proliferation and maturation of new neurons decline with normal aging, this is not due to stem cells being depleted but instead specific physiological changes that target those two particular stages of neurogenesis. Further statistical analysis revealed that the resulting declines in cell proliferation and maturation may be the result of not one, but two separate physiological changes.

The results of this study are promising as they reveal for the first time that the human hippocampus may maintain a consistent supply of stem cells in the hippocampus, but these cells are becoming increasingly dormant as we age. They key is to find out how we go about reactivating these stem cells so that they can continue contributing to our cognitive processes. With a host of studies already investigating the effect of exercise, social interaction, blood flow and diet on neurogenesis (for a start!), it is only a matter of time before we can begin to reclaim our memory and finally make dementia a thing of the past.

This study, Evidence for reduced neurogenesis in the aging human hippocampus despite stable stem cell markers was recently published by Mathews KJ, Allen KM, Boerrigter D, Ball H, Shannon Weickert C, and Double KL in the journal Aging Cell.

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