The Supply of New Olfactory Neurons Diminishes with Age

Stem cell populations maintain tissues in large part by providing a supply of new daughter cells to replace losses and repair damage. This supply diminishes with age, however, as stem cell populations become ever less active. This results from some mix of damage to the stem cells themselves and the more general damage of aging, accompanied by altered signaling as a reaction to that damage. The consensus is that stem cells have evolved to become less active in a damaged environment in order to diminish risk of cancer, but this is by no means settled, given that various approaches to force stem cells into greater activity appear to cause far less cancer than expected.

The decline in stem cell function is perhaps best studied in muscle tissue, but the phenomenon is most likely present in all tissues, each supported by its own varieties of stem cell. Here, researchers painstakingly demonstrate that neural stem cells falter in their delivery of olfactory neurons. The necessary functional tissue will thus deteriorate, and this contributes to the failing sense of smell observed in older individuals.

In mammals, generation of new neurons (neurogenesis) is mainly limited to early childhood and occurs in adulthood only in a few regions of the forebrain. One such exception is olfactory neurons, which develop from stem cells via several intermediate stages. "The production of these neurons diminishes with advancing age. In our recent study we wanted to find out the cellular basis and what role stem cells play in the process. Our approach utilised what are known as confetti reporters to perform lineage tracing: In mouse brains, we induced individual stem cells and all their descendants - called clones - to light up in a specific colour. In this way, we could distinguish clones over time by the different colours."

"In the next step, we compared clones found in young and older mice to find out what contribution individual stem cells and intermediates make to the neurogenesis of mature olfactory cells. We compared the confetti measurements with several mathematical models of neurogenesis. We found that the ability of self-renewal declines in old age, especially in certain intermediate stages called transit amplifying progenitors. In addition, analysis showed that asymmetric cell division and quiescence of stem cells increased in older mice. That means that fewer cells differentiate into olfactory cells in old age as they tend to remain in the stem cell pool and become less active. Therefore, the production comes to a halt."



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