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," says the senior author.
"Our approach utilized 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 color", says one of the authors. In this way, the scientists could distinguish clones over time by the different colours that give the technique its name. "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", another author adds.
However, systematic analysis of these images proved nearly impossible for humans, in that the available data were extremely heterogeneous, making a comparison of young and old brains difficult.
"We compared the confetti measurements with several mathematical models of neurogenesis," explains another author. "We found that the ability of self-renewal declines in old age, especially in certain intermediate stages called transit amplifying progenitors." In addition, the 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", says the author. The work is the first in which scientists have been able to quantitatively describe the behavior of neural stem cells in the living mammalian brain using a mathematical model.
Why our sense of smell declines in old age
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