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Why people’s sense of smell deteriorates with age

As we age, we begin to lose our sense of smell, and we can’t always pick up on odors as strongly as we could in our youth. This is something that all mammals experience as part of the aging process, but until now, it was not well-understood why.

Researchers from the Helmholtz Zentrum München and the University Medical Centre Mainz set out to figure out what underlying mechanisms cause mammals to lose some of their sense of smell. The researchers conducted a study examining olfactory neurons and tracking stem cell development in mice.

The development of new neurons in the brain is called neurogenesis and mainly happens during early childhood. However, some regions experience several stages of neurogenesis including olfactory neurons.

“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,” said Carsten Marr, a co-author of the study which was published in the journal Cell Reports.

The researchers examined stem cell development in the olfactory region of the brain in mice and used confetti reporters to track the stem cell development.

Confetti reporters trace stem cells and their descendants using different fluorescent colors to highlight which cells belong to which lineage.

“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,” said Filippo Calzolari. “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.”

After the researchers traced the lineages of stem cells in the mice, the resulting data from the confetti reporting process was so varied and mixed that it was impossible to perform a systematic analysis of the data to compare young and old mice brains.

To resolve this problem, a team of mathematicians and specialists in the quantification of single-cell dynamics developed mathematical models and algorithms using artificial intelligence to help analyze the data.

“We compared the confetti measurements with several mathematical models of neurogenesis,” said Lisa Bast, the lead author of the study. “We found that the ability of self-renewal declines in old age, especially in certain intermediate stages called transit amplifying progenitors.”

The mathematical models also showed that stem cell division increases but does not impact olfactory cells, rather asymmetric cell division increases.

“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,” said Jovica Ninkovic, a member of the research team.

Not only do the results of the study help explain why sense of smell deteriorates in old age, but it’s also the first study of its kind that successfully uses a mathematical model to describe stem cells and quantify neural stem cells in the brains of living mammals.

By Kay Vandette, Staff Writer

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