Confetti in the head Why the smelling ability diminishes in old age

Stem cell research: Why people can smell worse in old age

In mammals such as humans, smelling ability decreases with age. Researchers have now investigated why this is so. For the analysis, the scientists followed the stem cell development in the brain of mice with so-called confetti reporters.

Disturbances of the sense of smell affect the quality of life

A few years ago researchers from the USA reported on their study, according to which the nose not only perceives 10,000 different odors, but also about one trillion (1,000,000,000,000) odors. However, if the olfactory cells do not work properly, you will lose a lot of quality of life. Disorders of the sense of smell mean a massive restriction in the everyday life of those affected. But as you grow older, your sense of smell in humans - as in other mammals - decreases. Why this is so, has examined an interdisciplinary research team from Helmholtz Zentrum München and the University of Mainz in the journal "Cell Reports".

As you grow older, your sense of smell diminishes. Researchers have now investigated why this is so. (Photo: Halfpoint / fotolia.com)

Stem cell-derived olfactory nerves

In mammals, the formation of nerve cells (neurogenesis) is mainly limited to early childhood and takes place in adulthood only in a few regions of the forebrain.

One such exception is olfactory nerves, which emerge from several intermediate stages of stem cells.

"The production of these nerve cells is running out with increasing age," explains the head of the working group at the Institute of Computational Biology (ICB) of Helmholtz Zentrum München, Dr. med. Carsten Marr, in a message.

"We wanted to clarify in the current work, how it comes to it and what contribution the stem cells have," said the scientist.

Confetti reporter

To investigate this question, Dr. Marr with mathematician Lisa Bast and stem cell researchers Filippo Calzolari (today at the Institute of Physiological Chemistry of the University Medical Center Mainz) and Prof. Dr. med. Jovica Ninkovic an interdisciplinary team of experts.

"Our approach to the current work works through so-called confetti reporters in mice: We bring individual stem cells and all their progeny - so-called clones - to shine in a particular color," explains Dr. med. Calzolari.

In this way, the researchers were able to track the development of individual clones and differentiate as different colored dots, which gives the process its name.

"By comparing young and older mice, we wanted to find out in the next step what contribution individual stem cells and intermediates make to the neurogenesis of the finished olfactory cells," continues Calzolari.

In old age, fewer cells develop into olfactory cells

However, the systematic evaluation of the images is hardly manageable for humans: the available data were extremely heterogeneous and a comparison of young and old brains difficult.

Here came the expertise of Dr. Ing. Marr and his team to bear. They are specialists in the quantification of single-cell dynamics, ie the question: Which and how many cells of a large association develop further??

To do this, the scientists make use of artificial intelligence, design mathematical models and program algorithms that can evaluate the image data for them.

"We compared the confetti measurements with several mathematical models of neurogenesis," explains Lisa Bast.

"In this way, we found that especially in certain intermediate stages - the so-called transit amplifying progenitors - the ability to self-renewal decreases in old age."

In addition, the analysis shows that so-called asymmetric cell division in stem cells and their resting phases increased in older mice.

"This means that as we age, fewer cells develop into olfactory cells and remain inactive in the stem cell pool, which stops production," says Jovica Ninkovic.

The work is the first to allow researchers to quantitatively study the behavior of nerve stem cells in the living mammalian brain using a mathematical model. (Ad)