By harvesting cells from mice of varying ages and culturing them within the organoid model, the researchers were able to observe the aging process in real-time. They found a clear and measurable decline in the ability of cells from older mice to generate new neurons compared to those from younger counterparts.
"We found a decline in the ability of the older mice cells to generate new neurons," says Lin. "We think this is due to a decrease in the GBC population as we age, but we need to do more work to test this hypothesis and if so, develop ways to rejuvenate them."
The implications of this finding are significant. If the loss of smell in the elderly is tied specifically to the depletion or exhaustion of the GBC population, it opens the door for targeted regenerative therapies. By understanding the signals that HBCs use to support GBCs, scientists may eventually be able to develop interventions that "reboot" the regenerative process in older adults, potentially restoring a sense of smell that was previously thought to be lost forever.
An Easy-To-Use Model
One of the most significant achievements of this study is not just the biological discovery itself, but the tool used to reach it. The lead author of the study, Juliana Gutschow Gameiro, joined the Tufts team as a visiting Ph.D. student from the State University of Londrina in Brazil. Her mission was to create a model that was not only scientifically rigorous but also accessible.
In many high-level biological studies, the equipment and specialized reagents required to grow complex tissue models can be prohibitively expensive, limiting the research to a handful of well-funded institutions. Gameiro and Lin were determined to change that, designing a 3D olfactory organoid that is relatively easy to create even in labs with limited funds and specialized equipment.
"Because loss of smell is associated with COVID-19, as well as with Parkinson’s disease and other conditions, a much larger number of researchers from a variety of different fields have begun researching olfactory epithelial cells in the last few years," says Lin.
The sudden global focus on anosmia—the total loss of smell—due to the COVID-19 pandemic created an urgent need for better research tools. By providing an easy-to-use model, the Tufts team is essentially democratizing the study of the nose. They hope that by lowering the barrier to entry, researchers specializing in neurology, virology, and gerontology can use the model to explore how different diseases and environmental factors impact the olfactory system.
"We wanted to develop an easy-to-use model so that non-stem cell biologists and those working in labs with limited resources could use it to better understand how olfactory neurons regenerate and what happens that causes that process to diminish or fail completely," Lin says.
