How Stress-Response Genes Aid in Clearing Dead Cells

A new study from The University of Texas at Arlington reveals an unexpected role for stress-response genes in the body’s process of clearing out dead cells, a finding that could shed light on diseases involving the immune system, brain, and metabolism.

According to Aladin Elkhalil, lead author of the study published in PLOS Genetics, “The body is constantly creating new cells and removing old cells once they die. This removal of dead cells is just as important as creating new ones, because if the body is unable to rid itself of dead cells, it can lead to various health problems.”

The research team leveraged C. elegans’ unique features to explore how stress-response genes, many with human equivalents, assist in removing dying cells. “This has been an exciting study, where stress meets cell behavior,” said senior author Piya Ghose. “It’s fascinating to see how our cells adapt to changes in their surroundings and still perform their normal functions. Understanding that process is essential to our normal physiology and development.”

By using CRISPR/Cas9 gene-editing and advanced live imaging, the researchers identified a specific stress-response pathway that activates during cell clearance. They observed the timing and activation of both stress-related and clearance genes as dead cells were removed. Notably, the study highlighted a key gene whose human counterpart, lyst, is associated with Chediak-Higashi Syndrome—a rare disorder where the body struggles to clear cellular debris, leading to immune issues.

“One of the novel findings in our study is that the worm version of this gene is controlled by classical stress-response genes, which was previously unknown,” Elkhalil said. “An intriguing question is why this pathway needs to be in place at all. That leaves us with an exciting avenue for future research.”