A study by UC Berkeley researchers found that glial cells in roundworm brains prolong their life span by regulating stress responses, which could lead to advances in regulating aging and age-related diseases in humans.
A nervous system’s ability to sense cellular stress is essential for an organism’s health, according to the study. The capacity to respond to this stress and mitigate protein homeostasis, or the correct balance of proteins, deteriorates with age.
The researchers altered the amount of a specific protein in a small number of glial cells, generally understood as support cells for neurons, in roundworms. They discovered that this alteration increased the roundworms’ life span by 75%.
“There is mounting evidence that glial cells play a central role in age-onset diseases like neurodegeneration. Our lab previously showed that neurons play an important role in controlling protein homeostasis for the whole organism,” said campus postdoctoral fellow and primary author of the study Ashley Frakes in an email. “When I joined the Dillin lab, I hypothesized that glial cells must be involved in this maintenance and protection as well.”
In order to determine whether or not glial cells play a role in mitigating protein homeostasis and longevity, researchers generated roundworm strains that overexpressed the protein XBP-1 in a subset of glial cells, according to the study. This protein regulates the cellular stress response.
The study found that the roundworms expressing enhanced levels of XBP-1 showed a “marked increase” in survival compared to their control counterparts. These roundworms were more resistant to protein aggregation and chronic stress.
“One main hallmark of aging and many age-onset diseases is the loss of protein homeostasis,” Frakes said in the email. “Gaining a deeper understanding of this process may eventually help identify specific therapeutic interventions to maintain or rebalance protein homeostasis during aging and age-related disease.”
Glial cells in roundworms are similar to the type of glial cells in the mammalian brain, according to Frakes. She added that because the way glial cells communicate in roundworms is similar in humans, the study suggests that glial cells in humans could work in a similar way as they did for the altered roundworms.
Frakes is currently working to identify the signal that glial cells send to other cells to regulate protein homeostasis and longevity.
If identified, Frakes said they may be able to generate small molecules that could help mimic this response in humans. She added that this could be used for specific therapeutic interventions to rebalance protein homeostasis during aging.
“It is becoming clear that glial cells are becoming more important than the neuroscience community ever appreciated,” Frakes said in an email. “Glia are not just passive bystanders to neurons. They are important mediators of physiological health and lifespan.”
Contact Maria Young and Amanda McNamara at [email protected].