Aging is the single biggest risk factor for brain disorders like Alzheimer’s, Huntington’s disease, and amyotrophic lateral sclerosis (ALS). But exactly how getting older makes the brain more vulnerable has remained a mystery.
Now, researchers at the University of Cologne have identified a direct molecular link between aging and neurodegeneration, shedding light on why harmful proteins build up in the brain as we age.
The study, published in Nature Aging, was led by Professor Dr. David Vilchez and his team at the CECAD Cluster of Excellence for Aging Research. Using the tiny nematode worm Caenorhabditis elegans—a common model organism for aging studies—the researchers zeroed in on a protein called EPS8.
This protein naturally increases in levels as organisms grow older.
But with that rise comes trouble: EPS8 activates harmful stress responses in cells that shorten lifespan and encourage toxic protein aggregation.
Protein aggregation occurs when misfolded proteins clump together instead of being cleared away.
These clumps are a hallmark of many neurodegenerative diseases and can severely damage nerve cells.
In the worm models of Huntington’s disease and ALS, the Cologne researchers found that high levels of EPS8 sped up this process, leading to neurodegeneration.
Crucially, when the scientists reduced EPS8 activity in the worms, they were able to prevent these toxic clumps from forming. Neurons were preserved, and the animals maintained better brain function.
“We are delighted to uncover a molecular mechanism that could shed light on how aging contributes to diseases like ALS and Huntington’s,” said first author Dr. Seda Koyuncu. “For years, we’ve known that age is the major common risk factor. This study may contribute to filling in part of that puzzle.”
The findings became even more significant when the team tested them in human cells. EPS8 and its associated signaling pathways are evolutionarily conserved, meaning they exist across species, including in people.
Just like in worms, reducing EPS8 levels in human cell models of Huntington’s disease and ALS prevented toxic protein aggregation.
Professor Vilchez emphasized the importance of this discovery: “It’s incredibly exciting that the mechanisms we uncovered in worms are also conserved in human cells. This shows how simple model organisms can help us reveal processes that are deeply relevant to human disease.”
While researchers are still working to understand the exact details of how EPS8 drives protein aggregation, the study identifies a clear molecular connection between aging and neurodegeneration.
Even more promising, it points to EPS8 and its signaling partners as potential targets for new therapies. Treatments that reduce EPS8 activity might slow or even prevent the progression of age-related neurodegenerative diseases.
As the population ages worldwide, the need to understand and treat these conditions grows more urgent. This new discovery brings scientists one step closer to unlocking why age is so closely tied to brain decline—and how we might break that link.
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