Extracellular Vesicles: Key to Halting Aging?

Researchers at the College of Veterinary Medicine (CVM) are a step closer to finding the fountain of youth.

In a study published Oct. 14 in the Journal of Biological Chemistry, scientists have outlined exactly how embryonic stem cells (ESCs) protect other cells from the effects of oxidative stress, thus preventing cellular aging.

"It was almost like harnessing the power of youth," said first author Shun Enomoto, doctoral student in biochemistry, molecular and cell biology in the lab of Richard Cerione, Distinguished Professor of Arts and Science in Chemistry (CVM).

That power comes from tiny sacs, called extracellular vesicles, secreted by the ESCs. Previous research had shown that these vesicles could help stem cells maintain their unique characteristics, sparking research by other groups to prove that the vesicles also could be used to promote wound healing and tissue regeneration.

"The question we were next interested in," Enomoto said, "was whether these extracellular vesicles could not only help cells regenerate but also delay or stop their aging."

To do this, Enomoto and his collaborators, including Cerione and Marc Antonyak, associate research professor in the Department of Molecular Medicine (CVM), isolated the vesicles from mouse embryonic stem cells and added them to petri dishes containing differentiated (non-stem) cells. What happened next astonished them: Cells treated with the vesicles completely avoided senescence - a hallmark of aging where cells stop dividing and working properly.

"It was an amazing thing to watch these treated cells just continue to grow long after the untreated ones had stopped," Antonyak said.

The team dug deeper, running experiments to elucidate the protein signaling pathway behind the vesicle's anti-aging. It starts, Enomoto said, with the extracellular matrix protein fibronectin, which coats the surface of the vesicles.

Fibronectin latches onto the surface of cells and triggers a cascade of enzymes, including FAK and AKT, that block the effects of oxidative stress that would otherwise trigger cells to undergo senescence, Enomoto said.

Pinpointing this protein pathway is vital information, Cerione said. "The more you understand around the aging process," he said, "the more insightful strategies you have to combat that process."

The team plans to further explore the power of embryonic stem cell vesicles. "Our ultimate goal is to test these vesicles directly in mice to see if they affect the organism's aging," Enomoto said.

If that proves successful, the team will investigate the properties using human cells - a key caveat being that all human embryonic stem cells would be created from regular adult cells that have been genetically reprogrammed to revert to an embryonic-like state.

"It's not just about increasing lifespan, but increasing the length of time you can expect to be healthy," Antonyak said. "This work could have a lot of important applications for human health."

Lauren Cahoon Roberts is director of communications for the College of Veterinary Medicine.

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