Extracellular Vesicles Have Critical Role in Muscle Regeneration

UPMC and University of Pittsburgh researchers have identified what they say is an important mediator of youthfulness in mouse muscle. Their study, published today in Nature Aging, demonstrates that extracellular vesicles ( EVs) deliver genetic instructions for the longevity protein known as Klotho to muscle cells. Loss of muscle function and impaired muscle repair in old mice may be driven by aged EVs, which carry fewer copies of these instructions than those in young animals.

“We’re really excited about this research for a couple of reasons,” said senior author Fabrisia Ambrosio. “In one way, it helps us understand the basic biology of how muscle regeneration works and how it fails to work as we age. Then, taking that information to the next step, we can think about using extracellular vesicles as therapeutics to counteract these age-related defects.”

The new study builds on decades of research showing that when old mice are given blood from young mice, youthful features are restored to many cells and tissues. But until now, it was unclear which components of young blood confer these rejuvenating effects. “We wondered if extracellular vesicles might contribute to muscle regeneration because these couriers travel between cells via the blood and other bodily fluids,” said lead author Amrita Sahu. “Like a message in a bottle, EVs deliver information to target cells.”

Ambrosio and her team collected serum from young mice and injected it into aged mice with injured muscle. Mice that received young serum showed enhanced muscle regeneration and functional recovery compared to those that received a placebo treatment, but the serum’s restorative properties were lost when EVs were removed, indicating that these vesicles mediate the beneficial effects of young blood.

Delving deeper, the researchers found that EVs deliver mRNA encoding the anti-aging protein Klotho to muscle progenitor cells. EVs collected from old mice carried fewer copies of the instructions for Klotho than those from young mice, prompting muscle progenitor cells to produce less of this protein.