Pro-Longevity Molecules in ‘Young Blood’ Rejuvenate Aged Mouse Muscle

Researchers identify a crucial mediator of youthfulness for mouse muscle in membranous particles circulating the bloodstream, a discovery that could advance muscle regeneration therapies for older people.

From some freaky Frankenstein-like studies where researchers sowed together the blood vessels of young and old mice, allowing blood to exchange between the two rodents, researchers showed that circulating factors play a critical role in regeneration and rejuvenation. Beyond carrying oxygen, nutrients, and hormones to cells while removing waste products, like carbon dioxide, blood carries factors that affect the aging and function of stem cells and tissues, including muscle. While many of these factors have been identified as freely circulating proteins, studies have shown that there are membranous particles secreted from cells called extracellular vesicles (EVs), which traffic between anatomically remote sites and serve as biomolecule couriers.

In a study published in Nature Aging, University of Pittsburgh Medical Center (UPMC) researchers demonstrate that EVs carrying particular genetic material drive the beneficial effect of blood from young mice on aged muscle regeneration. Sahu and colleagues show that EVs containing mRNA encoding the pro-longevity protein α-Klotho (Klotho) can mimic the effects of blood from young mice on aged skeletal muscle. 

“We’re really excited about this research for a couple of reasons,” said senior author Fabrisia Ambrosio, Ph.D., director of rehabilitation for UPMC International and associate professor of physical medicine and rehabilitation at Pitt. “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.”