Beyond muscles, this could also help reverse other effects of aging such as boosting cognitive performance.
Our muscles gradually shrink, weaken, and lose their ability to heal after damage as we age. In a recent study, researchers from UPMC and the University of Pittsburgh identify a critical modulator of youthfulness in mouse muscle, a discovery that could boost muscle regeneration therapy for the elderly.
The study, which was published today in Nature Aging, shows that circulating shuttles called extracellular vesicles, or EVs, transmit genetic instructions for the longevity protein Klotho to muscle cells. Loss of muscle function and reduced muscle healing in old mice may be caused by aged EVs, which contain fewer copies of these instructions than those found in young animals.
The new research builds on years of scientific research revealing that when aged mice are given blood from young mice, numerous cells and tissues regain their youthful appearance. However, it was previously unknown which components of young blood conferred 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,” says Dr. Amrita Sahu, lead author.
“Like a message in a bottle, EVs deliver information to target cells.”
Dr. Fabrisia Ambrosio, senior author of the study and her colleagues took serum from young mice and put it into aged mice with wounded muscle. Serum is the fraction of blood that remains after eliminating blood cells and clotting components. Mice given young serum had better muscle regeneration and functional recovery than mice given a placebo, but the serum’s restorative properties were lost when the EVs were removed, showing that these vesicles mediate the therapeutic benefits of young blood.
Further investigation revealed that EVs transmit genetic instructions, or mRNA, encoding the anti-aging protein Klotho to muscle progenitor cells, a type of stem cell necessary for skeletal muscle regeneration. EVs from aged mice contained fewer copies of the Klotho instructions than those from young mice, causing muscle progenitor cells to manufacture less of this protein.
With increasing age, muscle doesn’t heal as well after damage because scar tissue is deposited instead of restoring original muscle structure. In earlier work, Ambrosio and her team showed that Klotho is an important regulator of regenerative capacity in muscle progenitor cells and that this protein declines with age.
For the first time, the new work indicates that age-related changes in EV cargo lead to Klotho depletion in old stem cells, implying that EVs could be transformed into innovative therapeutics for repairing injured muscle tissue.
“EVs may be beneficial for boosting regenerative capacity of muscle in older individuals and improving functional recovery after an injury,” adds Ambrosio.
“One of the ideas we’re really excited about is engineering EVs with specific cargoes, so that we can dictate the responses of target cells.”
Aside from muscles, EVs may be useful in reversing other aging effects. Previous research has shown that fresh blood can improve the cognitive performance of older rats.
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