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Can Young Blood Really Rejuvenate? Its Extracellular Vesicles are the Key

As we age, our muscles gradually become smaller and weaker, and our ability to heal after injury becomes worse and worse. What is the reason behind this?
On December 7, 2021, researchers from the University of Pittsburgh in the United States published a research paper titled Regulation of aged skeletal muscle regeneration by circulating extracellular vesicles in the Nature Aging.
The study found that the decline in muscle function and impaired muscle repair in elderly mice may be driven by extracellular vesicles (EV).
Extracellular vesicles (EV) deliver the mRNA of a longevity protein called Klotho to muscle cells, thereby promoting the regeneration and repair of muscle cells. However, the mRNA of Klotho protein of extracellular vesicles (EV) in aging blood is significantly decreased, which explains why the ability of muscle regeneration decreases with age.
These findings indicate that extracellular vesicles (EV) mediate the beneficial effects of young blood, suggesting that we can use them as therapeutic drugs to counteract the functional defects caused by aging.
The research leader, Dr. Fabrisia Ambrosio of the University of Pittsburgh, said these findings are very exciting and help us understand the biological mechanisms of muscle regeneration and how muscles weaken with age. More importantly, these findings suggest that we can use extracellular vesicles as therapeutic drugs to counteract the functional defects caused by aging.
The new study builds on decades of research that has shown that many cells and tissues return to their youthful state when aging animals are replaced with blood from younger animals, but there has been debate about what in the blood is responsible for the effect.
Extracellular vesicles (EV) refer to vesicle-like bodies with a double-layer membrane structure that are shed from the cell membrane or secreted by the cell, with diameters ranging from 40nm to 1000nm. Extracellular vesicles are mainly composed of microvesicles (MV) and exosomes. Extracellular vesicles are widely present in various body fluids, carrying a variety of cell-derived proteins, lipids, DNA, mRNA, miRNA and so on, and participating in intercellular communication, cell migration, angiogenesis, immune regulation and other processes.
Considering that extracellular vesicles (EV) shuttle between blood and other tissues, and they carry a large amount of information including nucleic acids and proteins, they can also transmit this information to target cells and tissues. Therefore, the research team began to investigate whether extracellular vesicles (EV) contribute to muscle regeneration.
The research team collected serum from young mice, then removed blood cells and clotting factors, and injected the remaining blood into old mice with muscle injuries. Compared with older mice that received placebo treatment, mice that received young serum showed enhanced muscle regeneration and functional recovery, however, when extracellular vesicles (EV) are removed from these serums, this restorative effect disappears, indicating that these extracellular vesicles mediate the beneficial effects of young blood.
Further research found that these extracellular vesicles (EVs) carry mRNA encoding the anti-aging protein Klotho and deliver it to muscle progenitor cells, which are a kind of stem cells that are important for skeletal muscle regeneration. The extracellular vesicles (EV) collected from the blood of old mice carry less Klotho mRNA than those in young mice, so the muscle progenitor cells of old mice produce less Klotho protein.
Previously, Fabrisia Ambrosio's team had demonstrated that Klotho protein is an important regulator of muscle progenitor cell regeneration and that Klotho decreases with age. Therefore, as the age grows, muscle function begins to decline, and the ability to repair after injury also declines.
And this new study shows for the first time that the substances carried in extracellular vesicles (EVs) change with age, resulting in less important information transmitted to stem cells. This indicates that extracellular vesicles (EV) have the potential to be developed as a new therapy for the treatment of damaged muscle tissue.
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