Skeletal muscle fibers (cells) show stripes, separated-100 times. Display: 6 skeletal muscle fibers (cells), stripes and multinucleated cells. [Ed Reschke/Getty Images]
A new study in a mouse model revealed a transcript that encodes a life-determining protein that travels through the systemic circulation in tiny shuttles called extracellular vesicles (EV), a key mediator of muscle tissue rejuvenation.
As we all know, muscles become weaker with age. They are significantly smaller, and their resistance to injury is also weaker. Aging muscle cannot heal well after injury, because it is not the restoration of the original muscle tissue, but the deposition of scar tissue.
As we all know, through a protocol called "alternative symbiosis", injecting blood from young animals into older animals can restore the youthful characteristics of aging muscles. Simultaneous symbiosis connects the circulatory systems of two animals, allowing older animals to come into contact with circulatory factors from young animals, and vice versa. What has not been known until now is the identity of the circulatory factor that regulates this rejuvenation in the blood of young people.
Scientists at the University of Pittsburgh have now determined that the transcript of the longevity protein (Klotho) in circulating EV contributes to the systemic regulation of aging skeletal muscle regeneration.
The authors show that when EVs in the blood are depleted, the beneficial effects of young blood on aging muscle regeneration are reduced. This indicates that the aging of muscle tissue is accompanied by loss of muscle function and impaired repair, which may be driven by aging EVs, which carry fewer copies of these instructions to promote longevity than EVs in young animals.
These new findings were published in an article in the journal Nature Aging entitled "Regulation of aging skeletal muscle regeneration through circulating extracellular vesicles", which provides new insights into the decline in muscle regeneration capacity with age.
Compared with circulating EVs in older animals (right), extracellular vesicles (EV) in the blood of young animals have more Klotho transcripts (left), represented by the green chain. The age-related decline in circulating EV-derived Klotho transcripts leads to delayed regeneration of skeletal muscle in injured elderly animals, which can be at least partially reversed by treating injured elderly skeletal muscles with young EVs. Use the graphics created by BioRender.com. [Fabrisia Ambrosio & Amrita Sahu] "We are very excited about this research for several reasons," said Dr. Fabrisia Ambrosio, director of rehabilitation at UPMC International, associate professor of physical medicine and rehabilitation at Pitt University, and senior author of the study. Paper. "It helps us understand the basic biology of how muscle regeneration works and how it fails with age. Taking this information to the next step, we can consider using extracellular vesicles as a treatment to counteract these age-related defect."
"We want to know whether extracellular vesicles might help muscle regeneration because these messengers travel from cell to cell through blood and other body fluids. Just like information in a bottle, electric cars deliver information to target cells," Pitt University Said Dr. Amrita Sahu, postdoctoral fellow in the Department of Physical Medicine and Rehabilitation and the first author of the paper.
Dr. Amrita Sahu, a postdoctoral fellow in the Department of Physical Medicine and Rehabilitation at the University of Pittsburgh, is the lead author of the paper [UPMC]. The research team isolated and characterized EVs from the serum of young and old mice—the blood remaining after removing blood cells and clotting factors. They observed that after injecting EVs from young mice into older mice with muscle injuries, mice that received young serum showed enhanced muscle regeneration and functional recovery compared with mice that received placebo. But when EVs are taken out, the restorative properties of young serum are lost, which indicates that EVs play a key role in transmitting the rejuvenating effect from young mice to old mice.
Dr. Fabrisia Ambrosio, Director of UPMC International Rehabilitation Center, Associate Professor of Physical Medicine and Rehabilitation at the University of Pittsburgh, is the senior author of the paper [Source: UPMC] "In this work, we use imaging flow cytometry to compare structures and individual nanoparticles The composition characteristics of young and aging EVs at high resolution. This method allows us to assess the dynamics of circulating EV subpopulations with age. We use machine learning methods for imaging flow cytometry data to compare young and old EVs. Classification," Ambrosio said. "Ultimately, we expect this information to provide important clues about which EV subgroups contribute the most to skeletal muscle healing, and how these subgroups change over time."
The authors found that using machine learning classifiers, aging changes the nucleic acid fingerprints of circulating EVs, but not the protein fingerprints. The authors showed that EV provides anti-aging Klotho mRNA to muscle progenitor cells. They also showed that EVs collected from older mice carried fewer copies of Klotho mRNA compared to younger mice, resulting in less Koltho protein in muscle progenitor cells.
Early work in the Ambrosio laboratory has determined that Klotho is an important regulator of muscle progenitor cell regeneration, and this protein will decline with age. New research shows that age-related changes in EV cargo can help reduce Klotho in aging muscle stem cells.
"Electric vehicles may help improve muscle regeneration in the elderly and improve functional recovery after injury," Ambrosio said.
The research reported in the current paper was supported by the National Institutes of Health and University of Pittsburgh Medical Center (UPMC) Enterprises.
"As the next step," Ambrosio said, "We are mainly focused on developing new technologies based on EVs to enhance muscle healing in the elderly. Specifically, we are studying ways to design EVs with molecular cargo (including Klotho transcripts), The goal is to optimize the downstream benefits of EVs on target muscle function. We are also investigating non-invasive methods, such as exercise, to increase Klotho transcription levels in elderly EVs."
In future research, Ambosio and co-author Radosveta Koldamova, MD, PhD, Professor of Environmental and Occupational Health at the Pitt Graduate School of Public Health, will also explore the role of electric vehicles in reversing age-related cognitive decline.
Comment after login