As muscles get older, their cells become less capable of regenerating and healing after injuries. Recently, Cornell University researchers have mapped out how this decline occurs over time in mice, providing the most thorough analysis to date.
As muscles get older, their cells become less capable of regenerating and healing after injuries. Recently, Cornell University researchers have mapped out how this decline occurs over time in mice, providing the most thorough analysis to date.
Ben Cosgrove, an associate professor of biomedical engineering and the lead author of the paper, explained, “The main question that guided our research was one that had puzzled the skeletal muscle biology community. Is the decreased ability for old muscles to regenerate due to changes in the stem cells responsible for repair, or is it because of modifications in how other cell types instruct these stem cells?”
The research, published in Nature Aging, involved collecting cells from young, old, and geriatric mice at six different intervals after prompting an injury with a specific type of snake venom toxin. The team identified 29 distinct cell types, noting that immune cells varied in their quantity and response times across different age groups, along with muscle stem cells that thrive in youth but struggle as muscles age.
The extensive evaluation of various cell types over time revealed a lack of coordination in the muscle repair processes of older mice. Many immune cells responsible for coordinating tissue recovery arrived at inappropriate times.
“There are either too many or too few immune cells present,” Cosgrove commented. “These immune cells are ‘playing the wrong music.’ They’re not in sync with each other in the older muscles.”
The research team utilized a new approach to assess cellular senescence, the point at which a cell can no longer divide.
“We developed what we are terming a transfer-learning based method,” stated Lauren Walter, the lead author and a doctoral student in Cosgrove’s laboratory during the study. “We leveraged an existing set of genes to determine a cell’s senescence status, then applied this methodology to evaluate senescence relative to age and regeneration time points.”
This study enhances the understanding of how different cell types interact and induce senescence, which may help guide the development of therapies targeting senescent cells.
This research was funded by the U.S. National Institutes of Health, the Bloomberg~Kimmel Institute, and the Morton Goldberg Professorship.
