Comprehensive Analysis of Cellular and Molecular Changes

The ability of muscle cells to regenerate and recover from injuries diminishes with age. In the most thorough depiction to date, researchers from Cornell Engineering have shown how that change occurs in mice over time and throughout the intricate structure of muscle tissue.

The fundamental question that drove the initial study was really a question that had perplexed the skeletal muscle biology community. Does the decline in regeneration seen in old muscles come from changes to the stem cells that drive the repair process themselves, or does it come from changes in the way that they are instructed by other cell types?”

Ben Cosgrove, Associate Professor and Study Senior Author, Meinig School of Biomedical Engineering, Cornell University

Researchers took samples of cells from young, elderly, and geriatric mice at six different intervals after causing harm with a particular type of snake venom toxin for their study, published in the journal Nature Aging.

They discovered 29 distinct cell types, such as muscle stem cells that self-renew in youth but stop doing so as muscles age and immune cells that varied in quantity and response time between age groups.

Over time, the thorough evaluation of numerous cell types revealed inconsistencies in the older mice's muscle repair process. The timing of the appearance of many immune cells, which coordinate tissue repair, is off.

There is too many of them or too few of them. The immune cells are playing the wrong music. They are out of step with each other in the older muscles.”

Ben Cosgrove, Associate Professor and Study Senior Author, Meinig School of Biomedical Engineering, Cornell University

The research team used a novel technique to assess senescence, or the inability of a cell to divide.

We developed what we are calling a transfer-learning based method. We used an existing list of genes to score a cell’s senescence status and then used that methodology to evaluate senescence across age and regeneration time point.”

Lauren Walter, Study Lead Author and Doctoral Student, Cornell University

The study advances the knowledge of how different cell types interact to cause senescence, which may help develop medications that specifically target senescent cells.

Cosgrove said, “What our dataset provides is a rich template to really investigate what would be the benefits or detriments of removing senescent cells from tissues. The reason why people do this in mouse models is that we can really test out those hypotheses directly so that we can better understand the benefits of targeting senescent cells to improve the repair processes in older individuals.”