Sunday, December 08, 2024

Mouse study captures and maps aging process of skeletal muscles at the cellular level and in great detail

Good news! It is always good to have a detailed atlas! 

These poor mice were subjected to snake venom.

"As muscles age, their cells lose the ability to regenerate and heal after injury. Cornell Engineering researchers have created the most comprehensive portrait to date of how that change, in mice, unfolds over time and across the complicated architecture of muscle tissue. ...

“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?” ...

researchers sampled cells from young, old and geriatric mice at six time points after inducing injury via a variant of snake venom toxin. They identified 29 defined cell types, including immune cells that exhibited differences in their abundance and reaction time between age groups, and muscle stem cells that self-renew in youth but stall out as muscles age. ...

The detailed assessment of many cell types over time showed discoordination in the process of muscle repair in older mice. Many immune cells, which coordinate tissue repair, show up at the wrong time. ..."

From the abstract:
"In aging, skeletal muscle regeneration declines due to alterations in both myogenic and non-myogenic cells and their interactions. This regenerative dysfunction is not understood comprehensively or with high spatiotemporal resolution. We collected an integrated atlas of 273,923 single-cell transcriptomes and high-resolution spatial transcriptomic maps from muscles of young, old and geriatric mice (~5, 20 and 26 months old) at multiple time points following myotoxin injury. We identified eight immune cell types that displayed accelerated or delayed dynamics by age. We observed muscle stem cell states and trajectories specific to old and geriatric muscles and evaluated their association with senescence by scoring experimentally derived and curated gene signatures in both single-cell and spatial transcriptomic data. This revealed an elevation of senescent-like muscle stem cell subsets within injury zones uniquely in aged muscles. This Resource provides a holistic portrait of the altered cellular states underlying muscle regenerative decline across mouse lifespan."

Mouse study captures aging process at the cellular level | Cornell Chronicle



Fig. 1: Assembly of scRNA-seq atlas of skeletal muscle regeneration across mouse aging.



Fig. 2: Age-related changes to cell dynamics during skeletal muscle regeneration.


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