Integrative cross-species analysis reveals conserved and unique signatures in fatty skeletal muscles

Fat infiltration in skeletal muscle is now recognized as a standard feature of aging and is directly related to the decline in muscle function. However, there is still a limited systematic integration and exploration of the mechanisms underlying the occurrence of myosteatosis in aging across species. Here, we re-analyzed bulk RNA-seq datasets to investigate the association between fat infiltration in skeletal muscle and aging. Our integrated analysis of single-nucleus transcriptomics in aged humans and Laiwu pigs with high intramuscular fat content, identified species-preference subclusters and revealed core gene programs associated with myosteatosis. Furthermore, we found that fibro/adipogenic progenitors (FAPs) had potential capacity of differentiating into PDE4D⁺/PDE7B⁺ preadipocytes across species. Additionally, cell-cell communication analysis revealed that FAPs may be associated with other adipogenic potential clusters via the COL4A2 and COL6A3 pathways. Our study elucidates the correlation mechanism between aging and fat infiltration in skeletal muscle, and these consensus signatures in both humans and pigs may contribute to increasing reproducibility and reliability in future studies involving in the field of muscle research.