Fig. 2

Changes in transcriptional profiles of different cell types during relatively healthy aging, age-associated frailty, and age-independent frailty. (a) Flowchart overview of scRNA-seq methodology. (b) Summary of mice and number of cells with scRNA-seq results that passed quality control assessment. (c) Uniform manifold approximation and projection (UMAP) plots showing different cell types in the scRNA-seq samples. The dot plot on the right shows the marker genes for distinct cell types marked with different colors. The color scale indicates the average expression of marker genes in each cell type, and the dot size is proportional to the percentage of cells within each cell cluster expressing the marker genes. (d-f) Bi-directional bar plot showing the number of different genes in 13 cell types in the age-independent frailty (AIF, F-O vs. NF-O) (d), age-associated frailty (AAF, F-O vs. NF-Y) (e) and relatively healthy aging (RHA, NF-O vs. NF-Y) groups (f). Green indicates down-regulated genes, and red indicates up-regulated genes. (g) Heatmaps showing the distribution of DEGs in each cell type in different groups, including AAF, RHA, and AIF. Each row represents one cell type, and each column represents one gene. Red represents up-regulated DEGs, blue DEGs are down-regulated, and gray genes are unchanged. The gene sets were defined as follows: set 1 contained genes not significantly down-regulated in the AIF, RHA, and AAF groups. Set 2 comprised genes not significantly up-regulated in any group, and all remaining genes were assigned to set 3. The genes in set 3 were systematically sorted by cell type (alphabetical ascending) in each comparison group, then by p-value (ascending) and fold-change (descending), revealing three distinct expression patterns: pattern 1 was predominantly observed in AIF-DEGs, pattern 2 was most prominent in RHA-DEGs, and pattern 3 was characteristic of AAF-DEGs.