Research Paper Advance Articles

Figure 5. Senescence stimuli specific exosome lipid signatures in primary human lung fibroblasts (IMR90). (A) Summary of significantly altered exosome lipids (p-value < 0.05 and > 2-fold change) from senescent human lung fibroblasts compared to quiescent cells following IR, doxo, and MiDAS senescence induction. (B) Partial least squares-discriminant analysis (PLS-DA) clustered senescent human lung fibroblasts from Quiescent (control) based on 247 lipids (i) Low serum media (LSM; Qui IR-mock control) vs IR (ii) Low serum media (Qui DMSO control) vs doxo and MiDAS. (C) Heatmap of 145 differentially expressed exosome lipids from 15 different classes. Clustering was performed using Euclidean distance and complete linkage and log₂ fold change is illustrated to visualize trends with the three senescence inducers. (D) Violin plots showing three examples of individual lipid profiles where PC(18:0/20:4) and SM(d18:2/16:0) were upregulated with all senescence inducers, while TG(54:6) was downregulated in IR and doxo but not MiDAS, illustrating lipid response differences due to different stimuli. AC: Acylcarnitine, Cer: Ceramide, FA: Fatty acid, HexCer: Hexosylceramide, LPC: Lysophosphatidylcholine, PA: Phosphatidic acid, PC: Phosphatidylcholine, PE: Phosphatidylethanolamine, PG: Phosphatidylglycerol, PI: Phosphatidylinositol, PS: Phosphatidylserine, SM: Sphingomyelin, TG: Triglycerides.