biostudies-literatureJelleschitz SAustrian Science Fund FWFÖsterreichische Nationalstiftung für Forschung, Technologie und EntwicklungChristian Doppler Forschungsgesellschaft104069https://www.ebi.ac.uk/biostudies/studies/S-EPMC12925199biostudies-literatureUnknown91Senescent dermal fibroblasts accumulate and secrete chemically reactive lipids that are components of the senescence-associated secretory phenotype (SASP). These lipids, including 4-hydroxynonenal (HNE) and reactive oxidized phospholipids (OxPL), covalently bind to and modify proteins via Schiff base formation or Michael adduction. Our study examined lipid-induced collagen modifications and their impact on skin cells to evaluate the long-term consequences of senescent cells on the tissue microenvironment. Using mass spectrometry and biochemical analyses, we identified both high and low molecular-weight modifications to collagen types I, II and IV. Collagen modified by HNE reduced fibroblast proliferation and induced stress responses. In contrast, collagen modified by OxPL provoked inflammaRedox biologyModification of the dermal matrix by senescence associated lipids and its functional consequence.PMC12925199I-5627Mildner MNarzt MSNagelreiter IMFedorova MJelleschitz SBauer CTessier ASchirato MSandgren Fors ANi ZGendronneau GKremslehner CBen Khalifa YStiegler AFreystatter CMarcato FAndre NOskolkova OSalek MGruber FfalseModification of the dermal matrix by senescence associated lipids and its functional consequence.Senescent dermal fibroblasts accumulate and secrete chemically reactive lipids that are components of the senescence-associated secretory phenotype (SASP). These lipids, including 4-hydroxynonenal (HNE) and reactive oxidized phospholipids (OxPL), covalently bind to and modify proteins via Schiff base formation or Michael adduction. Our study examined lipid-induced collagen modifications and their impact on skin cells to evaluate the long-term consequences of senescent cells on the tissue microenvironment. Using mass spectrometry and biochemical analyses, we identified both high and low molecular-weight modifications to collagen types I, II and IV. Collagen modified by HNE reduced fibroblast proliferation and induced stress responses. In contrast, collagen modified by OxPL provoked inflamma2026-01-01T00:00:00Z2026 Feb2026-07-10T03:22:46.237Z2026-07-10T03:10:20.593ZS-EPMC129251994169011710.1016/j.redox.2026.104069