title: Regulation of lipids is central to replicative senescence.
abstract: Cellular replicative senescence, a state of permanent cell-cycle arrest, has been linked to organismal aging, tissue repair and tumorigenesis. In this study, we comparatively investigated the global lipid profiles and mRNA content of proliferating and senescent-state BJ fibroblasts. We found that both expression levels of lipid-regulating genes and the abundance of specific lipid families, are actively regulated. We further found that 19 specific polyunsaturated triacylglycerol species constituted the most prominent changes in lipid composition during replicative senescence. Based on the transcriptome analysis, we propose that the activation of CD36-mediated fatty acid uptake and diversion to glycerolipid biosynthesis could be responsible for the accumulation of triacylglycerols during replicative senescence. This, in turn, could be a cellular mechanism to prevent lipotoxicity under increased oxidative stress conditions observed in this process. Our results indicate that regulation of specific lipid species has a central role during replicative senescence.
authors.affiliation: Department of Chemistry, University at Buffalo, The State University of New York (SUNY), Buffalo, NY 14260 USA. ekinatil@buffalo.edu.
authors.forename: Darleny Y
authors.initials: DY
authors.lastname: Lizardo
authors.affiliation: Department of Biological Sciences, University at Buffalo, The State University of New York (SUNY), Buffalo, NY 14260 USA. gokcumen@gmail.com.
authors.forename: Yen-Lung
authors.initials: YL
authors.lastname: Lin
authors.affiliation: Department of Biological Sciences, University at Buffalo, The State University of New York (SUNY), Buffalo, NY 14260 USA. gokcumen@gmail.com.
authors.forename: Omer
authors.initials: O
authors.lastname: Gokcumen
authors.affiliation: Department of Chemistry, University at Buffalo, The State University of New York (SUNY), Buffalo, NY 14260 USA. ekinatil@buffalo.edu.
authors.forename: G Ekin
authors.identifier: http://orcid.org/0000-0002-7132-3873
authors.initials: GE
authors.lastname: Atilla-Gokcumen
mesh_terms: D002460:Cell Line; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000502:physiology*; D016000:Cluster Analysis; D005347:Fibroblasts / Q000378:metabolism; D020869:Gene Expression Profiling; D050356:Lipid Metabolism; D053858:Metabolic Networks and Pathways; D055432:Metabolomics / Q000379:methods; D059467:Transcriptome