title: Insulin-like growth factor binding protein-6 delays replicative senescence of human fibroblasts.
abstract: Cellular senescence can be induced by a variety of mechanisms, and recent data suggest a key role for cytokine networks to maintain the senescent state. Here, we have used a proteomic LC-MS/MS approach to identify new extracellular regulators of senescence in human fibroblasts. We identified 26 extracellular proteins with significantly different abundance in conditioned media from young and senescent fibroblasts. Among these was insulin-like growth factor binding protein-6 (IGFBP-6), which was chosen for further analysis. When IGFBP-6 gene expression was downregulated, cell proliferation was inhibited and apoptotic cell death was increased. Furthermore, downregulation of IGFBP-6 led to premature entry into cellular senescence. Since IGFBP-6 overexpression increased cellular lifespan, the data suggest that IGFBP-6, in contrast to other IGF binding proteins, is a negative regulator of cellular senescence in human fibroblasts.
authors.affiliation: Institute for Biomedical Aging Research, Austrian Academy of Sciences, Rennweg 10, A-6020 Innsbruck, Austria.
authors.forename: Lucia
authors.initials: L
authors.lastname: Micutkova
authors.forename: Thomas
authors.initials: T
authors.lastname: Diener
authors.forename: Chen
authors.initials: C
authors.lastname: Li
authors.forename: Adelina
authors.initials: A
authors.lastname: Rogowska-Wrzesinska
authors.forename: Christoph
authors.initials: C
authors.lastname: Mueck
authors.forename: Eveline
authors.initials: E
authors.lastname: Huetter
authors.forename: Birgit
authors.initials: B
authors.lastname: Weinberger
authors.forename: Beatrix
authors.initials: B
authors.lastname: Grubeck-Loebenstein
authors.forename: Peter
authors.initials: P
authors.lastname: Roepstorff
authors.forename: Rong
authors.initials: R
authors.lastname: Zeng
authors.forename: Pidder
authors.initials: P
authors.lastname: Jansen-Duerr
mesh_terms: D000328:Adult; D000368:Aged; D000375:Aging / Q000097:blood; D000595:Amino Acid Sequence; D017209:Apoptosis / Q000235:genetics / Q000502:physiology; D001483:Base Sequence; D049109:Cell Proliferation; D002470:Cell Survival / Q000235:genetics / Q000502:physiology; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000235:genetics / Q000502:physiology*; D017931:DNA Primers / Q000235:genetics; D015536:Down-Regulation; D005347:Fibroblasts / Q000166:cytology / Q000502:physiology; D055785:Gene Knockdown Techniques; D006801:Humans; D018976:Insulin-Like Growth Factor Binding Protein 6 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D008969:Molecular Sequence Data; D034741:RNA, Small Interfering / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D015854:Up-Regulation
chemical_list: D017931:DNA Primers; D018976:Insulin-Like Growth Factor Binding Protein 6; D034741:RNA, Small Interfering