Insulin-like growth factor binding protein-6 delays replicative senescence of human fibroblasts

Publication date: October 2011 Source:Mechanisms of Ageing and Development, Volume 132, Issue 10 Author(s): Lucia Micutkova , Thomas Diener , Chen Li , Adelina Rogowska-Wrzesinska , Christoph Mueck , Eveline Huetter , Birgit Weinberger , Beatrix Grubeck-Loebenstein , Peter Roepstorff , Rong Zeng , Pidder Jansen-Duerr 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. Highlights ► Proteomic analysis of senescent secretome reveals upregulation of IGFBP-6 in fibroblasts. ► IGFBP-6 knockdown induces premature senescence in young fibroblasts. ► IGFBP-6 lentiviral overexpression delays repl...

Source: Mechanisms of Ageing and Development - November 7, 2014 Category: Geriatrics Source Type: research