Insulin-like growth factor binding protein-6 delays replicative senescence of human fibroblasts
نویسندگان
چکیده
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.
منابع مشابه
IGF Binding Protein-5 Induces Cell Senescence
Cellular senescence is the complex process of deterioration that drives the aging of an organism, resulting in the progressive loss of organ function and eventually phenotypic aging. Senescent cells undergo irreversible growth arrest, usually by inducing telomere shortening. Alternatively, senescence may also occur prematurely in response to various stress stimuli, such as oxidative stress, DNA...
متن کاملInduction of cellular senescence by insulin-like growth factor binding protein-5 through a p53-dependent mechanism.
The insulin-like growth factor (IGF) signaling pathway plays a crucial role in the regulation of cell growth, differentiation, apoptosis, and aging. IGF-binding proteins (IGFBPs) are important members of the IGF axis. IGFBP-5 is up-regulated during cellular senescence in human dermal fibroblasts and endothelial cells, but the function of IGFBP-5 in cellular senescence is unknown. Here we show t...
متن کاملThe Effect of 8 Weeks Resistance Training With Low Load and High Load on Testosterone, Insulin-like Growth Factor-1, Insulin-like Growth Factor Binding Protein-3 Levels, and Functional Adaptations in Older Women
Objectives The loss of muscle mass in older adults is attributed to the impaired ability of the skeletal muscle in response to anabolic stimuli and the increased activation of the proteolytic signaling pathway. With increasing age, plasma concentrations of circulating anabolic hormones and growth factors, e.g. testosterone, Insulin-like Growth Factor-1 (IGF-1) and Insulin-like Growth Factor Bin...
متن کاملBrain-derived neurotrophic factor, insulin-like growth factor-I and its binding protein responses to a session of endurance exercise in healthy elderly men
Purpose: This study investigated the effect of endurance activity on brain-derived neurotrophic factor(BDNF), insulin-like growth factor 1(IGF-1) and its binding protein 3(IGFBP-3) in elderly healthy individuals. Materials and Methods: Eleven healthy old males (mean age of 68 ± 2.31 years old, height of 177 ± 3.1 cm and weight of 79 ± 1.5 kg) were studied. Seventy two hours after maxi...
متن کاملPlasminogen activator inhibitor 1--insulin-like growth factor binding protein 3 cascade regulates stress-induced senescence.
Cellular senescence is widely believed to play a key role in tumor suppression, but the molecular pathways that regulate senescence are only incompletely understood. By using a secretome proteomics approach, we identified insulin-like growth factor binding protein 3 (IGFBP3) as a secreted mediator of breast cancer senescence upon chemotherapeutic drug treatment. The senescence-inducing activity...
متن کامل