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Fibroblasts derived from long‐lived insulin receptor substrate 1 null mice are not resistant to multiple forms of stress
Authors:Melissa M Page  Amy Sinclair  Ellen L Robb  Jeffrey A Stuart  Dominic J Withers  Colin Selman
Institution:1. Integrative and Environmental Physiology, Institute of Biology and Environmental Sciences, University of Aberdeen, , Aberdeen, AB24 2TZ UK;2. Institute of Biodiversity, Animal Health and Comparative Medicine, College of Medicine, Veterinary and Life Sciences, Graham Kerr Building, University of Glasgow, , Glasgow, G12 8QQ UK;3. Department of Biological Sciences and Cold Climate Oenology and Viticulture Institute, Brock University, , St. Catharines, ON, L2S 3A1 Canada;4. Metabolic Signaling Group, Medical Research Council Clinical Sciences Centre, Imperial College, , London, W12 0NN UK
Abstract:Reduced signalling through the insulin/insulin-like growth factor-1 signalling (IIS) pathway is a highly conserved lifespan determinant in model organisms. The precise mechanism underlying the effects of the IIS on lifespan and health is currently unclear, although cellular stress resistance may be important. We have previously demonstrated that mice globally lacking insulin receptor substrate 1 (Irs1?/?) are long-lived and enjoy a greater period of their life free from age-related pathology compared with wild-type (WT) controls. In this study, we show that primary dermal fibroblasts and primary myoblasts derived from Irs1?/? mice are no more resistant to a range of oxidant and nonoxidant chemical stressors than cells derived from WT mice.
Keywords:aging  IRS1  NRF2  oxidative stress  stress resistance
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