SIRT1 transgenic mice show phenotypes resembling calorie restriction |
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Authors: | Bordone Laura Cohen Dena Robinson Ashley Motta Maria Carla van Veen Ed Czopik Agnieszka Steele Andrew D Crowe Hayley Marmor Stephen Luo Jianyuan Gu Wei Guarente Leonard |
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Affiliation: | Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; The Whitehead Institute, Cambridge, MA 02142, USA; Diabetes and Metabolism Disease Area, Novartis Institutes for BioMedical Research, Inc., Cambridge, MA 02139, USA; Institute of Cancer Genetics and Department of Pathology, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA |
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Abstract: | We generated mice that overexpress the sirtuin, SIRT1. Transgenic mice have been generated by knocking in SIRT1 cDNA into the β-actin locus. Mice that are hemizygous for this transgene express normal levels of β-actin and higher levels of SIRT1 protein in several tissues. Transgenic mice display some phenotypes similar to mice on a calorie-restricted diet: they are leaner than littermate controls; are more metabolically active; display reductions in blood cholesterol, adipokines, insulin and fasted glucose; and are more glucose tolerant. Furthermore, transgenic mice perform better on a rotarod challenge and also show a delay in reproduction. Our findings suggest that increased expression of SIRT1 in mice elicits beneficial phenotypes that may be relevant to human health and longevity. |
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Keywords: | calorie restriction SIRT1 transgenic mice |
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