Oral Presentation Australian Diabetes Society and the Australian Diabetes Educators Association Annual Scientific Meeting 2014

SIRT1 improves metabolic function in mice (#169)

Hassina Massudi 1 , David A Sinclair 1 2 , Lindsay E Wu 1
  1. Laboratory for Ageing Research, School of Medical Sciences, University of New South Wales, Sydney, NSW, Australia
  2. Glenn Labs for the Biological Mechanisms of Aging, Harvard Medical School, Boston, MA, United States

Sirt1, a member of class III nicotinamide adenine dinucleotide (NAD+)- dependent deacetylases, is involved in regulating adaptive pathways to cellular stress cues such as calorie restriction and is strongly linked to improving health and lifespan . Overexpression of Sirt1 is known to increase metabolic efficiency in numerous organisms including yeast worms, flies and rodents.  Here we show data from a SIRT1 transgenic mouse line that constitutively overexpress elevated levels (>x5) of SIRT1 compared to lower levels (1.5-2 fold) in previously described transgenic mice. While mitochondrial function has been previously reported to increase in response to the overexpression of SIRT1, in this study, we show that this may be mediated through an overall increase in complex IV of the respiratory chain mediated respiration. These transgenic mice also display phenotypes similar to calorie restriction, performing better on several metabolic parameters, including better glucose tolerance, lower insulin levels, and are more insulin sensitive. They also display a lower body weight and fat mass compared to wild type littermates. These findings have important implications in offering opportunities for therapeutic interventions in several diseases such as type II diabetes.