Grant: Operating Grant

Many of the common diseases in humans arise primarily in the elderly or in individuals who are at risk due to a physiological compromise such as obesity, elevated blood pressure, etc. Our thesis is that some of the important diseases arise as a consequence of reduced ability of the patients to physiologically adapt to chronic stresses. We believe that SirT1 is a key component of the adaptation machinery and that by elevating the abundance of SirT1 we will be able to delay the onset and perhaps reverse the development of some of the diseases caused by such chronic stresses as obesity. Our approach is to use genetically modified strains of mice that we have create to first establish the validity of our idea (that increased SirT1 is of therapeutic benefit) and then to identify pharmacological agents that can increase SirT1 in normal mice and can thus affect therapeutic benefit more universally.