Effect of caloric restriction on the expression of the Sirtuin Proteins

SirT1 is a deacetylase whose expression and activity increases during times of caloric restriction (CR). CR has been implicated lifespan extension in rodents, flies and worms, and SirT1 appears to be required for this increased longevity. Sirtuins have also been implicated in the regulation of transcriptional events, apoptosis, and energy efficiency. Many of the sirtuin proteins are similar in function, although they vary in cellular location. Interestingly, numerous studies demonstrated SirT1 activity during CR, but CR effects on the remaining six sirtuin proteins remains relatively unknown. This study aims to analyze the expression of sirtuins in a variety of tissues from mice subjected to a two week 60% CR. We hypothesize that CR will cause increases in mRNA levels of multiple sirtuins. Male and female mice were monitored daily to determine their individual food intake for two weeks and were then given 60% of their normal daily intake for two weeks. Animals were euthanized and tissues snap frozen and stored until further processing. We will present data showing the levels of SirT1–7 as well as other important metabolic and reproductive genes in response to CR. This work is supported by NIH grants U54 HD012303 and T32 DK007494.