Sirt1 gene is required for the increase in physical activity induced by caloric restrictions

Caloric restriction (CR) is the best known approach to extend organism’s lifespan. It works remarkably well in various living beings, from yeast to mice. It is likely also to work in primates and humans. If an animal lives under CR, essentially semi-starving, one may think that it will try to preserve its energy by reducing physical activity. Apparently, this is not the case. For example, mice in reality move more and demonstrate increased foraging activity while on a restricted diet. This does make sense as far as individual’s survival is concerned. In the wild, mice confronted with food shortage are more likely to find more food when they try to search for it than if they simply sit there hoping for a piece of cheese to appear out of thin air.

I have recently written about Sir2, a gene critical for longevity in different organisms. Sir2 is multi-facet gene and may have opposite roles as far as longevity is concerned in different cell types. In the paper published this week in Science the authors add another evidence for Sir2 role in CR induced longevity in mammals. Sir2 homologue from mice, Sirt1, turns out to be needed for the increased activity induced by calorie restrictions in mice. The mice lacking Sirt1 demonstrate various biochemical changes triggered by CR (for example, reduction of blood glucose) just like the wild-type mice. But, starved Sirt1 animals are no more active than the animals fed to their full. Thus, Sirt1 is important for starvation induced physical activity. It will be very interesting to see if Sirt1 is also required for life-span extension. Apparently, because Sirt1 gene deletion has only been engineered recently, the mice missing Sirt1 gene are still too young to tell if Sirt1 is required for their longevity under calorie restriction.

Ok, calorie restricted mice demonstrate enhanced physical activity. But what about their sex lives? Are they as sexually active as their relatives who enjoy fuller plates? Could CR mice be in fact more sexually active just as they are more physically active? My guess is that most likely CR mice are less sexually active than their well-fed brothers and sisters. The reason for this is that while the mouse may not able to compromise its foraging activity when threatened with looming starvation, it can more easily forgo sexual activities to preserve the limited energy that is critically needed to hunt for food.


Reference
Science 9 December 2005:
Vol. 310. no. 5754, p. 1641
DOI: 10.1126/science.1118357

Increase in Activity During Calorie Restriction Requires Sirt1
Danica Chen, Andrew D. Steele, Susan Lindquist, Leonard Guarente

Sir2 (silent information regulator 2) is a nicotinamide adenine dinucletide-dependent deacetylase required for longevity due to calorie restriction in yeast and Drosophila. In mammals, calorie restriction induces a complex pattern of physiological and behavioral changes. Here we report that the mammalian Sir2 ortholog, Sirt1, is required for the induction of a phenotype by calorie restriction in mice.