SIRT1 on the brain: Sirtuin controls behavior under CR

Not only does the mammalian sirtuin SIRT1 mediate the lifespan extension phenotype of caloric restriction (CR), it is also involved in controlling behavior (such as food intake) in response to CR (and possibly during ad libitum feeding as well).

Two recent papers with consistent results address the issue. Both studies employed brain-specific knockouts of SIRT1; Cohen et al. used a brain-specific knockout, whereas Çakir et al. used both pharmacologic inhibition and an siRNA in the hypothalamus. The latter paper implicates the FoxO1 transcription factor and S6 kinase signaling, implying cross-talk with both the IGF-1 and TOR pathways.

ResearchBlogging.orgÇakir, I., Perello, M., Lansari, O., Messier, N., Vaslet, C., & Nillni, E. (2009). Hypothalamic Sirt1 Regulates Food Intake in a Rodent Model System PLoS ONE, 4 (12) DOI: 10.1371/journal.pone.0008322

Cohen, D., Supinski, A., Bonkowski, M., Donmez, G., & Guarente, L. (2009). Neuronal SIRT1 regulates endocrine and behavioral responses to calorie restriction Genes & Development, 23 (24), 2812-2817 DOI: 10.1101/gad.1839209