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Neuronal SIRT1 regulates endocrine and behavioral responses to calorie restriction

2009; Cold Spring Harbor Laboratory Press; Volume: 23; Issue: 24 Linguagem: Inglês

10.1101/gad.1839209

1549-5477

Dena E. Cohen, Andrea Supinski, Michael S. Bonkowski, Gizem Dönmez, Leonard Guarente,

Genetics, Aging, and Longevity in Model Organisms

Mammalian life span can be extended by both calorie restriction (CR) and mutations that diminish somatotropic signaling. Sirt1 is a mediator of many effects of CR in mammals, but any role in controlling somatotropic signaling has not been shown. Since the somatotropic axis is controlled by the brain, we created mice lacking Sirt1 specifically in the brain and examined the impacts of this manipulation on somatotropic signaling and the CR response. These mutant mice displayed defects in somatotropic signaling when fed ad libitum, and defects in the endocrine and behavioral responses to CR. We conclude that Sirt1 in the brain is a link between somatotropic signaling and CR in mammals.