Neuronal SIRT1 regulates endocrine and behavioral responses to calorie restriction.
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.
Cohen
Dena E
DE
Paul F. Glenn Laboratory, Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
Supinski
Andrea M
AM
Bonkowski
Michael S
MS
Donmez
Gizem
G
Guarente
Leonard P
LP
D000818:Animals; D001522:Behavior, Animal / Q000502:physiology*; D031204:Caloric Restriction; D004032:Diet; D004703:Endocrine System / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism; D018149:Glucose Intolerance / Q000378:metabolism; D008136:Longevity / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009474:Neurons / Q000378:metabolism; D015398:Signal Transduction; D056564:Sirtuin 1 / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism*
C470545:Sirt1 protein, mouse; D056564:Sirtuin 1; D005947:Glucose