SIRT1 transgenic mice show phenotypes resembling calorie restriction.
We generated mice that overexpress the sirtuin, SIRT1. Transgenic mice have been generated by knocking in SIRT1 cDNA into the beta-actin locus. Mice that are hemizygous for this transgene express normal levels of beta-actin and higher levels of SIRT1 protein in several tissues. Transgenic mice display some phenotypes similar to mice on a calorie-restricted diet: they are leaner than littermate controls; are more metabolically active; display reductions in blood cholesterol, adipokines, insulin and fasted glucose; and are more glucose tolerant. Furthermore, transgenic mice perform better on a rotarod challenge and also show a delay in reproduction. Our findings suggest that increased expression of SIRT1 in mice elicits beneficial phenotypes that may be relevant to human health and longevity.
Bordone
Laura
L
Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Cohen
Dena
D
Robinson
Ashley
A
Motta
Maria Carla
MC
van Veen
Ed
E
Czopik
Agnieszka
A
Steele
Andrew D
AD
Crowe
Hayley
H
Marmor
Stephen
S
Luo
Jianyuan
J
Gu
Wei
W
Guarente
Leonard
L
D054392:Adipokines / Q000097:blood; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D031204:Caloric Restriction; D002784:Cholesterol / Q000097:blood; D007328:Insulin / Q000097:blood; D008136:Longevity / Q000235:genetics*; D051379:Mice; D008822:Mice, Transgenic; D010641:Phenotype; D056564:Sirtuin 1; D037761:Sirtuins / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
D054392:Adipokines; D001786:Blood Glucose; D007328:Insulin; D002784:Cholesterol; C470545:Sirt1 protein, mouse; D056564:Sirtuin 1; D037761:Sirtuins