title: Effect of caloric restriction on the SIRT1/mTOR signaling pathways in senile mice.
abstract: OBJECTIVE
  To determine the effects and underlying molecular mechanisms of caloric restriction (CR) in C57BL/6 mice.
  
  
  METHODS
  Thirty-six 6-week-old male C57BL/6 mice were assigned to a normal control group (NC, n=12), a high energy group (HE, n=12), and a CR group (n=12), and received a normal diet, a high-calorie diet, or a calorie-restricted diet, respectively, for 44 weeks. Body weight and serum glucose concentration were regularly recorded, and animals were sacrificed and hippocampus tissues were collected for immunohistochemistry (n=6 per group), western blotting (n=3 per group) and real-time polymerase chain reaction (n=3 per group) analysis at the end of the 44-week experimental period. Immunohistochemistry, western blotting and real-time polymerase chain reaction were used to detect changes in hippocampal proteins may be involved in the SIRT1/mTOR pathways.
  
  
  RESULTS
  Body weight and serum glucose over the 44 weeks in animals from the CR group were lower than those of HE group. The number of SIRT1-immunoreactive cells in the CR group was significantly higher than in the NC and HE groups, and SIRT1 mRNA expression in the CR group was significantly higher than that in the HE group, but there was no difference in SIRT1 protein expression among the three groups. mTOR and S6K1 protein activation and mTOR and S6K1 mRNA were significantly lower in the CR group than in the NC group.
  
  
  CONCLUSIONS
  Our findings suggest that a CR diet could lead to activation of SIRT1 and suppression of mTOR and S6K1 activation in C57BL/6 mice. We have shown that the SIRT1/mTOR signaling pathways may be involved in the neuroprotective effect of CR.
authors.affiliation: Department of Geriatrics, Xuan Wu Hospital, Capital Medical University, Beijing 100053, China; Central Laboratory, Xuan Wu Hospital, Capital Medical University, Key Laboratory for Neurodegenerative Disease of Ministry of Education, Center of Alzheimer's Disease, Beijing Institute for Brain Disorders, Beijing 100053, China.
authors.forename: Lina
authors.initials: L
authors.lastname: Ma
authors.affiliation: Central Laboratory, Xuan Wu Hospital, Capital Medical University, Key Laboratory for Neurodegenerative Disease of Ministry of Education, Center of Alzheimer's Disease, Beijing Institute for Brain Disorders, Beijing 100053, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Dong
authors.affiliation: Central Laboratory, Xuan Wu Hospital, Capital Medical University, Key Laboratory for Neurodegenerative Disease of Ministry of Education, Center of Alzheimer's Disease, Beijing Institute for Brain Disorders, Beijing 100053, China. Electronic address: rong_wang72@aliyun.com.
authors.forename: Rong
authors.initials: R
authors.lastname: Wang
authors.affiliation: Department of Geriatrics, Xuan Wu Hospital, Capital Medical University, Beijing 100053, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Neurology, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, China.
authors.forename: Baolei
authors.initials: B
authors.lastname: Xu
authors.affiliation: Central Laboratory, Xuan Wu Hospital, Capital Medical University, Key Laboratory for Neurodegenerative Disease of Ministry of Education, Center of Alzheimer's Disease, Beijing Institute for Brain Disorders, Beijing 100053, China.
authors.forename: Jingshuang
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Central Laboratory, Xuan Wu Hospital, Capital Medical University, Key Laboratory for Neurodegenerative Disease of Ministry of Education, Center of Alzheimer's Disease, Beijing Institute for Brain Disorders, Beijing 100053, China.
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Zhao
authors.affiliation: Central Laboratory, Xuan Wu Hospital, Capital Medical University, Key Laboratory for Neurodegenerative Disease of Ministry of Education, Center of Alzheimer's Disease, Beijing Institute for Brain Disorders, Beijing 100053, China.
authors.forename: Yulan
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000818:Animals; D001786:Blood Glucose; D015153:Blotting, Western; D001835:Body Weight; D031204:Caloric Restriction; D003704:Dementia / Q000178:diet therapy* / Q000378:metabolism* / Q000473:pathology; D005455:Fluorescent Antibody Technique; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D038744:Ribosomal Protein S6 Kinases, 90-kDa / Q000378:metabolism; D015398:Signal Transduction; D056564:Sirtuin 1 / Q000378:metabolism*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*
chemical_list: D001786:Blood Glucose; D012333:RNA, Messenger; C546843:mTOR protein, mouse; D038744:Ribosomal Protein S6 Kinases, 90-kDa; C512964:Rps6ka1 protein, mouse; D058570:TOR Serine-Threonine Kinases; C470545:Sirt1 protein, mouse; D056564:Sirtuin 1
keywords: Caloric restriction; S6K1; SIRT1; mTOR