PMID- 24525424
OWN - NLM
STAT- MEDLINE
DCOM- 20141105
LR  - 20140318
IS  - 1872-7549 (Electronic)
IS  - 0166-4328 (Linking)
VI  - 264
DP  - 2014 May 1
TI  - mTOR and autophagy in normal brain aging and caloric restriction ameliorating 
      age-related cognition deficits.
PG  - 82-90
LID - S0166-4328(14)00072-2 [pii]
LID - 10.1016/j.bbr.2014.02.005 [doi]
AB  - Defect of autophagy is common to many neurodegenerative disorders because it 
      serves as a major degradation pathway for the clearance of various 
      aggregate-prone proteins. Mammalian target of rapamycin (mTOR) signaling, which 
      is recognized as the most important negative regulator of autophagy, is also 
      involved in neurodegenerative diseases. However, the role of mTOR and its 
      dependent autophagy in normal brain during aging remains unknown. Furthermore, 
      caloric restriction (CR) is frequently used as a tool to study mechanisms behind 
      aging and age-associated diseases because CR can prevent age-related diseases and 
      prolong lifespan in several model organisms. Inhibiting mTOR and promoting 
      autophagy activity play roles in aging delayed by CR. However, whether CR can 
      ameliorate age-related cognition deficits by inhibiting mTOR and activate 
      autophagy in hippocampus needs to be further investigated. Here we showed a 
      decline of autophagic degradation in mice hippocampus in correlation with 
      age-dependent cognitive dysfunction, whereas the activity of mTOR and its 
      upstream brain-derived neurotrophic factor (BDNF)/phosphatidylinositide 3-kinase 
      (PI3K)/protein kinase B (Akt) signaling was decreased with aging. In addition, 
      facilitating the mTOR pathway successfully declines and sustains autophagic 
      degradation with aging in hippocampus by CR treatment and is involved in CR by 
      ameliorating age-related cognitive deficits.
CI  - Copyright (c) 2014 Elsevier B.V. All rights reserved.
FAU - Yang, Fengying
AU  - Yang F
AD  - Department of Rehabilitation and Sports Medicine, Tianjin Medical University, 
      Tianjin 300070, China.
FAU - Chu, Xiaolei
AU  - Chu X
AD  - Department of Rehabilitation, Tianjin Hospital, Tianjin 300211, China.
FAU - Yin, Miaomiao
AU  - Yin M
AD  - Department of Rehabilitation, Tianjin Huanhu Hospital, Tianjin 300060, China.
FAU - Liu, Xiaolei
AU  - Liu X
AD  - Department of Rehabilitation and Sports Medicine, Tianjin Medical University, 
      Tianjin 300070, China.
FAU - Yuan, Hairui
AU  - Yuan H
AD  - Department of Rehabilitation and Sports Medicine, Tianjin Medical University, 
      Tianjin 300070, China.
FAU - Niu, Yanmei
AU  - Niu Y
AD  - Department of Rehabilitation and Sports Medicine, Tianjin Medical University, 
      Tianjin 300070, China.
FAU - Fu, Li
AU  - Fu L
AD  - Department of Rehabilitation and Sports Medicine, Tianjin Medical University, 
      Tianjin 300070, China; Department of Physiology, School of Medicine, Tianjin 
      Medical University, Tianjin 300070, China. Electronic address: lifu@tijmu.edu.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140210
PL  - Netherlands
TA  - Behav Brain Res
JT  - Behavioural brain research
JID - 8004872
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - EC 2.7.1.137 (Phosphatidylinositol 3-Kinase)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Age Factors
MH  - *Aging
MH  - Animals
MH  - Autophagy/*physiology
MH  - Brain/*metabolism
MH  - Brain-Derived Neurotrophic Factor/metabolism
MH  - Caloric Restriction/*methods
MH  - Cognition Disorders/diet therapy/*therapy
MH  - Disease Models, Animal
MH  - Food Deprivation
MH  - Gene Expression Regulation
MH  - Male
MH  - Maze Learning
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Phosphatidylinositol 3-Kinase/metabolism
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Signal Transduction
MH  - Sirolimus/*metabolism
MH  - Time Factors
OTO - NOTNLM
OT  - Autophagy
OT  - Caloric restriction
OT  - Cognition
OT  - Hippocampus
OT  - Mammalian target of rapamycin
EDAT- 2014/02/15 06:00
MHDA- 2014/11/06 06:00
CRDT- 2014/02/15 06:00
PHST- 2013/11/21 00:00 [received]
PHST- 2014/01/31 00:00 [revised]
PHST- 2014/02/04 00:00 [accepted]
PHST- 2014/02/15 06:00 [entrez]
PHST- 2014/02/15 06:00 [pubmed]
PHST- 2014/11/06 06:00 [medline]
AID - S0166-4328(14)00072-2 [pii]
AID - 10.1016/j.bbr.2014.02.005 [doi]
PST - ppublish
SO  - Behav Brain Res. 2014 May 1;264:82-90. doi: 10.1016/j.bbr.2014.02.005. Epub 2014 
      Feb 10.