PMID- 23699506
OWN - NLM
STAT- MEDLINE
DCOM- 20130809
LR  - 20220309
IS  - 1529-2401 (Electronic)
IS  - 0270-6474 (Print)
IS  - 0270-6474 (Linking)
VI  - 33
IP  - 21
DP  - 2013 May 22
TI  - A dietary regimen of caloric restriction or pharmacological activation of SIRT1 
      to delay the onset of neurodegeneration.
PG  - 8951-60
LID - 10.1523/JNEUROSCI.5657-12.2013 [doi]
AB  - Caloric restriction (CR) is a dietary regimen known to promote lifespan by 
      slowing down the occurrence of age-dependent diseases. The greatest risk factor 
      for neurodegeneration in the brain is age, from which follows that CR might also 
      attenuate the progressive loss of neurons that is often associated with impaired 
      cognitive capacities. In this study, we used a transgenic mouse model that allows 
      for a temporally and spatially controlled onset of neurodegeneration to test the 
      potentially beneficial effects of CR. We found that in this model, CR 
      significantly delayed the onset of neurodegeneration and synaptic loss and 
      dysfunction, and thereby preserved cognitive capacities. Mechanistically, CR 
      induced the expression of the known lifespan-regulating protein SIRT1, prompting 
      us to test whether a pharmacological activation of SIRT1 might recapitulate CR. 
      We found that oral administration of a SIRT1-activating compound essentially 
      replicated the beneficial effects of CR. Thus, SIRT1-activating compounds might 
      provide a pharmacological alternative to the regimen of CR against 
      neurodegeneration and its associated ailments.
FAU - Graff, Johannes
AU  - Graff J
AD  - Picower Institute for Learning and Memory, Department of Brain and Cognitive 
      Sciences and Howard Hughes Medical Institute, Massachusetts Institute of 
      Technology, Cambridge, Massachusetts 02139, USA.
FAU - Kahn, Martin
AU  - Kahn M
FAU - Samiei, Alireza
AU  - Samiei A
FAU - Gao, Jun
AU  - Gao J
FAU - Ota, Kristie T
AU  - Ota KT
FAU - Rei, Damien
AU  - Rei D
FAU - Tsai, Li-Huei
AU  - Tsai LH
LA  - eng
GR  - P01 AG027916/AG/NIA NIH HHS/United States
GR  - HHMI/Howard Hughes Medical Institute/United States
GR  - P01AG027916/AG/NIA NIH HHS/United States
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Neurosci
JT  - The Journal of neuroscience : the official journal of the Society for 
      Neuroscience
JID - 8102140
RN  - 0 (Cdk5r1 protein, mouse)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Piperidines)
RN  - 0 (Thiazoles)
RN  - 0 (Tumor Suppressor Protein p53)
RN  - 0 (tert-butyl 
      4-((2-(2-(6-(2-(tert-butoxycarbonyl(methyl)amino)ethylamino)-2-butylpyrimidine-4-carboxamido)phenyl)thiazolo(5,4-b)pyridin-6-yl)methoxy)piperidine-1-carboxylate)
RN  - 1406-18-4 (Vitamin E)
RN  - 147336-22-9 (Green Fluorescent Proteins)
RN  - EC 2.7.- (Phosphotransferases)
RN  - EC 2.7.11.1 (Cyclin-Dependent Kinase 5)
RN  - EC 3.5.1.- (Sirt1 protein, mouse)
RN  - EC 3.5.1.- (Sirtuin 1)
RN  - EC 4.2.1.11 (Phosphopyruvate Hydratase)
SB  - IM
MH  - Analysis of Variance
MH  - Animals
MH  - Atrophy/etiology/prevention & control
MH  - Brain/drug effects/pathology/ultrastructure
MH  - Caloric Restriction/*methods
MH  - Case-Control Studies
MH  - Cognition Disorders/etiology/*therapy
MH  - Cyclin-Dependent Kinase 5/genetics
MH  - Disease Models, Animal
MH  - Double-Blind Method
MH  - Excitatory Postsynaptic Potentials/drug effects/physiology
MH  - Female
MH  - Green Fluorescent Proteins/genetics
MH  - Immunoprecipitation
MH  - In Vitro Techniques
MH  - Long-Term Potentiation/genetics/physiology
MH  - Male
MH  - Memory Disorders/etiology/prevention & control
MH  - Mice
MH  - Mice, Transgenic
MH  - Microscopy, Electron, Transmission
MH  - Nerve Tissue Proteins/genetics
MH  - Neurodegenerative Diseases/*complications/pathology
MH  - Phosphopyruvate Hydratase/metabolism
MH  - Phosphotransferases
MH  - Piperidines/therapeutic use
MH  - Silver Staining
MH  - Sirtuin 1/genetics/*metabolism
MH  - Synapses/pathology
MH  - Thiazoles/therapeutic use
MH  - Tumor Suppressor Protein p53/metabolism
MH  - Vitamin E/administration & dosage
PMC - PMC3775567
MID - NIHMS483495
EDAT- 2013/05/24 06:00
MHDA- 2013/08/10 06:00
PMCR- 2013/11/22
CRDT- 2013/05/24 06:00
PHST- 2013/05/24 06:00 [entrez]
PHST- 2013/05/24 06:00 [pubmed]
PHST- 2013/08/10 06:00 [medline]
PHST- 2013/11/22 00:00 [pmc-release]
AID - 33/21/8951 [pii]
AID - 5657-12 [pii]
AID - 10.1523/JNEUROSCI.5657-12.2013 [doi]
PST - ppublish
SO  - J Neurosci. 2013 May 22;33(21):8951-60. doi: 10.1523/JNEUROSCI.5657-12.2013.