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J Neurosci. 2013 May 22;33(21):8951-60. doi: 10.1523/JNEUROSCI.5657-12.2013.

A dietary regimen of caloric restriction or pharmacological activation of SIRT1 to delay the onset of neurodegeneration.

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  • 1Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences and Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.

Abstract

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.

PMID:
23699506
[PubMed - indexed for MEDLINE]
PMCID:
PMC3775567
Free PMC Article

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