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

J Neurosci
Authors
Keywords
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.

Year of Publication
2013
Journal
J Neurosci
Volume
33
Issue
21
Pages
8951-60
Date Published
2013 May 22
ISSN
1529-2401
URL
DOI
10.1523/JNEUROSCI.5657-12.2013
PubMed ID
23699506
PubMed Central ID
PMC3775567
Links
Grant list
P01 AG027916 / AG / NIA NIH HHS / United States
P01AG027916 / AG / NIA NIH HHS / United States
Howard Hughes Medical Institute / United States