A Dietary Regimen of Caloric Restriction or Pharmacological Activation of SIRT1 to Delay the Onset of Neurodegeneration
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8951.full.pdf
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Author(s)
Graeff, Johannes
Kahn, Martin
Samiei, Alireza
Gao, Jun
Ota, Kristie
Rei, Damien
Tsai, Li-Huei
Date Issued
May 2013
Journal
Journal of Neuroscience
Publisher
Society for Neuroscience
Citation
Graff, J. et al. “A Dietary Regimen of Caloric Restriction or Pharmacological Activation of SIRT1 to Delay the Onset of Neurodegeneration.” Journal of Neuroscience 33, 21 (May 2013): 8951–8960 © 2013 The Authors
Version
Final published version
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.
MIT Department
Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences
Picower Institute for Learning and Memory
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Creative Commons Attribution 4.0 International License
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DOI of Published Version
https://doi.org/10.1523/JNEUROSCI.5657-12.2013
