Scientific Publications

A Dietary Regimen of Caloric Restriction or Pharmacological Activation of SIRT1 to Delay the Onset of Neurodegeneration.

Publication TypeJournal Article
AuthorsGräff, J., Kahn M., Samiei A., Gao J., Ota KT, Rei D., and Tsai LH
AbstractCaloric 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 Publication2013
JournalThe Journal of neuroscience : the official journal of the Society for Neuroscience
Volume33
Issue21
Pages8951-60
Date Published (YYYY/MM/DD)2013/05/22
ISSN Number0270-6474
DOI10.1523/JNEUROSCI.5657-12.2013
PubMedhttp://www.ncbi.nlm.nih.gov/pubmed/23699506?dopt=Abstract