RT Journal Article
SR Electronic
T1 A Dietary Regimen of Caloric Restriction or Pharmacological Activation of SIRT1 to Delay the Onset of Neurodegeneration
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 8951
OP 8960
DO 10.1523/JNEUROSCI.5657-12.2013
VO 33
IS 21
A1 Gräff, Johannes
A1 Kahn, Martin
A1 Samiei, Alireza
A1 Gao, Jun
A1 Ota, Kristie T.
A1 Rei, Damien
A1 Tsai, Li-Huei
YR 2013
UL http://www.jneurosci.org/content/33/21/8951.abstract
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.