1. AGING AND THE CIRCADIAN CLOCK DENNIE KIM MCB186 13 DECEMBER 2006

2. LEVELS OF CONTROL CHOU ET AL., 2003. J. NEURO 23(33)

3. CR, SIRT1, and NEURONAL CELL SURVIVAL B.L. Tang, 2006. Neurobiology of Aging 27 (503)

4. DETERIORATION OF BIOLOGICAL RHYTHMS NEURODEGENERATION ? Bentivoglio et al. 2006

5. DETERIORATION OF BIOLOGICAL RHYTHMS Hofman et al., 2006

6. NOT JUST IN THE SCN? M. HOFMAN, 2000.

7. CR-INDUCED LIFESPAN EXTENSION - and - NEURONAL RESCUE?

8. Hypothesis 1: CR mice are protected from degeneration of rhythmicity. Calorie restrict mice CONTROL(S): NORMAL DIET MOUSE, RESVERATROL-TREATED MOUSE, SIRT1-K/O MOUSE Measure rhythms/neuronal activity Test entrainment

9. Hypothesis 2: Deterioration of Circadian Clock is a Problem of Neurodegeneration If neurons of the SCN (or DMH/VLPO) die during aging, the number of connections made should decrease. Use retrograde/anterograde tracers to label neuronal connections in young and old mice. Similarly, compare old mice to CR “old” mice.

10. Hypothesis 3: SIRT1 Activation in SCN Neurons Can Prevent Circadian Dysfunction. Create an temporally/transiently SIRT1-inducible transgenic mouse. Measure rhythms/SCN-neuronal activity compared to wt mouse. Western blot/In situ hybridization/Immunohistochemistry to show increased levels of SIRT1 in transgenic mouse.