AGING AND THE CIRCADIAN CLOCK

DENNIE KIMMCB186

13 DECEMBER 2006

LEVELS OF CONTROL

CHOU ET AL., 2003. J. NEURO 23(33)

CR, SIRT1, and NEURONAL CELL SURVIVAL

B.L. Tang, 2006. Neurobiology of Aging 27 (503)

DETERIORATION OF BIOLOGICAL RHYTHMS

NEURODEGENERATION ?

Bentivoglio et al. 2006

DETERIORATION OF BIOLOGICAL RHYTHMS

Hofman et al., 2006

NOT JUST IN THE SCN?

M. HOFMAN, 2000.

CR-INDUCED LIFESPAN EXTENSION

- and -

NEURONAL RESCUE?

Hypothesis 1: CR mice are protected from degeneration

of rhythmicity.

• Calorie restrict miceCONTROL(S): NORMAL DIET MOUSE, RESVERATROL-TREATED MOUSE, SIRT1-K/O MOUSE

• Measure rhythms/neuronal activity• Test entrainment

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.

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.