Aging and the circadian clock
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AGING AND THE CIRCADIAN CLOCK. DENNIE KIM MCB186 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 ?.

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Aging and the circadian clock

AGING AND THE CIRCADIAN CLOCK

DENNIE KIMMCB18613 DECEMBER 2006


Levels of control
LEVELS OF CONTROL

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


Cr sirt1 and neuronal cell survival
CR, SIRT1, and NEURONAL CELL SURVIVAL

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


Deterioration of biological rhythms
DETERIORATION OF BIOLOGICAL RHYTHMS

NEURODEGENERATION ?

Bentivoglio et al. 2006


Deterioration of biological rhythms1
DETERIORATION OF BIOLOGICAL RHYTHMS

Hofman et al., 2006


Not just in the scn
NOT JUST IN THE SCN?

M. HOFMAN, 2000.


Cr induced lifespan extension and neuronal rescue
CR-INDUCED LIFESPAN EXTENSION- and -NEURONAL RESCUE?


Hypothesis 1 cr mice are protected from degeneration of rhythmicity
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
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
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.


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