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.
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