Principal Investigator Leonard Guarente
Co-investigator H Horvitz
Along with modulating nutritive aspects of mammalian physiology, SIRT1 has been implicated in the function of circadian rhythms. Circadian clock-controlled rhythms are responsible for maintaining temporal programming that is essential for behavioral and physiological coordination. We have recently demonstrated that SIRT1 in the brain directs the central circadian clock by regulating transcription of BMAL1 and CLOCK, two crucial components modulating circadian rhythms. Importantly, the normal decay in the function of the central circadian clock with aging can be suppressed by over-expression of SIRT1 in the brain. This signifies an important role for SIRT1 in chronomodulation that may have implications for aging and other age-related disorders, including cancer and metabolic syndrome.