Resetting of central and peripheral circadian oscillators in aged rats.

The mammalian circadian timing system is affected by aging. Analysis of the suprachiasmatic nucleus (SCN) and of other circadian oscillators reveals age-related changes which are most profound in extra-SCN tissues. Some extra-SCN oscillators appear to stop oscillating in vivo or display altered phase relationships. To determine whether the dynamic behavior of circadian oscillators is also affected by aging we studied the resetting behavior of the Period1 transcriptional rhythm of peripheral and central oscillators in response to a 6h advance or delay in the light schedule. We employed a transgenic rat with a luciferase reporter to allow for real-time measurements of transcriptional rhythmicity. While phase resetting in the SCN following an advance or a delay of the light cycle appears nearly normal in 2-year-old rats, resynchronization of the liver was seriously disrupted. In addition, the arcuate nucleus and pineal gland exhibited faster resetting in aged rats relative to 4-8-month-old controls. The consequences of these deficits are unknown, but may contribute to organ and brain diseases in the aged as well as the health problems that are common in older shift-workers.