Differential modulation of clock gene expression in the suprachiasmatic nucleus, liver and heart of aged mice

Abstract

Studies on the molecular clockwork during aging have been hitherto addressed to core clock genes. These previous investigations indicate that circadian profiles of core clock gene expression at an advanced age are relatively preserved in the master circadian pacemaker and the hypothalamic suprachiasmatic nucleus (SCN), and relatively impaired in peripheral tissues. It remains to be clarified whether the effects of aging are confined to the primary loop of core clock genes, or also involve secondary clock loop components, including Rev-erbα and the clock-controlled genes Dbp and Dec1. Using quantitative real-time RT-PCR, we here report a comparative analysis of the circadian expression of canonical core clock genes (Per1, Per2, Cry1, Cry2, Clock and Bmal1) and non-core clock genes (Rev-erbα, Dbp and Dec1) in the SCN, liver, and heart of 3month-old vs 22month-old mice. The results indicate that circadian clock gene expression is significantly modified in the SCN and peripheral oscillators of aged mice. These changes are not only highly tissue-specific, but also involve different clock gene loops. In particular, we here report changes of secondary clock loop components in the SCN, changes of the primary clock loop in the liver, and minor changes of clock gene expression in the heart of aged mice. The present findings outline a track to further understanding of the role of primary and secondary clock loop components and their crosstalk in the impairment of circadian output which characterizes aging.

Keywords: Aging; Bmal1; Circadian pacemaker; Cryptochrome genes; Dbp; Dec1; Period genes; Peripheral oscillators; Rev-erbα.