The daily rhythms of mitochondrial gene expression and oxidative stress regulation are altered by aging in the mouse liver

Changxia Gong, Chengwei Li, Xiaoqing Qi, Zhiyin Song, Jianguo Wu, Michael E. Hughes, Xiaodong Li

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

Abstract

The circadian clock regulates many cellular processes, notably including the cell cycle, metabolism and aging. Mitochondria play essential roles in metabolism and are the major sites of reactive oxygen species (ROS) production in the cell. The clock regulates mitochondrial functions by driving daily changes in NAD+ levels and Sirt3 activity. In addition to this central route, in the present study, we find that the expression of some mitochondrial genes is also rhythmic in the liver, and that there rhythms are disrupted by the ClockΔ19 mutation in young mice, suggesting that they are regulated by the core circadian oscillator. Related to this observation, we also find that the regulation of oxidative stress is rhythmic in the liver. Since mitochondria and ROS play important roles in aging, and mitochondrial functions are also disturbed by aging, these related observations prompt the compelling hypothesis that circadian oscillators influence aging by regulating ROS in mitochondria. During aging, the expression rhythms of some mitochondrial genes were altered in the liver and the temporal regulation over the dynamics of mitochondrial oxidative stress was disrupted. However, the expression of clock genes was not affected. Our results suggested that mitochondrial functions are combinatorially regulated by the clock and other age-dependent mechanism(s), and that aging disrupts mitochondrial rhythms through mechanisms downstream of the clock.

Original languageEnglish
Pages (from-to)1254-1263
Number of pages10
JournalChronobiology International
Volume32
Issue number9
DOIs
StatePublished - Oct 21 2015

Keywords

  • Aging
  • circadian rhythms
  • mitochondria
  • oxidative stress

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