title: The daily rhythms of mitochondrial gene expression and oxidative stress regulation are altered by aging in the mouse liver.
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 Clock(Δ19) 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.
authors.affiliation: a State Key Laboratory of Virology, College of Life Sciences, Wuhan University , Wuhan, Hubei Province , P.R. China and.
authors.forename: Changxia
authors.initials: C
authors.lastname: Gong
authors.affiliation: a State Key Laboratory of Virology, College of Life Sciences, Wuhan University , Wuhan, Hubei Province , P.R. China and.
authors.forename: Chengwei
authors.initials: C
authors.lastname: Li
authors.affiliation: a State Key Laboratory of Virology, College of Life Sciences, Wuhan University , Wuhan, Hubei Province , P.R. China and.
authors.forename: Xiaoqing
authors.initials: X
authors.lastname: Qi
authors.affiliation: a State Key Laboratory of Virology, College of Life Sciences, Wuhan University , Wuhan, Hubei Province , P.R. China and.
authors.forename: Zhiyin
authors.initials: Z
authors.lastname: Song
authors.affiliation: a State Key Laboratory of Virology, College of Life Sciences, Wuhan University , Wuhan, Hubei Province , P.R. China and.
authors.forename: Jianguo
authors.initials: J
authors.lastname: Wu
authors.affiliation: b Department of Biology , University of Missouri-St. Louis . St. Louis, MO , USA.
authors.forename: Michael E
authors.initials: ME
authors.lastname: Hughes
authors.affiliation: a State Key Laboratory of Virology, College of Life Sciences, Wuhan University , Wuhan, Hubei Province , P.R. China and.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Li
mesh_terms: D000367:Age Factors; D000375:Aging / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D056926:CLOCK Proteins / Q000235:genetics / Q000378:metabolism; D057906:Circadian Clocks / Q000235:genetics; D002940:Circadian Rhythm / Q000235:genetics; D004272:DNA, Mitochondrial / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D005838:Genotype; D008099:Liver / Q000378:metabolism*; D008297:Male; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008930:Mitochondria, Liver / Q000378:metabolism*; D023421:Models, Animal; D009154:Mutation; D018384:Oxidative Stress / Q000235:genetics; D010641:Phenotype; D017382:Reactive Oxygen Species / Q000378:metabolism; D013997:Time Factors
chemical_list: D004272:DNA, Mitochondrial; D017382:Reactive Oxygen Species; D056926:CLOCK Proteins; C538944:Clock protein, mouse
keywords: Aging; circadian rhythms; mitochondria; oxidative stress