title: Supplementation with the reduced form of Coenzyme Q10 decelerates phenotypic characteristics of senescence and induces a peroxisome proliferator-activated receptor-alpha gene expression signature in SAMP1 mice.
abstract: Our present study reveals significant decelerating effects on senescence processes in middle-aged SAMP1 mice supplemented for 6 or 14 months with the reduced form (Q(10)H(2), 500 mg/kg BW/day) of coenzyme Q(10) (CoQ(10)). To unravel molecular mechanisms of these CoQ(10) effects, a genome-wide transcript profiling in liver, heart, brain and kidney of SAMP1 mice supplemented with the reduced (Q(10)H(2)) or oxidized form of CoQ(10) (Q(10)) was performed. Liver seems to be the main target tissue of CoQ(10) intervention, followed by kidney, heart and brain. Stringent evaluation of the resulting data revealed that Q(10)H(2) has a stronger impact on gene expression than Q(10), primarily due to differences in the bioavailability. Indeed, Q(10)H(2) supplementation was more effective than Q(10) to increase levels of CoQ(10) in the liver of SAMP1 mice. To identify functional and regulatory connections of the "top 50" (p<0.05) Q(10)H(2)-sensitive transcripts in liver, text mining analysis was used. Hereby, we identified Q(10)H(2)-sensitive genes which are regulated by peroxisome proliferator-activated receptor-alpha and are primarily involved in cholesterol synthesis (e.g. HMGCS1, HMGCL and HMGCR), fat assimilation (FABP5), lipoprotein metabolism (PLTP) and inflammation (STAT-1). These data may explain, at least in part, the decelerating effects on degenerative processes observed in Q(10)H(2)-supplemented SAMP1 mice.
authors: Institute of Human Nutrition and Food Science, Molecular Prevention, Christian-Albrechts-University of Kiel, Heinrich-Hecht-Platz 10, Kiel, Germany.
authors: Constance
authors: C
authors: Schmelzer
authors: Hiroshi
authors: H
authors: Kubo
authors: Masayuki
authors: M
authors: Mori
authors: Jinko
authors: J
authors: Sawashita
authors: Mitsuaki
authors: M
authors: Kitano
authors: Kazunori
authors: K
authors: Hosoe
authors: Inka
authors: I
authors: Boomgaarden
authors: Frank
authors: F
authors: Döring
authors: Keiichi
authors: K
authors: Higuchi
mesh_terms: D000375:Aging / Q000187:drug effects*; D000818:Animals; D019587:Dietary Supplements; D004435:Eating / Q000187:drug effects; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D008099:Liver / Q000378:metabolism; D051379:Mice; D010084:Oxidation-Reduction; D047493:PPAR alpha / Q000235:genetics*; D010641:Phenotype; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology
chemical_list: D047493:PPAR alpha; D014451:Ubiquinone; C024989:coenzyme Q10