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.
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.
Schmelzer
Constance
C
Institute of Human Nutrition and Food Science, Molecular Prevention, Christian-Albrechts-University of Kiel, Heinrich-Hecht-Platz 10, Kiel, Germany.
Kubo
Hiroshi
H
Mori
Masayuki
M
Sawashita
Jinko
J
Kitano
Mitsuaki
M
Hosoe
Kazunori
K
Boomgaarden
Inka
I
Döring
Frank
F
Higuchi
Keiichi
K
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
D047493:PPAR alpha; D014451:Ubiquinone; C024989:coenzyme Q10