Creatine supplementation normalizes mutagenesis of mitochondrial DNA as well as functional consequences.

• Abstract: Mutations of mitochondrial (mt) DNA play a role in neurodegeneration, normal aging, premature aging of the skin (photoaging), and tumors. We and others could demonstrate that mtDNA mutations can be induced in skin cells in vitro and in normal human skin in vivo by repetitive, sublethal ultraviolet (UV)-A-irradiation. These mutations are mediated by singlet oxygen and persist in human skin as long-term biomarkers of UV exposure. Although mtDNA exclusively encodes for the respiratory chain, involvement of the energy metabolism in mtDNA mutagenesis and a protective role of the energy precursor creatine have thus far not been shown. We assessed the amount of a marker mutation of mtDNA, the so-called common deletion, by real-time PCR. Induction of the common deletion was paralleled by a measurable decrease of oxygen consumption, mitochondrial membrane potential, and ATP content, as well as an increase of matrix metalloproteinase-1. Mitochondrial mutagenesis as well as functional consequences could be normalized by increasing intracellular creatine levels. These data indicate that increase of the energy precursor creatine protects from functionally relevant, aging-associated mutations of mitochondrial DNA.
• Authors: Mark Berneburg, Tobias Gremmel, Viola Kürten, Peter Schroeder, Ines Hertel, Anna von Mikecz, Susanne Wild, Min Chen, Lieve Declercq, Mary Matsui, Thomas Ruzicka, Jean Krutmann (Affiliation: Molecular Oncology and Aging, Department of Dermatology, Eberhard Karls University, Tuebingen, Germany.)
• Journal: The Journal of investigative dermatology (J Invest Dermatol) Vol. 125 Issue 2 Pg. 213-20 (Aug 2005) ISSN: 0022-202X [Print] United States
• PMID: 16098029 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antioxidants
• Carbon Radioisotopes
• DNA, Mitochondrial
• Adenosine Triphosphate
• Creatine
• Matrix Metalloproteinase 1

Topics

• Adenosine Triphosphate (metabolism)
• Antioxidants (pharmacokinetics, pharmacology)
• Carbon Radioisotopes (diagnostic use)
• Cells, Cultured
• Creatine (pharmacokinetics, pharmacology)
• DNA, Mitochondrial (genetics)
• Electron Transport (genetics)
• Energy Metabolism (drug effects)
• Fibroblasts (cytology, physiology)
• Humans
• Matrix Metalloproteinase 1 (metabolism)
• Membrane Potentials (drug effects)
• Mitochondria (drug effects, genetics)
• Mutagenesis (drug effects, radiation effects)
• Oxygen Consumption (drug effects, radiation effects)
• Skin (cytology)
• Skin Aging (drug effects, radiation effects)
• Ultraviolet Rays (adverse effects)