Partial depletion of mitochondrial DNA from human skin fibroblasts induces a gene expression profile reminiscent of photoaged skin.

In photoaged skin, wrinkles result from an increased degradation and a decreased de novo synthesis of collagen fibers. At the molecular level, photoaged skin is characterized by increased amounts of large-scale deletions of the mitochondrial (mt) genome such as the 4,977 bp common deletion. The common deletion can be generated in dermal fibroblasts through repetitive ultraviolet (UV) A irradiation, and this was found to be associated with an increased expression of the collagen-degrading enzyme matrix metalloproteinase-1 (MMP-1).

Six genes associated with the clinical phenotypes of individuals with deficient and proficient DNA repair.

Xeroderma pigmentosum (XP) is a genetic disorder characterised by hypo-/hyperpigmentation, increased sensitivity to ultraviolet (UV)-radiation and an up to 2000-fold increased skin cancer risk. Cells from XP-patients are defective in nucleotide excision repair (NER) responsible for repair of UV-induced DNA damage. This defect accounts for their mutator phenotype but does not predict their increased skin cancer risk.

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

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.