Epigenetic regulation in aging and inflammation and consequences of intervention with EGCG, equol and Vitamin E

Autoren:Pointner, Angelika; Gessner, Diana Saskia Franziska; Zappe, Katja; Remely, Marlene; Magnet, Ulrich; Haslberger, Alexander
Abstrakt:In many complex diseases or ageing linked health problems a low grade inflammation, oxidative damage of DNA, epigenetic misregulation are known. Especially changes in the epigenetic regulation of gene expression have been identified as central mechanisms in the development of age-related diseases. Increasing evidence shows that the aging process is associated with the accumulation of reactive oxygen species (ROS). A constant high level of oxidative stress may lead to alterations in methylation status of DNA repair genes and consequently cause DNA instability, particularly in microsatellite DNA, which are short repetitive DNA sequences. Microsatellite instability is linked with telomere shortening and a dysregulation of DNA repair mechanisms.Epigenetic effects of plant ingredients epigallocatechine gallate (EGCG), equol and Vitamin E were analysed for epigenetic regulation of CpG promotor methylation of genes involved in inflammation, DNA repair and ageing as well as telomere length and telomerase activity in primary fibroblasts and cancer cell line Caco-2. With EGCG we see effects on the promotor methylation of IL6, DNA mismatch repair protein MLH1 as well as a reduction of telomere length and decreased telomerase activity in Caco 2 cells. In contrast we observed an increased telomere length and methylation of 3 CpGs in the promoter region of TERT in fibroblasts. Furthermore EGCG is even able to counteract in a dose dependent manner the H2O2 induced increase of MLH1 mRNA expression.These results and further preliminary results indicate that EGCG reduces dose dependent oxidative damage and therefore cells require less MLH1. Intervention with plant ingredients on the epigenetic regulation is a promising approach to interfere in numerous complex diseases and epigenetic methylation provides valid markers in personalized nutrition, prevention and disease control. Epigenetics are seen as a important link between nutrition and health and can be used to prevent or even treat several diseases.