[Enzymatic DNA methylation as an aging mechanism].
By analysis of 70 functional parameters of organism it has been shown that the senescence of human organs starts from the age of 20 +/- 10 years and it has more or less a linear character in the most cases. Judging by the averaged aging rate, human maximal lifespan can be equal to about 145 years. An aging model has been proposed according to it the functional involution is caused by cells destructing and is a result of gradual accumulation of special mutations in genome. The evidences has been obtained that enzymatic DNA methylation is a powerful generator for the 5mC-->T+C transition, constantly occurring with each cell division. It has been found that the age-related loss of the most part or all 5mC residues from DNA coincides with both the Hayflick limit in cell lines and the maximal lifespan of different animal species studied. The rate of DNA hypomethylation is proportional to the cell aging rate in vitro and in vivo. The 5mC-->T transitions contribute more than half of all point mutations, accumulated in genome of vertebrates during evolution. These substitutions occur ten times more often in the methylated sites than in other positions of DNA and they disproportional contribute to the general mutagenesis and to the hereditary human diseases. The conclusion has been made that DNA methylation meet the requirements of the main criterions of an aging biomarker and it can be considered as a mechanism for genetically programmed accumulation of mutations with aging. In immortal cell lines this mechanism starts working in the reverse direction, increasing the 5mC content in DNA.
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D000375:Aging / Q000378:metabolism*; D015415:Biomarkers; D004247:DNA / Q000378:metabolism*; D006801:Humans; D008745:Methylation; D009154:Mutation; D014407:Tumor Cells, Cultured
D015415:Biomarkers; D004247:DNA
Enzimaticheskoe metilirovanie DNK kak mekhanizm stareniia.