Aging and cancer: epigenetics is to blame
It has long been known that age is the main risk factor for the development of many types of malignant tumors. However, the reasons for this are not completely clear. Researchers suggest that one of the mechanisms underlying this phenomenon is DNA methylation, one of the epigenetic mechanisms that regulate gene expression without making changes to the DNA sequence. This process consists in attaching chemical labels – methyl groups – to the DNA chain, which leads to the activation or blocking of the activity of certain genes by changing the interactions between DNA and the intracellular protein synthesis system.
Scientists from the National Institute for the Study of the Sanitary State of the Environment of the USA, Dr. Zongli Xu (Zongli Xu) and Dr. Jack Taylor (Jack Taylor) identified regions of DNA methylation in the human genome that change with age. They also demonstrated that some of the regions, the degree of methylation of which increases significantly with aging, are also characterized by an inadequately high level of methylation in cells of various types of cancer.
These observations were made as a result of the analysis of data obtained during the processing of blood samples collected as part of the Sister Study ("Sister Study"). The purpose of this national-scale study is to attempt to establish the external and genetic causes of breast cancer and other diseases. In total, more than 50,000 women participated in the study, whose sisters were diagnosed with breast cancer.
The authors analyzed blood samples from 1,000 women using microchips analyzing 27,000 specific methylation regions. An age-associated increase in methylation levels was observed in about 30% of the regions. Subsequent comparison of the data obtained with the results of three smaller studies conducted using the same microchips confirmed the revealed pattern for 749 methylation regions. As an additional test, the scientists compared the results with data on methylation of cells of normal tissues and seven different types of malignant tumors contained in the Atlas of the Cancer Genome, a database founded by the National Institute for Cancer Research and the National Institute for Human Genome Research of the USA.
According to Dr. Taylor, DNA methylation is a component of the normal aging process and is characteristic of genes involved in cell development. Malignant cells are often characterized by DNA methylation disorders, however, the authors were surprised by the fact that 70-90% of the regions of increased methylation associated with aging showed high levels of methylation in cells of all seven types of cancer. Taylor suggests that age-related methylation may lead to a decrease in the expression of certain genes, which facilitates the transition of cells to a malignant state.
The authors also determined the normal rate of appearance of age-related regions of increased methylation in the body, which corresponds to the appearance of one such region per year. That is, by the 50th anniversary, 50 regions of increased methylation accumulate in the human genome.
As part of the next phase of the study, the authors plan to analyze a larger number of samples using a newer microchip that allows studying the methylation of 450,000 regions of the genome. As a result, they hope to find out whether environmental influences experienced by a person in childhood and adulthood affect the nature of DNA methylation.
Article Z. Xu et al. Genome-wide age-related DNA methylation changes in blood and other tissues related to histone modification, expression and cancer is published in the journal Carcinogenesis.
Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru based on the materials of the National Institute of Environmental Health Sciences:
NIH Study Offers Insight into Why Cancer Incidence Increases with Age.
05.02.2014