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A team with participation of the Consejo Superior de Investigaciones Científicas (CSIC), described in a model plant molecular mechanism that prevents the body from inheriting epigenetic alterations of the DNA of their parents. These alterations in the genome of different genetic mutations and involved in the development of different diseases may arise from exposure of DNA to the external environment over the years. Confirmed the presence of similar processes in mammals, the finding would help to understand why some diseases, especially cancer, its incidence increases with age.
The findings are published in Science.

The work product of an international collaboration, with the participation of researchers of the CSIC Mario Fernández Fraga, National Center for Biotechnology (CSIC) in Madrid, as well as that of Mary Berdasco and Manel Esteller of the Institute of Biomedical Research Bellvitge-Institut Català d'Oncologia (ICO-IDIBELL) and researcher of the Catalan Institution for Research and Advanced Studies (ICREA), Barcelona.

In addition to gene mutations, changes in DNA sequence that occur unexpectedly and can be inherited, the genome may experience other changes without changing the genetic code, make a particular gene is expressed or not.

This second type of disturbance, the epigenetic, are more affected by external factors such as diet. "We can imagine that our genome is the alphabet of our cells, but who gives meaning to provide its spelling is the epigenome, thanks to various chemical modifications, particularly DNA methylation" says Manel Esteller. He adds: "The plant Arabidopsis thaliana (a model used at work) and humans share some of that common epigenetic, and we can do in the first experiments to understand the epigenetic mechanisms, which would be impossible in people. "

"The study of epigenetic alterations is relevant for understanding issues such as development, growth and aging of an organism. But also because these changes could jeopardize the health, and that epigenetic changes are a major cause of cancer, as well as being behind other diseases, "says Fernández Fraga.

CSIC researcher uses one of the clearest examples of the impact of this discipline: "The epigenetics is fundamental to explain why two twins with identical DNA, are phenotypic differences, however small they are."

The work published by the journal Science that seeks to clarify one of the unresolved mysteries of physics: how epigenetic patterns are maintained through successive generations, ie, why the DNA does not inherit epigenetic changes that accumulate over predecessors of life?

"This is an important issue because during the development of an organism can accumulate epigenetic errors that, if passed on to successive generations, can engage the new body," says Fernandez Fraga.

CSIC researcher extends this idea: "An example of these errors could be the epigenetic mechanism involved in the global loss of methylation with age. One of the most frequent epigenetic alterations in human cancer is precisely this shortcoming. If inherited , could lead to negative consequences for the organism. "

The research describes a molecular mechanism that could help to understand the enigma: the process, observed in an experimental model, repairs caused epigenetic alterations in previous generations and, therefore, restores the correct epigenetic patterns in a new body. The next step for researchers should be to ascertain whether similar mechanisms exist in mammals. According to researchers at the CSIC, confirmed this fact, the finding would have relevance in many respects.

Thus, among other things, help to understand why some diseases such as cancer cases are increasing in number with age. "The tumors originate mainly because of errors not only genetic but also epigenetic. The risk of developing increases with age, as there is more time to accumulate this type of molecular errors or less able to repair them," he explains Fraga.

The possibility of epigenetic diseases associated with age in young individuals would be less because mechanisms as described in this paper help to restore normal epigenetic patterns in the new organization. "Also we know that the epigenetic inactivation of genes associated with aging, as in Werner's syndrome is associated with the development of human tumors," says Manel Esteller.

To verify the existence of this mechanism, the authors studied the patterns of DNA methylation in successive generations of crosses of plants deficient enzyme methylated DNA and normal plants. Found that the normal patterns of methylation were gradually recovering, thanks to the action of a special type of RNA interference, directed specifically against methylation of repetitive sequences.