Some organs age faster. Hidden DNA damage is to blame –

Some organs age faster. Hidden DNA damage is to blame

Cells that divide poorly, such as those in the liver, accumulate mutations in non-coding parts of the genome, where the sites for starting DNA replication are located.

Left: in red, liver cells with damaged DNA. Right: In yellow, proliferating intestinal cells, whose DNA is not damaged.
Image: UNIGE / UNIBE.

Tissue aging is, in general, explained by the accumulation of genetic mutations in cells. However, some organs, such as the liver and kidneys, age more quickly than the skin or intestines, for example. In an article published on September 17 in the journal CellThanos Halazonetis, professor in the Department of Molecular and Cellular Biology (Faculty of Science), and his colleagues reveal a mechanism capable of explaining this difference. A mechanism which is hidden in the non-coding part of the genome, that is to say the regions of DNA involved in processes of regulation or organization of the genome but which do not contain a gene coding for proteins. Going more easily unnoticed and escaping DNA repair systems, random damage that occurs in these “silent” regions accumulates more than in other regions of the genome. Biologists have just discovered in mice that it is also in these non-coding parts that the “start sites for DNA replication” are located. They are therefore exposed to an increased risk of random mutations, especially in so-called “low cell proliferation” tissues, that is to say those whose cells divide very little, such as those of the liver or kidneys, precisely. This damage ultimately prevents DNA replication and therefore cell division. This has the effect of allowing an additional accumulation of mutations and accelerating the aging process.