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CNIO researchers discover a gene that links stem cells, aging and cancer

ore in depth the role of Sox4 in the adult organism.

It was not an easy task, because mice in which Sox4 had been eliminated die before birth. The authors' working strategy consisted of generating a line of mice that do express Sox4, but at lower quantities than normal.

These animals survive and are fertile, but they have several peculiarities: they are smaller than normal, age earlier and do not have cancer. Conversely, they do develop other age-related illnesses.

As stated by the researchers, the mice with less Sox4: "show signs of premature loss of tissue homeostasis (maintenance), shorter telomeres, and, as a consequence, accelerated ageing and the appearance of pathologies associated with ageing, as well as cancer resistance."

The mice deficient in Sox4 have, for example, little bone regeneration and lots of osteoporosis, indicating that this gene is important for the bone tissue maintenance mechanism.

But the authors wanted to especially investigate whether stem cells were the key actors in these consequences of lowering Sox4 levels. To this end, they created more mice in which this gene was completely deactivated in hair follicle stem cells; those responsible for the regeneration of the epidermis. In these mice, precisely, the skin repair mechanism did not work, the skin aged prematurely and they did not develop skin cancer.

The puzzle has not yet been solved: why these animals are less likely to have cancer?. One possible explanation is that a lower rate of tissue regeneration given than the stem cells are less active in the absence of Sox4 is a cancer-inhibiting mechanism.

As Maria Blasco, the co-author, says: "this would imply that the origin of cancer is associated to regeneration errors, and if there is less regeneration there is also less cancer. The negative side is that less renewal also means more ageing. It is a complex balance, which we will only understand with more research."

Contact: Nuria Noriega
Centro Nacional de Investigaciones Oncologicas (CNIO)

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CNIO researchers discover a gene that links stem cells, aging and cancer
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