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(20-07-16) World's longest living rats have 'extraordinary' resistance to cancer


by Jonathan Benson, staff writer

Japanese scientists may have just discovered the fountain of youth, but perhaps in the least-likely of places: rats. A collaborative team of researchers from Hokkaido and Keio Universities appears to be one step closer to understanding precisely how cancer develops, after identifying a unique anti-cancer mechanism in naked mole-rats (NMRs), which almost never develop cancer and live far longer than other types of rats.

The cohort carefully evaluated NMRs, which live upwards of 30 years – about 10 times longer than normal mice – to see what differs in their genetic and cellular makeup to make them less prone to cancer. Members of the team described what they say are these animals' "extraordinary" resistance to cancer, which they believe could lead to some major advancements in the way cancer is prevented and treatedin humans.

To conduct their evaluation, the scientists took samples of skin fibroblast tissue from adult NMRs and reprogrammed individual cells to become pluripotent stem cells, or iPSCs, the "i" indicating that these stem cells were induced. Pluripotent stem cells, as you may already know, are a type of undifferentiated "master" cell capable of developing into all forms of adult cell types, depending on what the body needs.

Typically, iPSCs from humans and other types of mice are potentially tumorous, which is why their use as a medical treatment remains somewhat controversial. But in NMRs, iPSCs don't cause tumors due to a special tumor-suppressor gene known as alternative reading frame, or ARF, that remains activated in NMRs. In humans and in other mice, ARF remains suppressed under normal conditions, altering the expression of these otherwise life-giving cells.

NMRs also possess a mutated and dysfunctional gene known as ERAS that, when functional, has tumorigenic properties. This combined with ARF activation is believed to be why NMRs are almost entirely immune to developing cancer, a theory that was further confirmed by experiments in which scientists altered the ARF gene in NMRs to be dysfunctional, as well as forced the expression of ERAS; when these altered genes were inserted into test mice, those mice grew exceptionally large tumors that they otherwise wouldn't have developed.

At the same time, when researchers suppressed the ARF gene in mole-rat cells during the process of reprogramming them into iPSCs, these same cells showed signs of cellular senescence, and they also stopped proliferating. This ARF suppression-induced senescence (ASIS), researchers believe, is what further protects NMRs from developing cancerous tumors, and this protection is unique to NMRs.

"Further research into the detailed mechanisms underlying ASIS in naked mole-rats may shed new light on cancer resistance in the mole-rats and contribute to the generation of non-tumorigenic human-iPSCs, enabling safer cell-based therapeutics," Kyoko Miura, an assistant professor at Hokkaido University, commented about the findings.

Hyaluronic acid also linked to amazing anti-cancer nature of mole rats
Earlier research published in the journal Nature investigated other curious characteristics of NMRs, including their inability to be burned by acid or feel the "hot" taste of chili peppers. Researchers dubbed these creatures "freaks of nature," adding that these mammals secrete a special sugary substance known as hyaluronic acid (HA) that scientists believe protects these animals' cells from developing tumors.

The paper describes HA as an anti-cancer substance that nips "'pre-cancers' in the bud," further adding to the intrigue of these amazingly unusual creatures.

"In tissue-culture experiments, the cells of naked mole rats could be made cancerous by blocking the gene that encodes HA or by increasing levels of a protein that recycles the sugar," Nature coverage of this earlier study reported.

A summary of that paper can be accessed here.


Sources for this article include:

ScienceDaily.com

Nature.com

Science.NaturalNews.com


Fonte: NaturalNews

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