Naked mole rats live far longer than similarly sized mammals, and are near immune to cancer. One of the mechanisms of cancer resistance involves the production of a different form of high molecular weight hyaluronan, and much more of it, improving the anti-cancer mechanism of contact inhibition. In addition, other mechanisms derived from changes in hyaluronan may affect life span through improved cellular function, but this is less well explored. Researchers here take the naked mole-rat version of the gene for high molecular weight hyoluronan, hyaluronan synthase 2, and put it into mice. The result is less cancer, improved metabolism, and longer lives.
Naked mole rats are mouse-sized rodents that have exceptional longevity for rodents of their size; they can live up to 41 years, nearly ten times as long as similar-size rodents. Unlike many other species, naked mole rats do not often contract diseases - including neurodegeneration, cardiovascular disease, arthritis, and cancer - as they age. Researchers previously discovered that high molecular weight hyaluronic acid (HMW-HA) is one mechanism responsible for naked mole rats' unusual resistance to cancer. Compared to mice and humans, naked mole rats have about ten times more HMW-HA in their bodies. When the researchers removed HMW-HA from naked mole rat cells, the cells were more likely to form tumors.
The team genetically modified a mouse model to produce the naked mole rat version of the hyaluronan synthase 2 gene, which is the gene responsible for making a protein that produces HMW-HA. While all mammals have the hyaluronan synthase 2 gene, the naked mole rat version seems to be enhanced to drive stronger gene expression. The researchers found that the mice that had the naked mole rat version of the gene had better protection against both spontaneous tumors and chemically induced skin cancer. The mice also had improved overall health and lived longer compared to regular mice. As the mice with the naked mole rat version of the gene aged, they had less inflammation in different parts of their bodies - inflammation being a hallmark of aging - and maintained a healthier gut. While more research is needed on exactly why HMW-HA has such beneficial effects, the researchers believe it is due to HMW-HA's ability to directly regulate the immune system.