The magical animals in nature are endless treasures for humans to find cures and improve the quality of life. Among them, the naked mole rat is undoubtedly a shining star. This rodent, with its wrinkled pink skin and iconic buck teeth, may look ugly, but it hides unique clues to fighting off aging and cancer.
Naked mole rats are surprisingly long-lived stars. They can live for more than 30 years - although far less than humans, but you should know that other rodents of similar size only live a few years. For example, the mice we are familiar with only live for a few years at most. Can live 6 years. Another miraculous quality of naked mole rats is that they are virtually free of cancer and do not show symptoms of dementia, cardiovascular disease and other diseases associated with aging.
With their enviable "ageless" characteristics, naked mole rats have naturally attracted the attention of scientists. In 2013, this little animal appeared on the cover of Nature magazine. In this far-reaching paper, the team of professors Andrei Seluanov and Vera Gorbunova of the University of Rochester proposed that high molecular weight hyaluronic acid (HMM-HA) is the key to almost insulating naked mole rats from cancer. They secrete large amounts of hyaluronic acid, a sticky substance that inhibits rapid cell division and prevents cells from becoming cancerous. It is also a potential way for naked mole rats to live longer. This paper also found that once hyaluronic acid is removed or the naked mole rat hyaluronic acid synthase 2 gene (nmrHas2), which regulates its synthesis, is knocked down, the special ability of naked mole rats to inhibit cancer growth becomes weaker.
Since then, different research teams have further explored and discussed the anti-cancer and anti-aging mechanisms of naked mole rats, for example, revealing their unique DNA repair mechanism. But an unresolved question is whether these magical abilities can be transplanted to other animals, and even ultimately help humans live longer and healthier lives?
Ten years later, the paper published under the leadership of Professors Seluanov and Gorbunova was once again published in Nature magazine. This time, based on their research 10 years ago, the research team successfully moved the "longevity gene" nmrHas2 of the naked mole rat into mice, improving the health of the mice and extending their lifespan. This proof-of-concept study shows that the naked mole rat's longevity mechanism could also bring benefits to other relatively short-lived animals.
In the latest research, the author's goal is to enable mice to express large amounts of hyaluronic acid, the secret to the longevity of naked mole rats, and then observe whether the effects of hyaluronic acid can be reproduced in mice. In fact, hyaluronic acid synthase 2 (HAS2) and Has2 genes are universally possessed by mammals, but the naked mole rat’s version of the Has2 gene seems to drive stronger HAS2 synthesis while making the naked mole rat’s HAS2 specific on individual amino acids. There are differences, which may be why they can synthesize hyaluronic acid in large quantities.
In order to achieve the above goals, the research team constructed transgenic mice overexpressing nmrHas2. These mice begin to express nmrHas2 at 3 months of age. Subsequently, the authors conducted long-term observation and analysis of these transgenic mice and control mice.
As a result, increased hyaluronic acid levels were observed in multiple tissues of the transgenic mice. These mice had fewer spontaneous and chemically induced tumors, and their rate of death from cancer (57%) was significantly lower than that of the control group (70%). In older mice over 27 months old, the difference was even more pronounced: only 49% of the transgenic mice developed cancer, compared with 83% of the control mice.
In addition, the lifespan of these transgenic mice was also extended: compared with the control group, their median lifespan and maximum lifespan were extended by 4.4% and 12.2%, respectively, and their health conditions were also improved.
Transcriptome analysis also showed that the transcriptomes of transgenic mice were closer to those of long-lived species. The most significant change is that these nmrHas2 mice have less inflammation in different tissues in the body, and inflammation can induce a variety of aging-related diseases. Hyaluronic acid can reduce inflammation through a variety of different pathways, including direct immune regulation of immune cells, avoiding oxidative stress damage, and enhancing intestinal barrier function during aging.
Taken together, this study confirms that the longevity mechanism of the naked mole rat can be transferred to other species, thus opening up new possibilities for using hyaluronic acid to extend lifespan and improve health.
The ultimate goal of the research team is naturally to use the findings from naked mole rats to help humans achieve health and longevity. Professors Seluanov and Gorbunova spent ten years from discovering the role of hyaluronic acid to using it to improve the health of mice. It is not difficult to imagine that the road for this mechanism to be used by humans will be long, but the future it outlines is worth waiting for more discoveries in the next decade with hope.