Scientists have long noted that the naked mole rat (Heterocephalus glaber) defies many biological expectations: remarkable longevity and a surprising level of resilience. In a recent step, researchers explored the role of hyaluronan synthase 2, a gene linked to longevity, by inserting it into mice. The result was encouraging: altered cellular receptors, extended lifespans, and improved health markers. The team now plans further study to understand whether this unique creature may truly reveal a secret of immortality, or at least a pathway to prolonged youth.
The naked mole rat, sometimes called the hairless mole rat, displays striking resistance to age-related diseases. It shows unusual resilience to cancer, can endure extreme conditions without oxygen for extended periods, and shares social structures seen in some insect species. Despite its small size, it can live for decades, with lifespans up to 41 years on record—roughly ten times longer than similarly sized rodents. Most notably, it appears not to age in a conventional sense and maintains reproductive capacity across its life. It is as if time barely moves for this remarkable mammal.
The gene transfer experiment to mice was conducted by researchers at the University of Rochester in the United States and was reported in a high-profile scientific journal. The researchers describe the work as a proof of principle that longevity mechanisms from long-lived mammalian species can be transferred to enable extended healthspan in other animals, potentially informing future human aging research.
“Our study demonstrates a viable longevity mechanism,” notes Vera Gorbunova, a leading professor of biology and medicine at Rochester, who has long studied aging processes in mammals. “The findings show that longevity pathways evolved in the naked mole rat could, with careful adaptation, be useful for extending lifespan in other species.”
cancer resistance
Researchers concluded that the key to cancer resistance and extended lifespan lies in high molecular mass hyaluronic acid. To test this, they created transgenic mice that carry the naked mole rat version of the gene responsible for producing high molecular mass hyaluronic acid. The results showed elevated hyaluronan levels in multiple tissues and a lower rate of spontaneous and induced cancers, accompanied by longer life and better overall health. On average, life expectancy appeared to rise by about 4.4% in these engineered mice.
Additional benefits were observed: in mice with the gene inserted, inflammation declined across several tissues, and gut barrier function improved with aging. The researchers emphasize an immunomodulatory effect on immune cells and enhanced resistance to oxidative stress, alongside better gut health in aging animals.
As the mice aged, inflammation diminished in various parts of the body, and gut health remained sturdier than in controls. The team suggests that this longevity mechanism, honed in a hairless subterranean mammal, could be adapted to other species and might offer a route to improving human health and lifespan via high molecular mass hyaluronic acid.
fountain of youth for people?
Investigators from Rochester noted that naked mole rats contain roughly ten times more high molecular mass hyaluronic acid in their bodies than mice or humans. Hyaluronan, a polysaccharide responsible for skin tone, texture, and moisture, is also linked to the remarkable resistance to certain cancers in this species. When high molecular mass hyaluronic acid was removed from naked mole rat cells, tumors tended to arise more readily, suggesting a protective role. The aim has been to determine whether the positive effects observed in these animals can be translated to other species. The answer appears supportive.
One researcher summarized the timeline: it took about a decade from the initial discovery of high molecular density hyaluronic acid in naked mole rats to demonstrating that it improves health in mice. The next goal cited was translating this benefit to humans, with the plan to slow the degradation of hyaluronic acid or to boost its synthesis. Teams are already identifying molecules that reduce hyaluronan breakdown and testing them in preclinical settings.
Experts emphasize that these findings may offer a first example of how long-lived adaptations from a perennial species could be adapted to support human longevity and health. While promising, researchers caution that translation to humans will require thorough testing and careful consideration of safety and ethics.
exceptional longevity
Naked mole rats are mouse-sized rodents with exceptional longevity. They can live up to 41 years, roughly ten times longer than rodents of similar size. Unlike many other species, these mammals tend to avoid common age-related diseases such as neurodegeneration, cardiovascular disease, arthritis, or cancer as they age. There is, however, at least one recorded cancer case among individuals in captivity, attributed to living in oxygen-rich environments that differ from their natural underground habitat.
Scientists believe the species’ energy-sparing metabolism contributes to its extended healthspan. They speculate that slower aging, less predation pressure, and a distinct physiological state help explain why aging appears delayed in this animal. A crucial discovery from Ottawa-based researchers demonstrated that the mole rat can endure hypoxic conditions by lowering its metabolic rate by as much as 85% in certain circumstances, and it can survive extended periods without oxygen.
This line of research holds medical significance because hypoxia is linked to conditions such as stroke and chronic lung disorders. The work represents a foundational step toward novel treatments that could improve health outcomes in humans. In addition to oxygen deprivation tolerance, another study suggested that naked mole rats rewire glucose metabolism in youth, favoring alternate energy pathways that resemble plant-like metabolic strategies. Their colonies also organize in a cooperative, queen-led structure reminiscent of eusocial insects.
Reference work: Nature 2023 findings on hyaluronan pathways and longevity in mammals. [Citation: Nature, 2023 study on high molecular mass hyaluronic acid and aging in mammals.]
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