University of Rochester scientists have successfully transmitted a longevity gene from naked mole rats to mice, resulting in better health and an extension of the mouse’s lifespan.
Naked mole rats have long captivated the scientific community due to their long lifespans and outstanding resistance to age-related diseases. The Rochester investigators have opened up great possibilities for unlocking the secrets of aging and extending the human lifespan by introducing a specific gene responsible for enhanced cellular repair and protection into mice.
“Our study provides a proof of principle that unique longevity mechanisms that evolved in long-lived mammalian species can be exported to improve the lifespans of other mammals,” notes Vera Gorbunova, the Doris Johns Cherry Professor of Biology and Medicine at Rochester. Gorbunova, along with Andrei Seluanov, a Professor of Biology.
In the research published in Nature, the investigators and their coworkers reported that they successfully transferred a gene responsible for producing high molecular weight hyaluronic acid (HMW-HA) from a naked mole rat to mice. This resulted in better health and a 4.4% increase in the mice’s median lifespan.
A Unique Mechanism For Cancer Resistance
Naked mole rats are mouse-sized rodents with remarkable longevity for their size; they can live up to 41 years, nearly ten times longer than comparable-sized rodents. Naked mole rats, unlike many other species, do not frequently develop diseases such as neurodegeneration, cardiovascular disease, arthritis, and cancer as they age.
Gorbunova and Seluanov have spent decades studying the distinct mechanisms that naked mole rats use to safeguard themselves from aging and disease.
The researchers previously found that HMW-HA is one of the mechanisms underlying naked mole rats’ unusual cancer resistance. Naked mole rats have approximately ten times more HMW-HA in their bodies than mice or humans. The cells were more likely to form tumors when the investigators eliminated HMW-HA from naked mole rat cells.
Gorbunova, Seluanov, and their coworkers wanted to see if the positive effects of HMW-HA could be replicated in other animals.
Transferring a Gene That Produces HMW-HA
The researchers genetically altered a mouse model to produce the naked mole rat version of the hyaluronan synthase 2 gene, which is responsible for producing the protein HMW-HA. The naked mole rat version of the hyaluronan synthase 2 gene appears to be improved to drive greater gene expression.
The naked mole rat version of the gene was found to provide better protection against both spontaneous and chemically induced skin cancer in mice. In addition, the mice had better overall health and lived longer than regular mice. The naked mole rat version of the gene mice aged with less inflammation in different parts of their bodies (inflammation is a hallmark of aging) and a healthier gut.
While more research is needed to determine why HMW-HA has such positive effects, the researchers believe it is because of the ability of HMW-HA to directly regulate the immune system.
A Fountain of Youth For Humans?
The findings open new avenues for investigating how HMW-HA could be used to improve human longevity and lessen inflammation-related diseases.
It took us 10 years from the discovery of HMW-HA in the naked mole rat to showing that HMW-HA improves health in mice. Our next goal is to transfer this benefit to humans.”
Vera Gorbunova, the Doris Johns Cherry Professor, Biology and Medicine, University of Rochester
They believe they can achieve this through one of two methods: slowing down HMW-HA degradation or increasing HMW-HA synthesis.
“We already have identified molecules that slow down hyaluronan degradation and are testing them in pre-clinical trials. We hope that our findings will provide the first, but not the last, example of how longevity adaptations from a long-lived species can be adapted to benefit human longevity and health.”
Andrei Seluanov, Department of Biology, University of Rochester
Zhang, Z., et al. (2023) Increased hyaluronan by naked mole-rat Has2 improves healthspan in mice. Nature. doi.org/10.1038/s41586-023-06463-0.