The successful transfer of a gene that produces a specific type of hyaluronic acid could pave the way for improving the health and lifespan of humans.
Researchers at the University of Rochester have successfully exported a longevity gene from naked mole rats to mice – a transfer that resulted in both improved health and an extension of the mouse’s lifespan [1].
Longevity.Technology: Naked mole rats, which are known for their long lifespans and exceptional resistance to age-related diseases, have been a focus of longevity research for some time. By introducing a specific gene responsible for improved cellular repair and protection into mice, the Rochester researchers have created promising opportunities to better understand the mechanisms behind aging and potentially increase human lifespan.
“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,” says Vera Gorbunova, the Doris Johns Cherry Professor of biology and medicine at Rochester [2].
Gorbunova, along with Andrei Seluanov, a professor of biology, and their colleagues, report in a study published in Nature that they successfully transferred a gene responsible for making high molecular weight hyaluronic acid (HMW-HA) from a naked mole rat to mice. This led to improved health and an approximate 4.4% increase in median lifespan for the mice.
A unique mechanism for cancer resistance
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 age-related diseases; in fact, they often manage to avoid developing neurodegenerative diseases, cardiovascular disease, arthritis and cancer as they age. Gorbunova and Seluanov spent years researching the unique mechanisms that naked mole rats use to protect themselves against aging and diseases.
The researchers previously discovered that high molecular weight hyaluronic acid is one mechanism responsible for naked mole rats’ unusual resistance to cancer. Compared with mice and humans, naked mole rats have about ten times more HMW-HA in their bodies, and when the researchers removed HMW-HA from naked mole rat cells, the cells were more likely to form tumors.
Gorbunova, Seluanov and their colleagues wanted to see if these positive effects of HMW-HA could also be reproduced in other animals – the first step towards a potential human longevity therapy.
Transferring a gene that produces high molecular weight hyaluronic acid
The Rochester 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 appears 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 with regular mice [1]. 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 to determine just why HMW-HA has such beneficial effects, the researchers believe HMW-HA’s ability to directly regulate the immune system is a key factor.
From rat to human?
The findings open the door to the possibility of HMW-HA being used to improve lifespan and reduce inflammation-related diseases in humans.
“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,” Gorbunova says. “Our next goal is to transfer this benefit to humans [2].”
The researchers have identified two potential routes of research – slowing down the degradation of HMW-HA and enhancing HMW-HA synthesis.
“We already have identified molecules that slow down hyaluronan degradation and are testing them in pre-clinical trials,” Seluanov says. “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 [2].”
[1] https://www.nature.com/articles/s41586-023-06463-0
[2] https://www.rochester.edu/newscenter/gene-transfer-hmw-ha-naked-mole-rats-extends-mice-lifespan-565032/
