A mole rat gene inserted into mice extended lifespan and improved health, findings that may point to new ways of supporting healthier ageing.
The gene increased production of a large form of hyaluronan, a naturally occurring gel-like substance between cells that helps tissue repair and cell-to-cell communication.
Mice carrying the naked mole rat version of the gene showed an approximately 4.4 per cent increase in median lifespan, alongside multiple markers of healthier ageing.
Naked mole rats have become a focus of ageing research because they combine an exceptional lifespan with unusual resistance to many age-linked diseases, including cancer.
Researchers at the University of Rochester traced part of that resilience to hyaluronan.
The molecule’s effects depend on its size: large forms are often linked to anti-inflammatory and tissue-protective behaviour, while smaller fragments can act as danger signals that increase inflammation.
Vera Gorbunova, professor of biology and medicine at the University of Rochester in the US, said: “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.”
The engineered mice were better protected against both spontaneous tumours and chemically induced skin cancer.
They also showed reduced inflammation across tissues, a notable finding because persistent low-grade inflammation, sometimes called inflammaging, is widely seen as one of the central drivers of age-related decline.
The research also linked the large form of hyaluronan to age-related gut health. As animals age, the gut barrier can become leakier, allowing inflammatory triggers to pass into the bloodstream.
The engineered mice showed protection against this deterioration.
Follow-up work found abundant high-molecular-mass hyaluronan across multiple species of subterranean mammals, often absent in closely related above-ground species, suggesting it may be part of a broader evolutionary toolkit for surviving long lives under harsh conditions.
The team said gene transfer is not the end goal. Gorbunova said: “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.”
Two practical routes are being pursued: increasing production of the large form of hyaluronan, or slowing its breakdown.
Andrei Seluanov, who co-leads the research, said: “We already have identified molecules that slow down hyaluronan degradation and are testing them in pre-clinical trials.”
One candidate identified through screening is delphinidin, a plant pigment found in various fruits and vegetables.
In tests, it was found to increase levels of the large form of hyaluronan in cells and mouse tissues, reduce migration and invasion in multiple cancer cell lines, and suppress melanoma metastasis in mice.
However, the researchers acknowledged the approach has limits. A later study found that mice expressing the naked mole rat gene showed improvements in several late-life health measures but did not show protection from age-related hearing loss, suggesting some organs may be less reachable by this pathway than others.
The Rochester team said turning these findings into human therapies will likely depend on precision: maintaining the right molecular form of hyaluronan, targeting the right balance of production versus breakdown, and monitoring carefully for trade-offs as different tissues respond in different ways.
