Mice live longer and show fewer signs of ageing when given a gene from naked mole rats which drives the production of hyaluronic acid.
Contrary to their wrinkly appearances, naked mole rats are masters of anti-ageing. They can live more than 40 years – more than six times as long . They also evade neurodegeneration, cardiovascular disease and cancer.
at the University of Rochester in New York and her colleagues previously found that the rodents’ secret to longevity is long chains of molecules of high-molecular-weight hyaluronic acid (HMW-HA). Hyaluronic acid is a lubricant surrounding tissues and cells in all animals, and because of its ability to retain water and hydrate skin, it is sometimes used in anti-ageing skin products. At high molecular weights, the substance exhibits anti-inflammatory properties.
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To see if its anti-ageing effects extend to other animals, Gorbunova and her colleagues inserted a gene from naked mole rats into the genomes of 84 mice before they were born, genetically modifying them to produce more HMW-HA. Then they compared the lifespans of the modified mice with those of 91 mice lacking the gene, and examined both groups’ organs for tumours after death. Mice with the gene lived 4.4 per cent longer on average than those without it. The modification also reduced how many mice died from cancer – 57 per cent compared with 70 per cent of the mice lacking the gene.
The team assessed signs of ageing in 13 unmodified mice and 14 modified mice at 24 months old. They measured 31 parameters such as body weight, hearing loss and forelimb strength, with higher scores indicating greater age-related declines in function. On average, the unmodified mice scored about twice as high as mice with the mole rat gene, suggesting increased HMW-HA production delays signs of ageing. The findings were presented at a symposium hosted by the New York Academy of Sciences on 10 May in New York City.
“We didn’t know if there was a lot of other stuff going on in [naked mole rats] that makes them resistant to cancer and live longer, but [this study] shows it is the high-molecular-weight hyaluronic acid in and of itself,” says at the University of Calgary in Canada.
HMW-HA may protect against disease and ageing in part by reducing proteins associated with inflammation, according to genetic analysis of tissue samples from the modified mice.
When the researchers screened the heart, kidneys, muscles and intestines for HMW-HA, they found higher amounts of the substance in modified mice, but not to the same degree as in naked mole rats. The researchers suggest this is because naked mole rats degrade their HMW-HA more slowly. This could explain why the mice didn’t see greater increases in lifespan or protection from cancer.
More research is needed to figure out exactly how HMW-HA works, which will then help us develop drugs or treatments mimicking these effects in humans, says Kuipers.
“You can’t put a naked mole rat gene into a human, right? So, the step from mice to humans, that’s going to take some other avenues,” she says.
bioRxiv
