Naked mole rats (Heterocephalus glaber) are not pretty rodents; their yellow teeth and pale, wrinkly skin make them look like a hairless gopher that has sat in a bath far too long. But while they don't look beautiful, they age gracefully. They survive past 30 years old, whereas laboratory mice rarely have a third birthday. And unlike mice and humans, age doesn't curse naked mole rats with cancer, dementia or heart disease. So, what's the secret to their longevity? Scientists previously found a few factors that keep them young: their DNA repairs itself well when damaged and their cells have loads of antioxidants. But their most interesting anti-aging strategy may be outside their cells altogether. Most cells live in a blanket of molecules and minerals called an ‘extracellular matrix’. In naked mole rats, this blanket is woven from a thicker fabric: naked mole rats produce a heavier and larger version of the molecule hyaluronan, which is the backbone of this extracellular matrix. As Andrei Seluanov and Vera Gorbunova's team at the University of Rochester, USA, show, this extra padding protects cells from inflammation and early death.
To better understand this anti-aging strategy, Seluanov and Gorbunova's team genetically modified mice to produce this naked mole rat version of hyaluronan throughout their skin, muscles and internal organs. Then, the researchers recorded how long they lived, and whether they developed cancer with age – as older mice tend to do.
The naked mole rat gene was a powerful anti-aging treatment. Mice lived up to 12% longer lives with this bulkier hyaluronan molecule. If these results were translated directly to humans, that would mean an extra precious decade of life. The mice also developed less cancer, even when exposed to tumour-producing chemicals.
The scientists then asked, as the mice are living longer, does that mean they live stronger? They gave the mice an array of tests to measure their ‘frailty index’ – a measure of health and vitality. These tests include things like hearing and vision tests, coat condition, body temperature and weight. Mice with the naked mole rat molecule showed a lower frailty index, meaning they were healthier and more robust. They had denser bones, produced a stronger grip and were more capable in coordination tests. As the team put it, the mice not only had a longer lifespan but also had ‘an improved health span’.
Next, the researchers asked exactly how this naked mole rat molecule kept mice alive and thriving. First, they looked in the genes for clues, and genetic scans showed that inflammation genes were dialled down throughout multiple organs. This was a good lead as inflammation is a risk factor for age-related diseases such as cancer, arthritis and heart disease. To double-check, they took blood samples to look for signs of inflammation; there were fewer pro-inflammatory molecules in the blood of mice with heavy hyaluronan. Finally, they did a third test, by injecting a bacterial protein that causes inflammation and checking how the mice reacted. There was less inflammation in their tissues, and fewer pro-inflammatory chemicals in their blood. This may be naked mole rats’ secret of youth: this thick hyaluronan coating may protect cells from inflammation, so they live longer and avoid disease.
Perhaps the most interesting thing about this anti-aging chemical is, it's already in each of us. Humans produce heavy hyaluronan too, we just don't make much. For centuries, humans have dreamt of anti-aging elixirs and the mystical Fountain of Youth. Instead, the Fountain of Youth may be embodied in the heavy hyaluronan of naked mole rats – nearly blind rodents, with lots of wrinkles and yellowed teeth.
