Age Before Beauty

When the famed German naturalist Eduard Rüppell first laid eyes on a naked mole rat, he thought that a terrible illness must have attacked the creature to make it so impossibly ugly. The rodents, which he first described in 1842, are almost totally bald and wrinkled-pink, with tusk-like front teeth framed by long whiskers. Only after pulling several more naked mole rats from their maze-like burrows in the warm red dirt of the Horn of Africa did he realize that, for Heterocephalus glaber, homely was healthy.

Scientists didn’t guess just how healthy, however, until the 1980s, when researchers began gathering naked mole rat specimens in order to study their unusual social behaviors. Naked mole rats are one of only two mammal species (the other is the Damaraland mole rat) that live in colonies in which a single “queen” produces offspring, while others work collectively to tunnel, find food, clean, and care for the young. Back then, “when we collected the animals, we had no idea how long they would live,” says Rochelle Buffenstein, a professor of physiology at the Barshop Institute for Longevity and Aging Studies at the University of Texas. But as years, then decades ticked by without appearing to affect the naked mole rat specimens, Buffenstein and colleagues began to think that the bizarre-looking rodents might be able to provide insights that could improve human health.

It turns out that naked mole rats are, in fact, the longest-lived rodents in the world. Body size is a good predictor of maximum lifespans in animals -- typically, the bigger the body, the longer the animal survives. But though naked mole rats are the same size as mice, they can live up to 10 times as long, making it to age 30 and beyond in remarkably robust fashion. Buffenstein and others have discovered that naked mole rats don’t start to show signs of aging -- such as diminished activity levels, reduced cardiac strength, loss of muscle and bone, and decreasing numbers of neurons representing mental function -- until they’re well into old-age, the equivalent of 90-plus in human years. In a recent study in the journal Aging Cell, she and colleagues report that throughout their lives, naked mole rats retain high levels of a brain protein called neuregulin-1 that helps protect neurons from damage but typically becomes less concentrated in us as we age -- a potential contributing cause of dementia and Alzheimer’s disease.

Understanding how naked mole rats hold onto their neuregulin could help us fight cognitive decline. What’s more, the skin and upper respiratory tract of naked mole rats seems to be immune to pain or irritation from ammonia, chili pepper, acidic substances like lemon juice, and inflammation. If scientists could replicate that feat in humans, they might virtually eliminate chronic joint and muscle pain, including arthritis. Most exciting of all, Buffenstein says, is the discovery that naked mole rats are “very resistant to many forms of cancer.” While 70 percent of mice die from the disease, it has yet to be spotted in a single naked mole rat.

Living underground -- which naked mole rat ancestors have been doing since the Miocene epoch -- is most likely how the rodents evolved such biological advantages. “It’s like they’re from a different planet,” says Thomas Park, a biologist at the University of Illinois at Chicago who studies the animals. The only time naked mole rats come near the surface -- and fleetingly encounter fresh air -- is when they kick dirt out of their tunnels, which can go eight feet deep and span more than a mile, and which include designated chambers for nesting and toileting. (The waste room is also where naked mole rats dispose of their dead). Their brief contact with the mix of gasses we breathe seems to have given them an unusual tolerance for exposure to high levels of oxygen -- which causes the “oxidative stress,” or cell damage, that scientists currently believe leads to the eventual breakdown of our bodies.

Deeper underground, however, their tunnels -- which can house between 100 and 300 naked mole rats -- are low on oxygen and high on carbon dioxide. So their inhabitants have also adapted to protect themselves from a degree of oxygen deprivation that would render a person brain-dead in a matter of minutes. Their blood is more efficient at capturing oxygen, and their metabolism is slower than that of surface-dwelling rodents, partly because naked mole rats are the world’s only known cold-blooded mammal. Instead of needing to process food and expend energy to maintain a constant body temperature, mole rats regulate their internal thermostat by heading deeper underground to cool down and closer to the sunbaked surface to warm up.

Scientists aren’t sure how many naked mole rats exist in the wild, but the International Union for the Conservation of Nature does not consider them threatened, and so far, agriculture and development haven’t overtaken their arid East African grassland habitat. Meanwhile, scientists sequenced the naked mole rat’s genome last year and are moving fast to translate mole-rat wellness strategies into treatments for humans.

“The first time somebody sees one of these animals, they go, ‘Eww, gross.’ But they grow on you,” Park says. They can be “quite gentle and cute.” Could following their biological example help us ward of illness and age more gracefully? Buffenstein says the notion is “not as far-fetched as it sounds” -- or, in the case of the naked mole rat, as it looks.

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