How naked mole-rats defy aging and cancer

HostIf you saw one of these things in the wild, you might think you were looking at a tiny, pink, wrinkled cocktail sausage with teeth. It's the naked mole-rat, and let’s be honest, it looks like it's having a really rough time. But while a common house mouse is already hitting its golden years at age three, these guys are still going strong when they're thirty. How does something that looks like it's already falling apart actually live ten times longer than its cousins?

GuestIt's because they break a rule that almost every other mammal has to follow. There's a mathematical law called the Gompertz-Makeham law, which is basically the math of dying. It says the older you get, the more likely you're to die. For humans, that risk of death doubles roughly every eight years. It's like a clock that ticks faster and faster as the years go by. But for naked mole-rats, that clock doesn't seem to exist. Their risk of dying at age thirty is essentially the same as it was when they were one. Scientists call this negligible senescence. It's a fancy way of saying they don't really show signs of getting old. They do eventually die from things like infections or predators, but they show almost no decline in their heart function, their bone density, or how their bodies handle energy over several decades. They just don't experience the slow breakdown we think of as a normal part of life.

HostThat sounds like they're basically immortal. If nothing eats them and they don't get an infection, do they just live forever?

GuestNot forever, but they're certainly pushing the limits. One of the main reasons they stay so healthy is that they're famously resistant to cancer. For decades, researchers couldn't find a single case of a tumor in the species. The secret is a substance called High Molecular Weight Hyaluronan, or H M W H A. It's a type of sugar found in the space between cells in all mammals, but the version in a naked mole-rat is five times larger than ours. It's very thick and very gooey. This thick sugar acts like a biological sensor. When cells begin to crowd together, which is the very first step in forming a tumor, this long sugar triggers a process called early contact inhibition. It sends a signal to the cells to stop dividing immediately. It basically chokes off any potential cancer before it can ever gain a foothold.

HostBut if you're filled with this thick, heavy goo, how do you even move around? It seems like it would make the animal incredibly stiff or keep its body from growing when it actually needs to.

GuestIt actually makes them very stretchy. That sugar is part of why their skin is so loose and wrinkled, which lets them squeeze through tight tunnels underground without getting hurt. But staying healthy is about more than just avoiding tumors. It's about keeping the inside of the cell clean. Most aging is caused by biological garbage piling up. Our cells build proteins all day long, and as we get older, the machines that build those proteins, called ribosomes, start making more mistakes. You get these bent, broken proteins that gunk up the system and lead to diseases like Alzheimer’s. Naked mole-rats have evolved extremely high-fidelity ribosomes. Their machines are just better at their jobs and make way fewer errors. They also have a highly efficient proteasome system, which acts like a cellular recycling plant. It identifies and breaks down damaged proteins with much more speed and precision than human cells can.

HostI can see how that works for a rodent, but we're a lot more complex than a mole-rat. I have a hard time seeing how a few less protein mistakes would stop us from getting old.

GuestWell, those small mistakes are exactly what causes the body to fail over time. The most exciting thing is that we have already proven this can be moved from one species to another. In a major study, researchers took the gene that makes that thick mole-rat sugar and put it into mice. Those mice didn't just live longer; they had way fewer cases of cancer and much lower levels of whole-body inflammation. This means we might not have to treat every individual disease of old age one by one. Instead, we could look at drug treatments that mimic that thick sugar or make our protein building more stable. We're looking at the possibility of keeping our cells healthy across our entire lifespan by copying what these animals do naturally.

HostThat little pink rodent with the big teeth might be the key to making sure we all stay as strong and healthy at eighty as we're today.