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Naked Mole Rats Offer Clues to Living Longer

These creatures live more than five times longer than would be expected for their size. Research into the biological mechanisms underlying their longevity could suggest ideas for slowing aging in people



Courtesy Publishers Weekly

Editor's note: This article is adapted from the book The Youth Pill: Scientists at the Brink of an Anti-Aging Revolution, by David Stipp. We are presenting it in conjunction with Stipp's article "A New Path to Longevity" in the January 2012 issue of Scientific American. Additional information can be found in "What Unusually Long-Lived Animals Say about Human Aging."

The study of aging tends to raise the kind of deceptively simple questions children ask, such as, “Why did Spot, who was the same age as me, get old and die before I grew up?” Such queries quickly lead to deep mysteries, none of which are more riveting than those surrounding extraordinarily long-lived species.

One that has come to the fore in recent years is a grotesque, mouse-sized rodent called the naked mole-rat. Resembling saber-toothed sausages, they’re even weirder than they look. For one thing, they live in termite-like, underground colonies populated by workers that serve as a support system for a single breeding queen. But their most mind-bending trait is an incredibly slow rate of aging. In captivity they can reach about 30 years of age, ten times the typical life spans of their mouse cousins. To see how remarkable that is, imagine a species of primates with a life span of a thousand years.

The leading authority on mole-rat longevity is Rochelle Buffenstein, a researcher who maintains a sizable colony of the animals at the Barshop Institute for Longevity and Aging Studies, part of the University of Texas Health Science Center at San Antonio. When I visited her one afternoon, she led me to a dimly lit room where I found myself surrounded by scores of chirping mole-rats merrily tending their nests inside clusters of shoebox-sized containers connected by clear plastic tubes. To my surprise there was no airtight barrier protecting them from the outer world's germs. Mole-rats are so hardy, she explained, that there’s no need for that. Underscoring the point, she suddenly picked one up and handed it to me. It was “the old man of the colony,” she said—her most senior mole-rat.

Up close he turned out to be oddly endearing, possessed of the bald, wrinkled, buck-toothed, querulous, squinty-eyed look of a slightly demented codger born well before the age of orthodontia. His exact age wasn't known—he’d been caught in the wild—but Buffenstein estimated he was pushing 29. It suddenly dawned on me that he might be the oldest rodent on the planet. I gingerly handed him back, feeling as if I’d been momentarily entrusted with a 2,000-year-old Han Dynasty vase.

The life style of the naked mole-rat Natives of East Africa, mole-rats were introduced to science in 1842 by Eduard Rüppell, a German naturalist known for heroically traipsing the biosphere and bringing pieces of it home. Despite their curious appearance, the rodents, officially named Heterocephalus glaber (meaning, roughly, weird-headed baldy), didn’t get much attention until Jennifer Jarvis, a Kenya-reared daughter of English missionaries, discovered in 1981 that they’re an extremely rare, mammalian version of social insects like termites. Each mole-rat colony is dominated by a large-bodied queen that mates with one to three consorts and produces hundreds of babies during her life. Intriguingly, the queens appear to keep workers in line by literally pushing them around, and when a royal mole-rat encounters a groundling in a tunnel she shoves it backward or walks over it. Such aggression appears to help suppress the lower orders’ fertility, as well as cue their subservient behavior—rarely-shoved workers in tunnels remote from the queen's chamber reportedly tend to goof off.

A native of Zimbabwe, Buffenstein got hooked on mole-rats in the early 1980s while studying under Jarvis at the University of Cape Town in South Africa. Among other things, she was taught how to capture the elusive rodents in the wild. "We'd scrape the soil down” to make a breach in their tunnels, she explained, “and then sit there with a hoe. When a worker came to investigate the breach, we'd bring the hoe down behind it," preventing its retreat so as to grab it. "Once I stuck my hand in a tunnel and came across a dead snake. I nearly died. There's nothing more frightening than putting your hand in the ground and feeling something cold and slimy."

The mole-rats Buffenstein captured in the early 1980s proved to be wonderfully durable lab animals, and as time passed they gradually took over her career. By mid-2001, her oldest one was making history every day—approaching his 28th birthday, he’d outlived the previous holder of the rodent longevity record, an Asian porcupine that had lived for 27 years and 4 months. His official designation was mole-rat number 007, and so of course she nicknamed him James Bond.

Fittingly, he was a sexy bon vivant—as senior consort of his queen, he continued siring pups right up to his death in April 2002 at age 28.3. As is often the case with mole-rats, it wasn’t clear what finally did him in; a post-mortem showed no signs of cancer or other diseases that typically kill rodents. (Indeed, mole-rats appear to be immune to cancer, a common cause of death in other lab rodents.)

Longevity clues emerge
Galvanized by 007’s outlandish longevity, Buffenstein specialized in the study of mole-rat aging. Or rather, non-aging: In 2002, she reported that the animals show no age-related changes in bone mineral density, body mass, body-fat content, or other signs of physical deterioration during their first two decades. Obviously they aren’t immortal, but you wouldn’t know it to look at them during their first 20 years of life.

More surprises followed when she began investigating how they do it. For instance, she discovered that they blatantly defy the free radical theory of aging, which holds that damage caused by free radicals, highly reactive molecules produced in cells as by-products of energy metabolism, underlies aging. Buffenstein showed that mole-rats’ lipids, proteins and DNA, the basic constituents of cells, exhibit two to eight times more free radical damage than the same molecules in mice—the animals are like badly rusted winter-beaters that miraculously keep chugging along year after year.

Probing deeper, she and colleagues have found a number of mole-rat peculiarities that may contribute to their longevity. For instance, both mole-rats and long-lived bats have remarkably low insulin levels in their blood (insulin regulates blood sugar). That fits with data on long-lived, calorie-restricted rodents, which also have very low insulin levels. And among men participating in the Baltimore Longitudinal Study of Aging, ongoing since 1958, those with lower blood insulin levels have tended to live longer.

Other research by Buffenstein and colleagues at the Barshop Institute suggests that the rodents’ cells contain special “chaperone” proteins that help keep various other key proteins in good working order. More recently, she participated in the sequencing of the naked mole-rat genome, which has revealed a number of genes possibly related to their extreme longevity—their resistance to cancer, for example, may stem in part from gene variants that slow cell proliferation.

At this point, the secret of their great durability is just beginning to come into focus. But research on the animals, and on other extraordinarily long-lived species such as bats, has already expanded gerontologists’ minds about aging in ways that studies on short-lived lab animals like mice couldn’t. Indeed, when it comes to aging, as with all else in the living world, evolution has generated "endless forms most beautiful and most wonderful," as Darwin so nicely put it. Not least among the strange beauties is a little buck-toothed burrower that ages like a demigod.

Adapted from The Youth Pill: Scientists at the Brink of an Anti-Aging Revolution, by David Stipp (www.davidstipp.com).

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