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.