Naked mole rats and the anti-oxidant myth

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Photo by Benimoto. Creative Commons Attribution 2.0 Generic license.

If the more than $3 billion of antioxidant supplements sold each year is any indication, you probably have bottles of vitamins C, E, A, and selenium pills sitting on a shelf somewhere, and I wouldn't put it past you to have stashed away some grape seeds and pomegranate extracts while chomping on your blueberry chewing gum. Antioxidant-rich products like these are the most tried and true youth preservatives, according to those who sell them. The vendors can cite decades of supporting research on the free radical theory of aging, which suggests that ubiquitous molecular fiends known as oxygen free radicals constantly threaten to rust out our cells. The theory's bottom line is that our best hope to counter creeping body rot is to pop lots of radical-neutralizing antioxidants.

It's a tribute to the power of advertising that so many people still buy this by the billions of dollars. Truth be told, in recent years it has been discredited by a thick sheaf of studies, from shocking clinical results with antioxidant vitamins to flabbergasting findings about a bizarre little rodent called the naked mole-rat. And it's now quite clear that the antioxidant myth may be hazardous to your health.

This isn't to say the free radical theory of aging is all wrong. Highly reactive free radicals are indeed churned out by our cells' power plants, mitochondria. And just as the theory says, the rogue molecules constantly blow holes in DNA, proteins and other pieces of our inner infrastructure, necessitating endless repairs. There's also good evidence that the damage doesn't always get repaired, potentially contributing to cancer, heart disease, neurodegeneration–and just about every other baddie coming at us in later life.

Further, there's no question that we need modest amounts of antioxidant vitamins to survive. As scurvy lads everywhere can attest, ingesting less than about 10 milligrams of vitamin C a day, for instance, induces extreme fatigue, bleeding gums, swollen limbs, and ultimately heart failure.

But here are the rubs: Feeding antioxidants to animals has never yielded convincing evidence of slowed aging, despite scores of studies over the past 50 years aimed at proving antioxidants have fountain-of-youth potential. Curiouser still, a host of clinical studies in recent years have shown that heavy doses of antioxidant vitamins E and A, and beta-carotene (that orange stuff in carrots, a precursor of vitamin A) actually increase the overall risk of death in people by about 5%.

How could this be?

Well, strange to say, scientists have known since the 1970s that free radicals serve as chemical messengers within cells as well as agents of destruction–among other things, they help regulate blood pressure and signal immune cells to attack invading microbes. And when levels of free radicals within cells rise–which is thought to happen, for instance, when we exercise hard–the radicals themselves act as signals to boost our cells' natural antioxidant defenses. Thus, raining megadoses of antioxidants down on our cells may damp down their raise-the-deflector-shields message, causing them to fail to fully erect their strongest defenses against radical damage–ones designed and honed by evolution over a couple billion years–leaving us open to damage that's not compensated for by the ingested antioxidants that discombulated the system.

You might think the answer is simply to design antioxidant supplements that mimic our super-duper natural ones. This has been tried, and it has shown some limited promise in animal studies. But fans of this idea have had to contend with another rub in recent years: The weird imperviousness of the naked mole-rat (NMR) to body rot.

Burrowing, mouse-sized rodents with fearsome incisors, NMRs have been aptly described as saber-toothed sausages by Rochelle Buffenstein, a leading authority on the animals. NMRs' first claim to famous strangeness was the discovery that they're a mammalian version of the social insects, such as honeybees, and their underground colonies in East Africa are populated by workers that act as a support system for a single breeding queen. In recent years, another NMR peculiarity has come to the fore–their extreme longevity. They're known to live up to about 30 years, some ten times longer than mice–and in fact longer than any other rodent.

A couple of years ago I visited Buffenstein's NMR colony at the Barshop Institute for Longevity and Aging Studies outside San Antonio. Walking into a dimly lit room, I found myself surrounded by scores of chirping NMRs merrily tending their nests inside clusters of shoebox-sized containers connected by clear plastic tubes. While I stood there marveling, Buffenstein suddenly plucked one out of its colony and handed it to me.

Up close it had the bald, wrinkled, buck-toothed, querulous, squinty-eyed look of a slightly demented codger born well before the age of orthodontia. In fact, it was truly ancient — Buffenstein told me that the animal, the "old man" of her colonies, was pushing twenty-nine. It suddenly dawned on me that this was probably the oldest rodent on the planet, and just maybe the longest-lived one ever. I gingerly handed it back to her feeling as if I had been momentarily entrusted with a two-thousand-year-old Han Dynasty vase.

Seeking NMRs' longevity secret, Buffenstein discovered in 2002 that the animals basically show no metabolic signs of aging, such as changes in body-fat content or bone density, during their first two decades — they may not be immortal, but you wouldn't know it from looking at them until they finally keel over around 30 for reasons yet to be explained.

Here's the real shocker, though: They have remarkably lax natural antioxidant defenses, and Buffenstein has shown that their tissues are positively riddled with free-radical damage — far more than the damage found in the tissues of much-shorter-lived mice. You might say NMRs are like badly rusted winter beaters somehow continuing to chug along year and year, dragging the increasingly battered free radical theory of aging behind them like a falling-off muffler.

Buffenstein has begun to get a handle on how they resist the ravages of time. (You can read all about that in my new book.) Exactly how they cope with their heavy inner rust, though, remains an enigma wrapped in a riddle hidden in a fanged hot dog. But whenever I pass the antioxidant pills in the drug store these days, I picture a happy-go-lucky, rust-colored Rufus, Walt Disney's NMR character — and keep right on walking.

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