A Longevity Diet That's Easy to Stomach

Slashing calories by one-third extends the lives of rodents, but adhering to the harsh diet would be difficult for people. Now researchers find that mice live longer when they ingest less of only one nutrient, suggesting that less-extreme measures also fend off mortality.

Long life would be nice--but not if the regimen that stalls your demise also makes you miserable. Unfortunately, the only method that's been proven to extend the lives of lab animals from fruit flies to mice involves cutting calories by 30% to 40%. Even if this so-called calorie restriction (CR) worked in people--an uncertain proposition--sticking to such an extreme diet wouldn't be very satisfying. But a new study suggests that more palatable ways to achieve the same goal might exist. Researchers have shown that mice live longer when their otherwise full meals contain small quantities of methionine, an amino acid found in every protein.

The study reveals that reducing intake of this one amino acid imparts at least some of the effects of CR, says evolutionary biologist Linda Partridge of University College London: "That suggests that it's not calories, it's the restriction of particular nutrients that is responsible for the full effect." Sorting out how CR and methionine limitation boost longevity could help researchers design a practical diet or develop a drug that would enhance human health.

For at least 70 years, researchers have known that CR extends the lives of mice and rats, lowers cancer risk, and improves metabolism (see "Counting Up the Calories, Holding Back the Years?"). Although it sounds like a miracle diet, CR comes with some serious side effects: Animals on a CR regimen have a lower body temperature and are less muscular, more susceptible to bacterial infection, and slower to heal wounds than their fully fed counterparts. As a result, scientists are interested in developing interventions that produce the benefits of CR without imparting side effects or requiring the will power to sustain such an extreme diet.

To start, researchers have tested a variety of diets, each lacking a single nutrient, to see whether a simpler regimen can mimic the effects of CR. In 1993, scientists discovered that a diet lean in methionine, an amino acid not produced by the body, delays death in rats. But no one knew whether other animals would respond similarly to the regime. To find out, pathologist Richard Miller of the University of Michigan, Ann Arbor, and colleagues served mice methionine-meager cuisine. They found that the oldest animals scampered 100 days longer than did those on normal feed--a longevity boost of almost 10%--suggesting that cutting back on methionine extends the lives of mice as well as rats.

The methionine-restricted mice also experienced some of CR's other health benefits. Animals on the test diet harbored smaller quantities of blood glucose after fasting, a sign of healthy metabolism. They also produced lower quantities of several hormones known to wane in CR animals.

"The most significant thing is that the hormone profile ... looks very much like [that of] a calorically restricted mouse," says gerontologist Steven Austad of the University of Texas Health Science Center (UTHSC) in San Antonio. That observation suggests that the methionine-free diet mimics important aspects of CR in addition to increasing longevity, although no one knows how much the effects of the two diets overlap.

The next step, say researchers, is to determine why avoiding methionine extends life span. One hypothesis is that the methionine-less diet could be inducing CR by causing animals to eat less: A lack of methionine might make food taste bad to mice, for instance. But that doesn't appear to be true. Mice in both groups ate about the same amount of food, says Miller. And the methionine-deprived mice were smaller than controls for most of their lives, which means that, gram for gram, they consumed more chow adjusted for their body weight. "If they eat the same but weigh less, where are those extra calories going?" asks physiologist Roger McCarter of Pennsylvania State University, University Park. The animals are probably absorbing less nutrients than normally fed animals do, says Miller. To answer the question definitively, researchers need to rigorously measure how much food animals take in, how much they excrete, and how active they are, says McCarter.

It's unlikely that CR animals live longer simply because they eat less methionine. Ample evidence indicates that CR works by restricting calorie intake--not by reducing the amounts of any particular nutrient, says gerontologist Edward Masoro, a professor emeritus at UTHSC now living in Charleston, South Carolina. However, the two diets could work in similar ways. Reducing methionine amounts and cutting calories might extend life by stressing animals mildly, thereby activating survival mechanisms, says Masoro. According to this theory, known as hormesis, stresses that aren't severe enough to permanently damage a cell or tissue spark the production of protective molecules that heighten an animal's capacity to survive over the long haul (see "Cruel to Be Kind").

Even if methionine deficiency can't account for all the effects of CR, it might feed into the way organisms assess their food supply. CR animals might sense deprivation by noting the absence of a few key components that normally reflect nutrient availability. Methionine might be a particularly robust indicator, says Partridge, because it's found in every protein. So monitoring methionine amounts would provide a good measure of whether protein intake is adequate.

Miller also entertains the possibility that methionine limitation and CR might toy with life span by different mechanisms. For instance, reducing methionine quantities might limit production of toxic methionine derivatives or boost quantities of the antioxidant glutathione. Miller finds that methionine-restricted animals are more resistant to oxidative stress than their methionine-saturated counterparts. The observation should give pause to folks who are currently taking methionine supplements. "The ironic thing is that lots of people are suggesting that people supplement their diets with methionine because it enhances antioxidant activity," says Austad. Miller's findings are "exactly the opposite" of what supplement pushers espouse, he says.

But even if reducing methionine consumption were the healthier choice, dieters would likely find it difficult to cut back: All natural proteins contain this amino acid, so people can't avoid it in a conventional diet and adherents would have to eat artificial--or at least highly processed--food. And as with CR, scientists don't know whether people would live longer on a low-methionine diet. But further studies on how these two diets extend life might reveal common secrets that could lead to relatively simple--and perhaps still delicious--ways for people to grow old and remain satisfied.

R. John Davenport is an associate editor of SAGE Crossroads' sister site, SAGE KE . He likes his tofu with methionine, thank you very much.