Eating a calorie-restricted diet and being female are the best bets for living longer, at least for animals. Now scientists have discovered that some links may exist between the two.

Women live about five years longer on average than men, and a similar longevity advantage exists for other mammal species, including rats. Numerous experiments have also shown that eating a nutritionally complete diet relatively low in calories can also extend lifespan: A daily calorie decrease of 30 percent correlates to living 30 to 50 percent longer than normal for all animal species tested thus far, including mice and dogs.

To find out whether these two scenarios for longer life share common molecular mechanisms, Adamo Valle of University of the Balearic Islands in Spain and his colleagues compared male and female rats. Each gender group was separated into two groups, one fed a normal diet and the other fed a calorie-restricted diet. Valle’s team then compared the activity levels of hundreds of proteins in the animals’ livers, which help to regulate energy metabolism.

Among these proteins, 11 had different activity levels in both cases — when comparing females with males and when comparing the groups on normal or calorie-restricted diets, the team reports online and in an upcoming Journal of Proteome Research. Valle and his colleagues say it makes sense that these 11 proteins might affect longevity since they play roles in energy metabolism, antioxidant mechanisms, stress response and cardiovascular protection. Most of these proteins had not been identified in previous studies of calorie restriction and longevity.

The differences in the calorie-restricted males mimicked the pattern seen in females on a normal diet, the scientists report.

It’s the first time that scientists have found similarities between the longevity effects of gender and calorie restriction, but some scientists say that common ground is understandable.

“It doesn’t surprise me at all,” comments Peter DiStefano, chief scientific officer for Elixir Pharmaceuticals, a biotech company in Cambridge, Mass., developing diabetes drugs based on calorie-restriction research. DiStefano speculates that estrogen might cause some of these effects through the hormone’s action on the hypothalamus, a region of the brain that controls many aspects of feeding behavior and energy metabolism.

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