The key to a long life might be having two mothers and no father, at least for mice. A team of researchers has found that the rodents live nearly 30% longer when they are genetically engineered to carry genes from two females but no males.

The finding may be a step toward understanding why the females of many mammalian species outlive their male counterparts.

Mice genetically derived from two mothers are smaller and live 30% longer than normally bred mice.  (Photo: ScienceNow/Tomohiro Kono )

Mice genetically derived from two mothers are smaller and live 30% longer than normally bred mice. (Photo: ScienceNow/Tomohiro Kono )

Developmental biologists Manabu Kawahara of Saga University in Saga, Japan, and Tomohiro Kono of the Tokyo University of Agriculture developed a technique to produce what they call bi-maternal mice.

They take an egg from a just-born mouse and manipulate the genes so that they behave as though they come from sperm.

Then they transplant that genetic material into unfertilized eggs taken from mature mice and implant the embryos into surrogate mothers. The result is healthy pups with two mothers and no father.

To study the effect on longevity, the researchers created 13 bi-maternal mice and an equal number of control mice through natural mating. All mice lived out their lives in identical sterile environments.

The bi-maternal mice were noticeably smaller and about two-thirds the weight of the normally bred animals. And, as the pair reports online this week in Human Reproduction, the bi-maternal mice lived an average of 842 days, 186 days longer than the controls. “I am really surprised,” says Kono.

“I initially thought they would only live as long as normal mice.”

Kono says the differences in body size and longevity do not result from genetic differences because all the mice were genetically very closely related.

Rather, Kono points to epigenetics, chemical modifications of genes that can affect how they function.

Epigenetic factors associated with the sperm genome could account for the differences in body size and longevity, he says.

Kono and Kawahara have identified one gene associated with postnatal growth that is less active in the bi-maternal mice than it is in the controls, for example, though Kono says many genes are likely to be involved.

The authors say their results are consistent with theories that male mammals have evolved larger body sizes to increase the chances of mating, though at the cost of a shorter life span; whereas females maximize their reproductive success by conserving energy for delivering and nurturing offspring.

“The experiment is simple, and the results are clear, and the difference in longevity is just amazing,” says Hiroyuki Sasaki, a geneticist and molecular biologist at Japan’s National Institute of Genetics in Mishima.

“What’s really significant is that this shows the importance of epigenetics.” — ScienceNow