Mice produced in the laboratory from two biological mothers and without a father have been found to live significantly longer than normal mice bred from a mother and a father. These findings indicate that genetic traits inherited from the father but not the mother may play an important role in ageing and longevity.
Researchers from Saga University and Tokyo University of Agriculture, Japan, took DNA from eggs of one day-old mice and genetically modified it so that it would behave like sperm. They then used it to fertilise eggs from adult mice, thereby producing offspring with two mothers, dubbed bi-maternal mice. Control mice were bred that were genetically identical to the bi-maternal mice except that they had been conceived conventionally using genetic material from a sperm and an egg.
Professor Tomohiro Kono, who led the study, explained the researchers' goals: 'We have known for some time that women tend to live longer than men in almost all countries worldwide, and that these sex-related differences in longevity also occur in many other mammalian species... The study may give an answer to the fundamental questions: that is, whether longevity in mammals is controlled by the [genes] of only one or both parents, and just maybe, why women are at an advantage over men with regard to the lifespan.'
Reporting in the journal Human Reproduction, the researchers compared the lifespans of 13 bi-maternal mice with those of 13 control mice. On average, the bi-maternal mice lived for 841.5 days - 186 days longer than the control mice, which averaged 655.5 days. The researchers also found that the bi-maternal mice were significantly smaller and lighter than the control mice. There were also signs that the bi-maternal mice had better immune systems than the control mice, as they had higher numbers of eosinophils (a type of white blood cell that play an important role in protecting mammals against parasites and infections) in their blood.
The researchers believe that the effects they observed may result from a genetic process called 'imprinting' whereby the activity of a gene depends on whether it is inherited from the mother or the father. They suggest that a gene called Rasgrf1, found on chromosome 9, may be responsible for the increased lifespan and smaller weight of the bi-maternal mice.
Rasgrf1 is an imprinted gene that is always turned on when it is inherited from the father and always turned off when it is inherited from the mother. The bi-maternal mice had two inactive Rasgrf1 genes as they were both inherited from female mice instead of having the usual one active Rasgrf1 gene inherited from a father and one inactive Rasgrf1 gene inherited from a mother. However, Professor Kono emphasised: 'it's not clear whether Rasgrf1 is definitively associated with mouse longevity, but it is one of the strong candidates... we cannot eliminate the possibility that other, unknown genes that rely on their paternal inheritance to function normally may be responsible.'
Professor Kay-Tee Khaw, an expert in ageing at Cambridge University, commented to the BBC: 'These are interesting findings but I think any sex differences in longevity - which in humans have changed over time and differ in different environments - may have more complex explanations than any single gene'.