Genes that are passed on by fathers may be shortening the lifespans of their offspring, research has suggested.
Scientists have discovered that mice with two biological mothers but no father live about 30 per cent longer than usual, in an experiment that could have implications for understanding human ageing.
The findings, from a Japanese team, raise the possibility that genes transmitted by sperm may increase the offspring’s growth at the expense of a longer lifespan.
While it is not yet known whether the effect also applies to humans, the research promises new insights into genetic influences on the ageing process in mammals that might eventually be exploited to slow it down.
It could also illuminate the way that genes provided by mothers and fathers combine in the embryo, improving understanding of reproduction and certain diseases.
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Professor Tomohiro Kono, of the Tokyo University of Agriculture, who led the research, said that it could even offer clues to why women typically live longer than men. He said: “The study may give an answer to the fundamental questions: that is, whether longevity in mammals is controlled by the genome composition of only one or both parents and, just maybe, why women are at an advantage over men with regard to the lifespan.”
The new findings about ageing have emerged as the spin-off of a biological trick developed by the same team, which led in 2004 to the birth of a mouse called Kaguya with no biological father. Kaguya, named after a character from a Japanese fairytale, was the first mammal to be conceived by two biological mothers and no father, after Professor Kono devised a way of genetically manipulating mouse eggs to make them behave like sperm.
Before her birth, scientists had thought this was impossible in mammals, because of a phenomenon known as genetic imprinting that requires embryos to inherit both male and female DNA.
Imprinted genes are switched on or off depending on whether they are inherited from the sperm or the egg, and both are generally necessary for development. Without certain paternally imprinted genes, for example, the embryos of mammals normally die because they do not form a placenta.
Kaguya lived for 793 days, compared with an average lifespan for her strain of mouse of between 600 and 700 days, leading Professor Kono to wonder whether her unique conception had contributed to her longevity.
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His team thus created another 13 “bimaternal” (BM) mice, conceived from two eggs, and compared these with 13 female mice of the same strain produced in the normal fashion and raised in the same environment.
In a paper published today in the journal Human Reproduction , the scientists report that the BM mice lived on average for 186 days longer than the normal animals.
The increase was equivalent to a group of British women living to an average age of 105, compared with the current average of 81. BM mice are always female, as were the animals in the control group.
The longer-lived BM mice were significantly smaller and lighter than the normal ones. Professor Kono said that the increased lifespans of the BM mice probably reflected the abnormal way in which their genomes were imprinted, because they had no DNA of male origin. This suggests that certain imprinted genes from the father’s sperm may suppress lifespan, perhaps while also increasing body size.
The effect may be explained by the different reproductive interests of males and females. As males do not have to nourish foetuses and infants, they gain an advantage by passing on genes that encourage maximum growth as early as possible. Females have an interest in limiting that growth to protect their own health.
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Other research has established that a calorie-restricted diet can prolong the lifespan of animals, including mice. Professor Robin Lovell-Badge, of the National Institute for Medical Research in London, said: “Almost certainly it is an imprinting ‘problem’, either with the gene they talk about or perhaps other genes involved in insulin-like growth factor activity, which play a role in longevity.”