2 December 2009

Why women live longer than men

by Kate Melville

The difference in male and female longevity may be originating at the genome level, say Japanese researchers who suggest that the sperm genome has a detrimental effect on longevity in mammals. Their study, published in the journal Human Reproduction, found that female mice produced by using genetic material from two mothers but no father live significantly longer than mice with the normal mix of maternal and paternal genes. Their findings provide the first direct evidence that sperm genes may have a detrimental effect on lifespan.

The average lifespan for the type of mice used in the study is between 600-700 days. The mice created from two female genomes (bi-maternal (BM) mice) lived an average of 186 days longer than control mice created from the normal combination of a male and female genome.

"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. However, the reason for this difference was unclear and, in particular, it was not known whether longevity in mammals was controlled by the genome composition of only one or both parents," explained study co-author Professor Tomohiro Kono, from the Department of Bioscience, Tokyo University of Agriculture.

To conduct the study, Dr. Kono and colleague Dr Manabu Kawahara collected non-growing oocytes (eggs) from day-old mice, manipulated the genetic material in these eggs so that the genes behaved like sperm genes, and then transplanted this manipulated genetic material into the fully grown, unfertilized oocytes of adult mice that had their nuclei removed. These reconstructed oocytes developed into embryos, which were transferred into surrogate mother mice. The mice that were born as a result were bi-maternal, having genetic material from two mothers, but no father. The control mice were created through natural mating.

The longest time that any of the control mice lived was 996 days, with all but one of them dying by 800 days, while the longest time alive for the BM mice was 1045 days, with all but three of them living for more than 800 days. The researchers checked the weight of the mice at 49 days and 600 days and found that the BM mice were significantly lighter and smaller than the control mice. The BM mice also seemed to have better immune systems, with a significant increase in one type of white blood cell (eosinophil).

"We believe that the most likely reason for the differences in longevity relates to the repression of a gene called Rasgrf1 in the BM mice. This gene normally expresses from the paternally inherited chromosome and is an imprinted gene on chromosome 9 associated with post-natal growth. Thus far, it's not clear whether Rasgrf1 is definitively associated with mouse longevity, but it is one of the strong candidates," said Dr. Kono.

The results are consistent with sex-specific reproductive strategies, for example; male individuals maximizing fitness by an intense investment in reproduction by way of a larger body size in order to achieve more breeding opportunities, resulting in shorter longevity. In contrast, female individuals usually do not engage in such costly behaviors and instead tend to optimize their reproductive output by conserving energy for delivery, providing for offspring, foraging and predator avoidance.

"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. Our results suggest sex differences in longevity originating at the genome level, implying that the sperm genome has a detrimental effect on longevity in mammals," concluded Dr. Kono.

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Source: European Society for Human Reproduction and Embryology