Genetics and stem cells

'Eve-olution' – natural selection may help women live longer

“Revealed, at last: why women live longer than men” reports The Independent. It says that “a mutation in the power producers of the body's cells is more harmful to males than females”.

This news is based on research on the DNA in the “powerhouses” of cells - the mitochondria - in fruit flies, and their influence on aging and lifespan.

Most of our genes come in pairs. We receive one of the pair from our mother, and the corresponding gene from our father.

But mitochondrial DNA is different in that only females pass on their mitochondria to their offspring.

This is thought to be responsible for an effect that has been termed as the ‘Mother’s Curse’ by geneticists.

The ‘curse’ is that mutations in mitochondrial DNA that are harmful to females will be filtered out by the process of natural selection. Women with beneficial mutations are more likely to survive and reproduce than women with harmful mutations.

But men are essentially an evolutionary ‘dead end’ for mitochondrial DNA. There is no evolutionary pressure filtering out mutations that are harmful to males, while at same time, promoting ‘useful male’ mutations.

The researchers found some evidence from fruit flies to support the theory of the ‘Mother’s Curse’. Variations in mitochondrial DNA were linked with aging and lifespan in male fruit flies, but not female fruit flies.

Aging is a complex process, and it is likely that many factors are involved. More research will be needed to determine whether these findings in fruit flies also apply to other species, including humans.

Even if the findings do apply to humans, there appears little that current medicine can do to compensate for the ‘Mother’s Curse’.

Where did the story come from?

This research was conducted by scientists from Monash University, Australia, and Lancaster University, UK. The study was funded by the Australian Research Council.

The study was published in the peer-reviewed scientific journal: Current Biology.

The media give variable representations of this research. The BBC makes it clear that this is research in fruit flies, but the Independent article applies the research to humans and mentions flies only in the final sentence of its lengthy article.

What kind of research was this?

This scientific research centres upon the transmission from mother to offspring of genetic material in mitochondria, and how this may affect the two sexes differently. Mitochondria are the “powerhouses” of the cells, providing them with energy. Mitochondria are also thought to play a role in aging in the cell as they produce free radicals which can damage the cell, believed to be one part of aging.

The mitochondria carry their own circular piece of DNA, separate from the rest of the DNA in the cells. It carries the blueprint for making proteins that are needed in energy making processes. Only mothers pass on their mitochondrial DNA to their offspring (both male and female), as the man’s sperm does not contribute any mitochondria when it fertilises the egg. The current study investigates the theory that women’s mitochondrial DNA could accumulate mutations which are beneficial to her, or do her little or no harm, but are detrimental in a male, including mutations that contribute to making men age faster than women. As males do not pass on mitochondria to their offspring, it would not be possible for mutations that are detrimental to males to be gradually filtered out through natural selection.

What did the research involve?

The researchers used fruit flies for their experiments. They took 13 strains of fruit fly which had different mitochondrial DNA, but the rest of their DNA was the same. They then assessed whether males and females of these strains aged differently and how long they lived. The flies were kept in identical conditions, so that any differences seen would be due to their mitochondrial differences alone.

They determined the sequence of “letters” (nucleotides) in the parts of the mitochondrial DNA that carry instructions for making protein in all 13 strains of fruit fly. They then looked at whether the single letter variations in mitochondrial DNA were related to the sex-differences in aging across the strains.

What were the basic results?

The researchers found that males aged more quickly and did not live as long as females in all 13 strains. They found that the single letter variations in mitochondrial DNA were significantly related to aging and longevity in male flies but not female flies. They also found that the more differences there were in the mitochondrial DNA between any two strains, the more differences there were between the males and females in these strains in terms of their aging and longevity. These findings suggested that these mitochondrial variations were affecting aging and longevity in males but not females. They also suggested that several mutations were each having a small effect on aging and longevity, rather than a small number of mutations having a large effect.

How did the researchers interpret the results?

The researchers concluded that they had shown that mitochondrial DNA contains variations that affect male aging specifically and not females. They say these findings show the “dramatic and hitherto unappreciated consequences of maternal inheritance of [mitochondrial] DNA to male life history evolution”. They say that their findings suggest that genetic variance in mitochondria might be a significant contributor to the differences in lifespan and ageing seen between males and females across the animal kingdom.

Conclusion

The findings of this study in fruit flies support the theory that DNA in the mitochondria can accumulate changes which specifically influence ageing in males but not females, and that this may contribute to the differences in ageing and lifespan between the sexes. This is possible because although both males and females have mitochondria, only the females pass these on to their offspring. Changes to the mitochondrial DNA which are sufficiently harmful to the female to make her less likely to reproduce would be less likely to be passed on to offspring. Changes to the mitochondrial DNA that are harmful to males, but have little or no effect on females would not affect her ability to pass on her mitochondria, and therefore would be passed on to her male and female offspring, having a detrimental effect on the males.

This research supports the mitochondria as a possible contributor to the difference in lifespan between male and female fruit flies, and the researchers suggest it may also occur in other species. More research will be needed to determine whether this is the case. Ageing is a complex process, and the differences between men and women may be influenced by a variety of factors, of which mitochondria may only be one.

Even if the findings do apply to humans, there appears little that current medicine can do to compensate for any potentially harmful mutations in male mitochondria DNA.


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