The enduring mystery of why women outlive men may come down to the smallest and the largest cells in the body: the sperm and eggs that are central to human reproduction.
Scientists in Japan have shown for the first time in vertebrates that cells that develop into eggs in females and sperm in males drive sex differences in lifespan, and that removing the cells leads to animals with the same life expectancy.
The experiments were performed on small, turquoise killifish, a freshwater species that reaches sexual maturity in a fortnight and lives for a matter of months, but the researchers suspect a similar biological mechanism could influence the lifespan gap in humans and other species too.
“The ageing process in killifish is similar to that in humans, so I don’t think humans are necessarily more complicated,” Prof Tohru Ishitani, the senior author on the study at Osaka University, said. “I think this research will be a stepping stone to understanding the control of ageing in humans.”
Globally, on average, women live about 5% longer than men. A multitude of factors contribute to the disparity, with young men more likely to die in accidents and through suicide, and women often leading healthier lifestyles. But the disparity is seen in other species, too: female apes and old world monkeys tend to live longer than their male counterparts.
For humans, the size of the life expectancy gap varies widely between countries. The life expectancy for people born in the UK between 2020 and 2022 is 78.6 years for men and 82.6 years for women. In Russia, meanwhile, men tend to die about 13 years earlier than women, in part because of heavier drinking and smoking.
Ishitani said having sperm or eggs was one of the most obvious differences between males and females, so it made sense to investigate whether or not they had an impact on lifespan. In a series of experiments, his team showed that knocking out the production of germ cells, which develop into sperm or eggs, led to longer-living males and to females that died younger than usual, essentially closing the lifespan gap.
“We expected that germ cell removal would extend the lifespan of both males and females, but it extends only male lifespan and shortens female lifespan,” Ishitani said. “It was unexpected, but we realised that this discovery may shed light on sex differences in lifespan.”
Writing in Science Advances, the researchers describe how blocking sperm and egg production had knock-on effects for the fish. Hormonal changes in the females spurred growth at the expense of maintaining healthy tissues, while reduced oestrogen raised the risk of cardiovascular disease. The males generated more vitamin D in their livers, potentially explaining their better bone, muscle and skin health.
The team went on to test whether giving killifish vitamin D extended lifespan and recorded increases of 21% in males and 7% in females. While no ill effects were seen, Ishitani said it was important to use the “appropriate amount”. In the UK, health officials recommend a daily 10 microgram or 400 IU vitamin D supplement in the autumn and winter. Taking more than 100 micrograms, or 4000 IU, daily can be harmful.
Whether sperm suppresses men’s life expectancy is unclear, but Ishitani said there is some evidence to support the idea. A 2012 study of 81 Korean eunuchs found that they lived 14 to 19 years longer than non-castrated men from a similar socioeconomic background. But the records date from the 16th to the 19th century and other factors are hard to exclude.
Dr David Clancy, who researches ways to extend healthy lifespan at the University of Lancaster, said in studies of other animals, blocking reproductivity increases lifespan, especially in females, suggesting a trade-off between growth and reproduction versus maintenance and lifespan.
“Here, removing sperm or egg precursor cells saw lifespan of females shortened, but in males it was extended, as was growth, likely by a mechanism related to increased vitamin D activity,” he said. “Clearly, the signalling these cells do which modulates lifespan differs between the sexes in these fish, and quite probably in other animals too.”
