The enduring mystery of why women outlive men may come down to the smallest and 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 gender differences in lifespan, and that removing the cells results in animals with the same life expectancy.
The experiments were conducted on small, turquoise killer fish, a freshwater species that reaches sexual maturity in two weeks and lives for a matter of months, but the researchers suspect that a similar biological mechanism may affect the lifespan gap in humans and other species as well.
“The aging process in killer fish is similar to that in humans, so I don’t think humans are necessarily more complicated,” said Prof Tohru Ishitani, the senior author of the study at Osaka University. “I think this research will be a stepping stone to understanding the control of aging in humans.”
Worldwide, women live on average about 5% longer than men. A multitude of factors contribute to the disparity, with young men more likely to die in accidents and by suicide, and women often leading healthier lifestyles. But the difference is also seen in other species: female monkeys and old world monkeys tend to live longer than their male counterparts.
For humans, the size of the life expectancy gap varies greatly between countries. 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, partly because of heavier drinking and smoking.
Ishitani said having sperm or eggs is one of the most obvious differences between males and females, so it makes sense to investigate whether or not it had an impact on lifespan. In a series of experiments, his team showed that eliminating the production of germ cells, which develop into sperm or eggs, led to longer-lived males and to females that died younger than usual, essentially closing the lifespan gap.
“We expected germ cell removal to extend the lifespan of both males and females, but it only lengthens male lifespan and shortens female lifespan,” Ishitani said. “It was unexpected, but we realized that this discovery could shed light on gender differences in lifespan.”
Write 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 estrogen increased the risk of cardiovascular disease. The males generated more vitamin D in their livers, which may explain their better bone, muscle and skin health.
The team went on to test whether supplying killer whale vitamin D extended lifespan and recorded increases of 21% in males and 7% in females. Although no adverse effects were seen, Ishitani said it was important to use the “appropriate amount”. In the UK, health officials recommend a daily 10 micrograms or 400 IU vitamin D supplement in autumn and winter. Take 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 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 rule out.
Dr David Clancy, who researches ways to extend a healthy lifespan at Lancaster University, said in studies of other animals, blocking reproduction increases lifespan, particularly in females, which is a trade-off between growth and reproduction versus maintenance and life expectancy.
“Here, removal of sperm or egg progenitor cells shortened lifespan in females, but in males it was extended, as was growth, probably through a mechanism related to increased vitamin D activity,” he said. “It is clear that the signaling that these cells do that modulates lifespan differs between the sexes in these fish, and most likely in other animals as well.”
