Photo/Illutration Turquoise killifish that have been engineered to lack reproductive cells, bottom row, grow larger than those with reproductive cells, both in females, left column, and males, right column. (Provided by Osaka University)

While females of many animal species, including humans, live longer on average than their male counterparts, the reason remained a mystery—but a group of scientists from Osaka University may have cracked the code.

It all comes down to reproductive cells.

The researchers reported in a U.S. science journal that males of a particular fish species have longer life spans when engineered to have no sperm, while females have shorter life spans when doctored to have no eggs.

Previous studies have found that nematodes and flies hatched not to have reproductive cells have extended life spans. However, the relationship between reproductive cells and longevity in vertebrate animals remained unclear.

Since it is difficult to conduct experiments on animals with long life spans, the scientists studied the turquoise killifish. These fish inhabit arid regions of Africa, are about 4 centimeters long and only live a few months.

Female turquoise killifish normally live about 20 percent longer than males do.

The scholars used genetic manipulation to produce male and female turquoise killifish without reproductive cells. Both grew to larger sizes than usual for that species.

However, in terms of longevity, the removal of reproductive cells had the opposite effect on the male and female fish: In males, the average life span increased by 13 percent, but it dropped by 7 percent in females.

Why did the lack of reproductive cells impact their bodies this way?

The researchers found that the female fish without eggs produced less of the hormone estrogen. The lower estrogen levels caused blood to clot more easily and increased rates of cardiovascular diseases.

The male fish without sperm, on the other hand, exhibited less deterioration related to aging. These fish showed less decrease in bone and muscle volume and less skin deterioration over time.

To investigate how the aging process was suppressed, the scientists scrutinized genes that work in different organs of the fish’s body and found an increase in genes related to the functions of vitamin D.

Vitamin D, which is not only ingested from food but is also synthesized in the body, plays a key role in the maintenance of health by acting on muscles, skin and immune cells.

The researchers administered vitamin D to adult turquoise killifish to determine if the substance effectively lengthened their life spans.

They found that vitamin D increased the average life span of turquoise killifish by 21 percent in males and 7 percent in females.

“We are the first to show that vitamin D functions as an anti-aging hormone,” said Tohru Ishitani, a professor with the Osaka University Research Institute for Microbial Diseases and one of the group members.

The exact relationship between sperm and vitamin D is not yet understood and remains a subject of future studies, Ishitani added.

The research results were published on June 13 in Science Advances, a U.S. science journal (https://www.science.org/doi/10.1126/sciadv.adi1621).

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