Germ cells drive sex-specific lifespan differences, revealing role of vitamin D in extending lifespan: study

Women live longer than men. This is not unique to humans, but is a trend seen in many other animals as well. Biologists theorize that the difference in life expectancy between the sexes may be partly to do with reproduction, but how?

In published studies, Scientific progress, Researchers at Osaka University have discovered for the first time that germ cells, which develop into eggs in females and sperm in males, drive sex-specific differences in lifespan in vertebrates.

The researchers studied aging in turquoise killifish, a small, fast-growing freshwater fish that only lives for a few months. Like humans, female killifish live longer than males. But when the researchers removed reproductive cells from these fish, they found that males and females had roughly the same lifespan.

“After removing the germ cells, male medaka lived longer than normal, while females’ lifespans were shortened,” explains lead author Kota Abe. “We wanted to understand why germ cells have such different effects on males and females. Our next step was to investigate the factors that cause this.”

The team found that hormone signaling differs significantly between females and males. Female killifish, which lack germ cells, have significantly less estrogen signaling, which can increase the risk of cardiovascular disease and shorten lifespan. Females also have significantly more growth factor signaling (insulin-like growth factor 1), which allows them to grow larger but also suppresses internal signals that are important for maintaining health and slowing aging.

In contrast, male killifish, which lack germ cells, had improved muscle, skin and bone health. Interestingly, these fish had increased amounts of a substance that activates vitamin D, and there was also evidence of vitamin D signaling in muscles and skin.

“Vitamin D, which can be thought of as a hormone, is best known for keeping bones strong and healthy, but it also appears to have broader positive effects throughout the body. The team’s results suggest that vitamin D may extend lifespan, which prompted them to test whether vitamin D supplements could extend lifespan in fish.”

“When we administered active vitamin D, we found that lifespan was significantly extended in both men and women, suggesting that vitamin D signaling confers health benefits throughout the body,” explains senior author Toru Ishitani.

“Our study suggests that vitamin D signaling may influence lifespan in other vertebrates, including humans.”

The discovery that germ cells have opposing effects on male and female lifespan provides an important clue to unraveling the mysterious interplay between reproduction, aging and lifespan. Exactly how vitamin D fits into this puzzle is unclear, but it may be part of a future strategy to extend healthy lifespan.