Eliminating Germ Cells Removes the Sex Difference in Life Span from Killifish

There are a great many hypotheses as to why there is a difference in life expectancy between sexes in many species, and even more when it comes to humans. Since the difference exists in other species, it seems reasonable to throw out most of the thinking that involves behavioral differences or lifestyle choice differences in humans: arguments that men are more prone to risky behavior, less conscientious in use of medical resources, and so forth. From an evolutionary perspective, one can model how reproductive strategies might affect the process of natural selection and its interaction with pace of aging, but even if the models turn out to be correct - and they are usually much debated - that doesn't say much about the specific biochemistry involved in determining life span differences between sexes.

Today's open access research materials present a compelling argument for germline cells to orchestrate processes that lengthen female life span and shorten male life span. Removing the germline acts to shorten female life span and extend male life span in the short-lived killifish species. This dovetails nicely with the existing evolutionary perspectives, and at least narrows down the area of study for those who want to chase down specific mechanisms. The challenge in this arena is rarely in identifying a mechanism that may contribute to the end result of interest, it is to prove that this mechanism is important relative to all of the others that may or may not be involved. Fortunately, modern genetic technologies make it possible, albeit still expensive when conducted in volume, to knock out cell functions one by one. Researchers might progress from here to ever more specific acts of sabotage in germline cell biochemistry, in search of the mechanisms that affect life span.

The gender gap in life expectancy: are eggs and sperm partly responsible?

Women live longer than men. This isn't unique to humans, either; we see this trend in a wide range of other animals. Biologists have theorized that the discrepancy in life expectancy between sexes might be partly related to reproduction, but how? Researchers have discovered for the first time that germ cells, the cells that develop into eggs in females and sperm in males, drive sex-dependent lifespan differences in vertebrate animals.

The researchers examined aging in the turquoise killifish, a small, fast-growing freshwater fish with a lifespan of only a few months. As in humans, female killifish live longer than males. However, when the researchers removed the germ cells from these fish, they found that males and females had similar lifespans. The team found that hormonal signaling was very different in females than in males. Female killifish without germ cells had significantly less estrogen signaling, which can shorten lifespan by increasing cardiovascular disease risk. The females also had significantly more growth factor signaling (insulin-like growth factor 1). This made the females grow larger while also suppressing signals within the body important for maintaining health and slowing aging. In contrast, male killifish without germ cells had improved muscle, skin, and bone health. Interestingly, these fish had increased amounts of a substance that activates vitamin D, as well as evidence of vitamin D signaling in their muscles and skin.

Sex-dependent regulation of vertebrate somatic growth and aging by germ cells

The function of germ cells in somatic growth and aging has been demonstrated in invertebrate models but remains unclear in vertebrates. We demonstrated sex-dependent somatic regulation by germ cells in the short-lived vertebrate model Nothobranchius furzeri. In females, germ cell removal shortened life span, decreased estrogen, and increased insulin-like growth factor 1 (IGF-1) signaling. In contrast, germ cell removal in males improved their health with increased vitamin D signaling. Body size increased in both sexes but was caused by different signaling pathways, i.e., IGF-1 and vitamin D in females and males, respectively. Thus, vertebrate germ cells regulate somatic growth and aging through different pathways of the endocrine system, depending on the sex, which may underlie the sexual difference in reproductive strategies.


Please include me in the conversation. Thanks Michael

Posted by: Michael Slattery at June 19th, 2024 1:08 PM
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