No part of the body is truly isolated; all organs, systems, and cell populations interact with all of the others in various ways. Cells secrete and take up countless varieties of molecules and vesicles, carried throughout the body by the circulatory system to cause reactions elsewhere. Given the strong impact of reproductive success on the evolution of a species, including the characteristics of aging in that species, it perhaps shouldn’t be surprising to find that germline cells get an outsized vote in the behavior of other bodily systems. In some senses, the individuals of a species are just temporary vehicles that exist to ensure the continuation of the germline, and they are shaped by the requirements of that task.
Aging is a complex biological process whose regulatory mechanisms remain incompletely understood. Accumulating evidence indicates that germ cells play pivotal roles in the systemic regulation of aging. The link between germ cells and somatic aging was first established in invertebrate models, where germ cells positively regulate the rate of organismal aging. However, whether and how this relationship operates in vertebrates has remained unresolved for nearly a quarter of a century. Recently, using the short-lived vertebrate model Nothobranchius furzeri, we demonstrated that germ cells exert sex-dependent effects on somatic aging.
In males, germ cell ablation improved healthspan and extended lifespan, accompanied by enhanced vitamin D signaling. In contrast, germ cell removal in females shortened lifespan, associated with increased IGF-1 signaling and reduced estrogen signaling. These findings suggest a vertebrate-specific mechanistic link between germ cells and somatic tissues mediated by sex-specific endocrine signaling. Such a mechanism may contribute to sexual dimorphism in reproductive strategies and potentially underlie the female longevity advantage observed across many species.
