How germline regulation, sex differences impact the lifespan of male, female vertebrates

“Germline cells” are responsible for passing genetic information from one generation to the next through the production of eggs and sperm in animals or pollen and ovules in plants. Classical evolutionary theories have long proposed tradeoffs among reproduction, damage repair, and lifespan, but exactly how the germline shapes vertebrate aging has remained unexplained.  

A new study by researchers at the Hebrew University of Jerusalem (HU) has revealed unexpected and sex-specific effects of germline regulation on longevity and the repair of tissues in animals with spinal cords (vertebrates). 

Contrary to classical evolutionary theories, it turns out that changing how the germline responsible for reproduction works can have different effects on males and females. This challenges conventional beliefs that reproduction and longevity are linked by a limited pool of resources. The research, the authors said, opens up new possibilities for understanding how our bodies age and the role of reproduction in that process. The findings open new avenues for understanding the complex interplay between reproduction, damage repair, and lifespan, offering fresh insights into the mechanisms governing aging in vertebrates.

It was conducted by Prof. Itamar Harel and a team of researchers at HU’s Alexander Silberman Institute of Life Science, who have just published the study in the prestigious journal Nature Aging under the title “The “The germline regulates longevity and somatic repair in a sex-specific manner.” 

Study introduces a paradigm shift

Harel’s research focused on the turquoise killifish (Nothobranchius furzeri), introducing a paradigm-shifting perspective. The team genetically halted germline differentiation at separate stages in turquoise killifish and meticulously examined the impact of different infertility “flavors” on their life-history. A comprehensive single-cell gonadal atlas was constructed, providing cell-type-specific markers crucial for downstream phenotypic analysis. Gonads are glands that produce hormones that are involved in reproduction and other functions in humans and animals.

The research conducted by HU doctoral students Eitan Moses and Tehila Atlan shows that removing the germline in vertebrates has different effects on males and females. It notably extends the lifespan of males and provides remarkable stress resistance in females. The main discoveries from the study indicate that only depleting the germline significantly improves the ability of females to repair the damage, while stopping germline differentiation doesn’t produce the same result. Interestingly, males without a germline showed a notable increase in lifespan, challenging the commonly held belief that the germline is always good for prolonging longevity.

Analyzing the genes and pathways, the study discovered that there are more of those connected to longer life than initially believed. Surprisingly, when they studied a tiny worm called Caenorhabditis elegans known for genetic and aging research, they found that these mechanisms related to living longer still worked.

The research also uncovered that germline depletion extended the amount of time that the males remained healthy through rejuvenated metabolic functions, suggesting a potential avenue for interventions to promote healthy aging in males.

The results suggest that different germline manipulation paradigms can yield pronounced sexually dimorphic phenotypes, introducing alternative mechanisms to classical evolutionary tradeoffs. Sexual dimorphism involves traits that are exaggerated or more developed in one of the sexes. The evolutionary basis of such phenotypes –including their development, appearance, and behavior – has usually been associated with fitness and resource availability.

Harel concluded that their study “opens new avenues for understanding the intricate balance between reproduction, damage repair, and lifespan” and that the “sex-specific nature of germline regulation challenges existing paradigms and paves the way for further exploration of alternative mechanisms governing aging in vertebrates.”