Males induce premature demise of the opposite sex by multifaceted strategies

Abstract

Interactions between the sexes negatively impact health in many species. In Caenorhabditis, males shorten the lifespan of the opposite sex—hermaphrodites or females. Here we use transcriptomic profiling and targeted screens to systematically uncover conserved genes involved in male-induced demise in C. elegans. Some genes (for example, delm-2, acbp-3), when knocked down, are specifically protective against male-induced demise. Others (for example, sri-40), when knocked down, extend lifespan with and without males, suggesting general mechanisms of protection. In contrast, many classical long-lived mutants are impacted more negatively than wild type by the presence of males, highlighting the importance of sexual environment for longevity. Interestingly, genes induced by males are triggered by specific male components (seminal fluid, sperm and pheromone), and manipulating these genes in combination in hermaphrodites induces stronger protection. One of these genes, the conserved ion channel delm-2, acts in the nervous system and intestine to regulate lipid metabolism. Our analysis reveals striking differences in longevity in single sex versus mixed sex environments and uncovers elaborate strategies elicited by sexual interactions that could extend to other species.

piRNAs regulate a Hedgehog germline-to-soma pro-aging signal

“…One of the most upregulated genes, sri-40 (Fig. 1h ), was also significantly induced in whole body after mating with males and, when reduced, extends lifespan with and without males, suggesting its involvement in general protection of mating-induced death 34 . Genes downregulated in the mated germline include metabolic processes (rRNA, cellular aromatic compound and heterocycle metabolic process) (Fig.…”

“…4a ). Since the pro-aging signal originates from the germline, it must be germline-specific; we subtracted those genes that are also upregulated in mated glp-1 germlineless worms 34 from the original list, reducing the number of candidates to 418 ( Source Data , Fig. 4a and Extended Data Fig.…”

“…1f) 12 . The longevity decrease after mating is mediated by multiple factors, including seminal fluid transfer, male sperm-induced germline hyperactivity, and male pheromone toxicity 12,13,[32][33][34] . While seminal fluid-mediated death involves insulin-like peptides and the insulin/FOXO signaling pathway, the germline-specific pro-aging signal that induces shrinking is unknown 12 .…”

“…Microarrays. Microarray data of mated and unmated glp-1(e2141) was retrieved from a previous publication 34 . Microarray data of mated and unmated fog-2(q71) was retrieved from a previous publication 61 .…”

AC. elegansmale pheromone feminizes germline gene expression in hermaphrodites and imposes life-history costs

“…Finally, interactions with males are detrimental to C. elegans hermaphrodites (Shi and Murphy 2014; Ting, et al 2014; Booth, et al 2022) and some of this effect is due to male-excreted compounds (Maures, et al 2014; Shi, et al 2017). Previously, we showed that ascr#10 shortens the hermaphrodite lifespan (Aprison and Ruvinsky 2016; Ludewig, et al 2019).…”