ANALYSIS OF THE INTERPLAY BETWEEN THE SEXES WITH RESPECT TO REPRODUCTIVE AND SOMATIC AGING IN CAENORHABDITIS SPECIES

Abstract

Caenorhabditis elegans is an excellent model for somatic and reproductive aging. C. elegans hermaphrodites can reproduce by self-fertilization or by mating with males. Male sperm outcompete the hermaphrodite’s own sperm, significantly increasing the total progeny production and extending the period of reproduction. Self-reproduction is artificially limited by sperm number. Therefore, mated-reproductive span, which measures the rate of oocyte quality decline (the limiting factor for reproductive aging in both worms and mammals) is the gold standard to study reproductive aging in C. elegans. In the process of doing mated-reproductive span assays, I made the surprising finding that in both androdioecious (hermaphroditic and male) and gonochoristic (female and male) Caenorhabditis, mating leads to female shrinking and early death, dramatically compressing the post-reproductive lifespan. The underlying mechanism of post-mating lifespan decrease requires the FOXO transcription factor DAF-16 and is mediated by seminal fluid, while post-mating shrinking is induced by male sperm, requires germline proliferation, and is dependent on the nuclear hormone receptor DAF-12 and the DAF-9 cytochrome P450. Sperm-induced shrinking leads to reduced osmotic resistance, further decreasing the post-mating lifespan, which is additive to and independent of the DAF-16 mediated mechanism. Together, these findings uncovered a previously unknown example of sperm competition, and revealed a new short longevity state in C. elegans.

Mating is also costly to males. Using single worm assays, I discovered that males live significantly shorter after mating in both androdioecious and gonochoristic Caenorhabditis. Germline-dependent shrinking, glycogen loss, and ectopic expression of vitellogenins contribute to male post-mating lifespan reduction, which is conserved between the sexes. Moreover, worms are subject to killing by male pheromone-dependent toxicity. C. elegans males are the most sensitive, whereas C. remanei are immune, suggesting that males in androdioecious and gonochoristic species utilize male pheromone differently, either as a toxin or a chemical messenger. Our study reveals two mechanisms involved in male lifespan regulation: germline-dependent shrinking and death results from the unavoidable cost of reproduction and is evolutionarily conserved, whereas male pheromone-mediated killing occurs only in androdioecious species. Our work highlights the importance of understanding the shared vs. sex- and species-specific mechanisms that regulate lifespan.