Kern, Carina Carla; (2021) Ageing through reproductive death in Caenorhabditis elegans. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

The nematode worm Caenorhabditis elegans has emerged as one of the premier model systems for ageing research. Its use has led to the discovery of many biological mechanisms of ageing conserved across species, including acceleration of ageing by insulin/IGF-1 signalling (IIS) and germline signalling. Ageing in C. elegans, however, is unusual in terms of the severity and early onset of senescent pathology, particularly affecting organs involved in reproduction. For example, in post-reproductive hermaphrodites, intestinal biomass is converted into yolk leading to intestinal atrophy and yolk steatosis. While late yolk production has long been viewed as futile, is it possible that it somehow promote fitness? Results in this thesis show that post-reproductive C. elegans hermaphrodites vent yolk that can be consumed by larvae, promoting their growth. Thus, post-reproductive mothers can contribute to reproductive fitness by converting their biomass into milk, suggesting that intestinal atrophy is a cost of lactation. This type of massive reproductive effort involving biomass repurposing leading to organ degeneration is characteristic of semelparous organisms (i.e. that exhibit only a single reproductive episode) ranging from monocarpic plants to Pacific salmon where it leads to rapid death (reproductive death). Results also show that lactation occurs in other hermaphroditic Caenorhabditis nematode species but not in females. Moreover, the latter do not exhibit intestinal atrophy or steatosis, and are longer lived suggesting that they do not undergo reproductive death. Furthermore, germline ablation strongly increases lifespan in hermaphrodites but not females; similarly, blocking sexual maturation e.g. by gonadectomy can greatly increase lifespan in other organisms that undergo reproductive death. IIS which accelerates C. elegans ageing is also shown to promote lactation. These results suggest that C. elegans hermaphrodites exhibit reproductive death, suppression of which increases lifespan. This has major implications in terms of what one can learn about human ageing from C. elegans.

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