Comparative and transcriptomic examination of senescence in Pristionchus nematodes

Abstract

Healthspan, the period of life where the organism is without frailty or disease, is sought to be better understood and extended through many branches of biomedical research. One approach is using short-lived model organisms. Here, freeliving nematode worms Pristionchus pacificus and Pristionchus fissidentatus are used to conduct a comparative and transcriptomic examination of age-linked decline (senescence). In chapter 2, I find that various life history traits differ between P. pacificus and P. fissidentatus, including lifespan, making them useful to study intricate differences in ageing and longevity responses. I find several measurable traits that are healthspan indicators. In chapter 3, I identify differentially expressed genes between young adult and old worms to find age-linked molecular changes, identify where they are interspecifically consistent, and find species-specific signatures. These two chapters build a phenotypic and molecular ageing profile for P. pacificus and P. fissidentatus. In chapter 4, twelve promising interventions are assayed for healthspan effects using methods optimised in chapter 2. Most notably, I find that in P. pacificus, the effect of dietary restriction is dependent on the extent of reduced calorific intake, antifungal nystatin decreases lifespan and healthspan, and antioxidant hippuric acid improves healthspan. In chapter 5, I identify differentially expressed genes associated with these three interventions to explore which molecular mechanisms are disrupted to give life/healthspan changes. Overall, this is the first healthspan report for P. fissidentatus and demonstrates the potential of P. pacificus as a new ageing model. This work highlights similarities and differences in ageing of two Pristionchus nematodes and improve our understanding of both lifespan and healthspan change.