Degree Name

PhD (Doctor of Philosophy)

Program

Biomedical Sciences

Date of Award

5-2026

Committee Chair or Co-Chairs

Lev Yampolsky

Committee Members

Patrick Bradshaw, Melissa Whitaker, Philip Scheuerman, David Roane

Abstract

Although trade-offs between longevity and reproduction have been described for a long time, the genetic mechanisms by which organisms modulate allocation of resources between these two essential processes remain poorly understood, due to their complex nature and their modification by existing nutritional states and environmental cues. Daphnia magna represents a valuable model for investigation in this area due to their moderate lifespan and cyclic parthenogenetic mode of reproduction, allowing for the easy study of gene by environment interactions. This dissertation first investigates the change in mortality, reproduction, activity, and gene expression when fully fed Daphnia and calorically restricted Daphnia are given small molecule treatments meant to mimic caloric restriction – an intervention long known to extend lifespan across taxa. Daphnia on a fully fed diet experienced a reduction in mortality when given D-beta-hydroxybutyrate (BHB), a ketone body produced under limited glucose supply which is thought to be a potential mediator of the lifespan extension seen under caloric restriction. Daphnia on an already restricted diet experienced no decrease in mortality with BHB, but instead saw an increase in reproduction, suggesting that this molecule is able to exert effects on parallel life history trait pathways depending on existing nutritional state. No benefit to life history traits was observed with the addition of nicotinamide mononucleotide (NMN), a precursor to NAD+ which has also been theorized to mediate lifespan extension under limited food supply, however, NMN supplementation improved late-life activity levels. This dissertation then uses a novel transcriptomic technique (single nuclei RNA sequencing or snRNAseq) in order to examine the internal factors underlying a spontaneous rejuvenation of reproduction seen in a subset of aged Daphnia. The first snRNAseq atlas of Daphnia magna is presented, and genes which experience significant differential regulation between young and old Daphnia, and reproducing and non-reproducing Daphnia are identified and discussed. This work provides a basis for translational research into medical interventions to improve health, fertility, and longevity, as well as deepening our understanding of the evolution of these resource allocation pathways.

Document Type

Dissertation - unrestricted

Copyright

Copyright 2026 by Catherine Pearson

Included in

Biology Commons

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