DOI

https://doi.org/10.25772/XTNS-YH68

Author ORCID Identifier

https://orcid.org/0009-0003-8127-2410

Defense Date

2025

Document Type

Thesis

Degree Name

Master of Science

Department

Biology

First Advisor

Kaya, Alaattin

Second Advisor

Jason Newton

Third Advisor

Sarah Rothschild

Abstract

The kynurenine pathway is a highly conserved pathway that acts as the primary pathway for tryptophan catabolism and has been found to be involved in lifespan regulation across many diverse organisms. Caloric restriction (CR) is the only known dietary intervention to date that both increases the mean lifespan and the health span of multiple organisms, although the molecular mechanisms of these effects are not fully understood. There are known and sometimes contradictory relationships between the kynurenine pathway activity and the life- extending effect of CR but the crosstalk between the two is not well characterized. Understanding these relationships could lead to interventions by which both lifespan and health span can be modulated. Our findings aim to identify genetic components of the kynurenine pathway that affect the lifespan extending effects of caloric restriction. We applied an RNAseq focused approach for identifying molecular changes mediated by kynurenine pathway deficiency under control and CR conditions and further assayed several phenotypic outcomes. As a result, we identified genes and pathways regulated by kynurenine pathways activity and found that decreased tryptophan catabolism is required or CR-mediated lifespan extension. Further research is needed to elucidate the lifespan altering effects of Kynurenine pathway activity in a dose dependent manner as it relates to the beneficial effects of CR.

Rights

© The Author

Is Part Of

VCU University Archives

Is Part Of

VCU Theses and Dissertations

Date of Submission

4-27-2025

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