Naim, Nikki
(2022)
Molecular Mechanisms Controlling Immunity, Fertility, and Longevity.
Doctoral Dissertation, University of Pittsburgh.
(Unpublished)
Abstract
All organisms must balance their cellular resources to invest in life processes such as reproduction, immunity, and longevity to persist as a species. For this reason, animal fertility often wanes during an immune response and vice versa. Increased reproductive activity has also been associated with reduced lifespan in many species. Studies suggest that animals possess genetic mechanisms which coordinate such life history traits, yet, the molecular mechanisms underlying these reproduction-immunity-longevity (RIL) relationships remain largely unexplored. The nematode Caenorhabditis elegans is a model organism which has long been used to characterize conserved genetic regulators of reproduction, immunity, and longevity. Work from our laboratory, which identified that two C. elegans transcription factors, NHR-49 and TCER-1, impact RIL processes therefore opened avenues to investigate RIL coordination in animals. NHR-49, proposed functional homolog of the vertebrate protein, PPARα, is a nuclear hormone receptor noted to promote lifespan and lipid homeostasis. TCER-1, shown to promote lifespan and fertility, is the C. elegans homolog of the human transcription and elongation splicing factor, TCERG1. My work exploring RIL coordination by these factors has shown that NHR-49 promotes both immune resistance and longevity but acts in distinct tissues to regulate these traits. Studying TCER-1 revealed that the protein additionally suppresses immunity while promoting fertility, supporting previous hypotheses that TCER-1 enacts RIL tradeoffs. Further characterization based on these findings showed that TCER-1 likely promotes small RNA production to suppress immunity in fertile animals. The results of these projects therefore describe (a) new functions of well-studied proteins in the RIL dialogue, (b) new mechanisms of context-dependent regulation by these genes, and (c) new effectors of these pathways. These findings support emerging concepts in aging biology that genetic mechanisms which control reproduction, immunity, and longevity are both distinct and interconnected. For humans, these studies may uncover what immune mechanisms are suppressed in fertility and how to target drugs that improve health as well as lifespan.
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Details
| Item Type: |
University of Pittsburgh ETD
|
| Status: |
Unpublished |
| Creators/Authors: |
|
| ETD Committee: |
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| Date: |
7 March 2022 |
| Date Type: |
Publication |
| Defense Date: |
16 February 2022 |
| Approval Date: |
7 March 2022 |
| Submission Date: |
2 March 2022 |
| Access Restriction: |
2 year -- Restrict access to University of Pittsburgh for a period of 2 years. |
| Number of Pages: |
261 |
| Institution: |
University of Pittsburgh |
| Schools and Programs: |
School of Medicine > Molecular Genetics and Developmental Biology |
| Degree: |
PhD - Doctor of Philosophy |
| Thesis Type: |
Doctoral Dissertation |
| Refereed: |
Yes |
| Uncontrolled Keywords: |
Aging, Longevity, Immunity, Fertility, Reproduction, C. elegans |
| Date Deposited: |
08 Mar 2022 04:22 |
| Last Modified: |
07 Mar 2024 06:15 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/42286 |
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