Sex and Reproductive Fitness Impacts Immunity and Healthspan
Kosaraju, Jagruti
(2024)
Sex and Reproductive Fitness Impacts Immunity and Healthspan.
Master's Thesis, University of Pittsburgh.
(Unpublished)
This is the latest version of this item.
Abstract
Crosstalk between reproductive and somatic signaling pathways influences aging across multiple species. In women, a longer reproductive span correlates with an extended lifespan and health span, and this benefit extends to male relatives of women with extended reproductive health span. However, the molecular genetic mechanisms linking reproductive health and longevity remain poorly understood.
Our lab utilizes the model organism Caenorhabditis elegans to study these genetic mechanisms. We focus on the conserved pro-fertility, pro-longevity gene tcer-1 in C. elegans, which encodes a transcription elongation and splicing factor essential for regulating gene expression. TCER-1 is involved in transcriptional elongation and splicing, processes necessary for producing properly processed mature mRNAs, thus enabling accurate gene expression, particularly in somatic tissues.
In C. elegans, removing the proliferating germline extends lifespan. Our lab has shown that tcer-1 is necessary for this longevity. Loss of tcer-1 impairs fertility and various aspects of reproductive health, but tcer-1 mutant hermaphrodites live longer than wild-type counterparts under multiple stressors, including Gram-positive and Gram-negative pathogens. Given the marked differences in lifespan and disease susceptibilities between women and men, we investigated how gender influences pathogen resistance and whether tcer-1 mutant males also show increased immunity against the human opportunistic pathogen Pseudomonas aeruginosa strain PA14.
To assess the impact of germline integrity on longevity and health, we also use C. elegans meiosis mutants. Our lab previously found that mutations in genes functioning at multiple stages of meiosis a germline-restricted, conserved process shorten lifespan, impair health span, and destabilize protein homeostasis. RNAseq analysis revealed that the transcriptional profiles of young meiosis mutants closely resemble those of old wild-type animals. These data identified genes involved in the Wingless signaling (Wnt) pathway among the differentially expressed genes in key, short-lived meiotic mutants. The Wnt pathway, conserved from hydra to humans, regulates crucial developmental aspects. We employed in vivo molecular genetic analyses to investigate how Wnt signaling is activated in response to meiosis dysfunction, the Wnt pathway elements involved in signaling meiosis dysfunction to somatic tissues, and the systemic dispersal of these signals.
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Details
| Item Type: |
University of Pittsburgh ETD
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| Status: |
Unpublished |
| Creators/Authors: |
| Creators | Email | Pitt Username | ORCID  |
|---|
| Kosaraju, Jagruti | jak521@pitt.edu | jak521@pitt.edu | |
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| ETD Committee: |
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| Date: |
26 June 2024 |
| Date Type: |
Publication |
| Defense Date: |
18 June 2024 |
| Approval Date: |
26 June 2024 |
| Submission Date: |
21 June 2024 |
| Access Restriction: |
2 year -- Restrict access to University of Pittsburgh for a period of 2 years. |
| Number of Pages: |
56 |
| Institution: |
University of Pittsburgh |
| Schools and Programs: |
School of Public Health > Human Genetics |
| Degree: |
MS - Master of Science |
| Thesis Type: |
Master's Thesis |
| Refereed: |
Yes |
| Uncontrolled Keywords: |
Reproductive signaling, somatic signaling, reproductive health, lifespan, health span, molecular genetic mechanisms, longevity, Caenorhabditis elegans, genetic mechanisms, pro-fertility, pro-longevity, tcer-1 gene, transcription elongation, splicing factor, gene expressions, somatic tissues, germline, longevity, fertility, , tcer-1 gender influences, pathogen resistance, Pseudomonas aeruginosa, germline integrity, meiosis mutants, lifespan, health span, , Wingless signaling pathway (Wnt pathway), in vivo molecular genetic analyses, meiosis dysfunction. |
| Date Deposited: |
26 Jun 2024 19:42 |
| Last Modified: |
26 Jun 2024 19:42 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/46605 |
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Sex and Reproductive Fitness Impacts Immunity and Healthspan. (deposited 26 Jun 2024 19:42)
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