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The Role of Meiotic Genes in Regulating Somatic Aging in C. elegans

Loose, Julia (2022) The Role of Meiotic Genes in Regulating Somatic Aging in C. elegans. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

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Abstract

Reproduction and longevity have a complex relationship due to the resources needed for procreation and somatic maintenance of an aging organism. There is evidence in many species that reproduction can be harmful to the health of the organism and detrimental for longevity. However, there is also evidence to suggest that reproduction can be advantageous beyond the evolutionary benefit of species propagation, and can improve maternal health and longevity. Many of these studies, especially in human populations, are strictly correlative and there is a lack of understanding of causation and mechanisms. We were interested in determining if the health of the germ line has a causative role in the overall health and aging of an organism. C. elegans have proven to be a powerful model system to study the biology of aging and reproduction. Here we utilized these strengths of C. elegans, to explore the relationship between germ line integrity and longevity. We discovered that multiple mutations in the germline-specific process of meiosis shorten the lifespan in C. elegans. In detailed analysis of three meiotic genes, HTP-3, a component of the synaptonemal complex, SPO-11, an enzyme functioning during double-strand break formation along with DSB-2, revealed that this lifespan shortening is also accompanied with accelerated aging and impaired healthspan of the animal. We found that these meiotic mutants shared their transcriptomic profiles with older C. elegans and the transcriptomes of aging human tissues, underscoring the role of these genes in controlling aging. Through mechanistic explorations, we identified somatic protein aggregation as a potential downstream target through which SPO-11 and HTP-3 impact aging. These results demonstrate that the integrity of the germ line has a causative role in the maintenance of somatic aging and broaden our understanding of the relationship between reproduction and longevity.


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Details

Item Type: University of Pittsburgh ETD
Status: Unpublished
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Loose, Juliajal260@pitt.edujal2600000-0001-6226-9177
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Thesis AdvisorGhazi, Arjumandarjumand.ghazi@chp.edu
Committee ChairYanowitz, Judithyanowitzjl@mwri.magee.edu
Committee MemberBernstein, Karakarab@pitt.edu
Committee MemberNicotra, Matthewmatthew.nicotra@pitt.edu
Committee MemberOrwig, Kyleorwigke@upmc.edu
Date: 8 March 2022
Date Type: Publication
Defense Date: 18 February 2022
Approval Date: 8 March 2022
Submission Date: 2 March 2022
Access Restriction: 1 year -- Restrict access to University of Pittsburgh for a period of 1 year.
Number of Pages: 177
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: C. elegans, aging, reproduction
Date Deposited: 09 Mar 2022 03:37
Last Modified: 09 Mar 2022 03:37
URI: http://d-scholarship.pitt.edu/id/eprint/42288

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