ORCID

http://orcid.org/0000-0002-8573-1376

Date of Award

Summer 8-15-2019

Author's School

Graduate School of Arts and Sciences

Author's Department

Biology & Biomedical Sciences (Molecular Genetics & Genomics)

Degree Name

Doctor of Philosophy (PhD)

Degree Type

Dissertation

Abstract

C. elegans hermaphrodites display dramatic age-related decline of reproduction early in life while somatic functions are still robust. To understand why the germline fails so early, we analyzed the assembly line of oocyte production that generates fertilized eggs in mated hermaphrodites with sufficient sperm. Aging germlines displayed both sporadic and population-wide changes. A small fraction of aging animals displayed endomitotic oocytes in the germline and other defects. By contrast, all animals displayed age-related decreases in germline size and function. As early as day 3 of adulthood, animals displayed fewer stem cells and a slower cell cycle, which combine to substantially decrease progenitor zone output. The C. elegans germline is the only adult tissue that contains stem cells, allowing the analysis of stem cells in aging. To investigate the mechanism of the decrease in stem cell number, we analyzed the Notch signaling pathway. The Notch effectors LST-1 and SYGL-1 displayed age-related decreases in expression domains, suggesting a role for Notch signaling in germline aging. The results indicate that while sporadic defects account for the sterility of some animals, population-wide changes account for the overall pattern of reproductive aging. Moderate caloric restriction and specific mutations in the insulin pathway result in extended reproductive span, albeit with decreased peak reproduction. We found that while the germline of these mutant animals started out smaller and meiotic entry was lower than in wild-type, the slope of decline was more gradual than in wild-type. This was consistent with the hypothesis that an age-related decrease in progenitor function leads to a decrease in meiotic entry and causes the age-related decrease in progeny production. We also identified mid-life reproductive improvement, a pattern of increased progeny production on days 5-7 of adulthood in che-3(lf) and sygl-1(tg), and found that certain mutants extended lifespan without compromising early progeny production and that other mutants increased reproductive ability without extending lifespan. These results showed that while reproductive function and somatic lifespan are inter-linked, they are also separable.

Language

English (en)

Chair and Committee

Kerry Kornfeld Tim Schedl

Committee Members

Tom Baranski, Kristen Kroll, Zachary Pincus, Joan Riley,

Comments

Permanent URL: https://doi.org/10.7936/my5m-r127

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