Dissertation
Nutrient regulation of proliferation and autophagy determines follicle stem cell lifespan
Doctor of Philosophy (Ph.D.), Drexel University
Nov 2019
DOI:
https://doi.org/10.17918/1ss3-be02
Abstract
A balanced diet is fundamental to promote health, longevity and delay aging. The impact of diet on health is mediated to a large degree through translation by adult stem cell populations that modulate tissue repair and maintenance throughout an organism's life. While research has uncovered some immediate effects of diet on stem cell activity, less is known about how specific nutrients balance the long-term survival of stem cells. Here, I investigated how dietary restriction (DR), cholesterol, glucose and essential amino acids (EAAs) modulate epithelial follicle stem cell (FSC) function and lifespan in the fly ovary. I show that DR, cholesterol, and glucose disrupt the functional balance between proliferation and autophagy in FSCs, with a direct impact on their lifespan. In contrast, EAAs restore this functional balance in FSCs to improve their retention with age. I demonstrate that deregulated nutrient signaling disrupts the diet-dependent effects on FSC lifespan in part via altering levels of insulin-like peptide (Ilp2) and target of rapamycin (Tor). Overall, these findings advance our understanding of the distinct mechanisms of action for individual nutrients in controlling somatic stem cell maintenance and female reproductive lifetime. These mechanisms will likely have important implications for understanding the meaning of dietary balance and how to achieve it at the cellular level in order to prevent reproductive aging.
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Details
- Title
- Nutrient regulation of proliferation and autophagy determines follicle stem cell lifespan
- Creators
- Sheila Mary Longo - Drexel University, Biochemistry and Molecular Biology
- Contributors
- Alana M. O'Reilly (Advisor) - Drexel University (1970-)Mauricio Reginato (Advisor) - Drexel University (1970-)
- Awarding Institution
- Drexel University
- Degree Awarded
- Doctor of Philosophy (Ph.D.)
- Publisher
- Drexel University; Philadelphia, Pennsylvania
- Number of pages
- xiii, 184 pages
- Resource Type
- Dissertation
- Language
- English
- Academic Unit
- Biochemistry and Molecular Biology; College of Medicine; Drexel University
- Other Identifier
- 11346; 991014632525804721