| dc.description.abstract | Reproductive senescence is an important part of the aging process in animals, including in Drosophila melanogaster. Hormone signaling pathways such as insulin and insulin-like growth factor-like signaling (IIS) have well-characterized roles in aging and potentially also play a role in reproductive senescence. Most reproductive senescence studies have focused on only one sex, though both sexes display reproductive senescence. There are no studies that have investigated multiple tissues and age-specific differences in both sexes, such that direct comparisons can be made in Drosophila. This dissertation addresses these gaps by investigating how changes in gene expression and in hormone signaling pathways with age contribute to sex dimorphism in reproductive senescence examining reproductive and somatic tissue over time in male and female fruit flies, as well as the response to changes in diet. In Chapter 1, I have provided an extensive review of the insulin signaling pathway, its role in aging, and the known molecular mechanisms of reproductive senescence. I explained how this pathway helps maintain metabolism and how changes in it can affect aging and reproduction, especially under nutritional stress. I also discuss how sex dimorphism in aging may arise from variations in hormonal signaling and tissue-specific responses. Chapter 2 focuses on the role of the IIS pathway in reproductive aging in Drosophila, investigating how IIS gene expression changes across somatic and gonadal tissues during aging. I hypothesize that IIS gene expression shows age-specific alterations, which may contribute to reproductive senescence in males and females. Using Tag sequencing, I analyze gene expression changes at different ages and identify key pathways associated with immune response, metabolic regulation, and reproductive function. This study also showed a general increase in unbiased gene expression over time in somatic and reproductive tissues, consistent with desexualization. However, IIS genes showed inconsistent desexualization, suggesting strong functional constraints on sex-specific regulation in this pathway. In Chapter 3, I examined how protein and carbohydrate restriction affect the IIS pathway and reproduction in male and female Drosophila. Using both phenotypic and transcriptomic profiling assays, I observed that dietary stress accelerates reproductive aging. Females showed more reproductive output changes than males, especially under carbohydrate and protein-restricted diets. These findings highlight the sex-specific response to dietary stress and emphasize the involvement of the IIS pathway in mediating these effects. Furthermore, weighted gene co-expression network analysis (WGCNA) identified distinct gene modules associated with age, sex, tissue, and diet, providing new insight into the molecular pathways that regulate reproductive aging. Overall, the results from this dissertation highlight how dietary stress, sexual dimorphism, and sex-specific gene expression patterns influence IIS activity and contribute to reproductive senescence. | en_US |
