Aging is an intrinsic process leading to the progressive decline in physiological functions. In response to environmental cues, genetically identical individuals in the ant species Harpegnathos saltator can switch to more than 5 times longer lifespan, with changes in reproduction and behavior. The worker to gamergate transition in the ant is analogous to cell de-differentiation and re-differentiation in somatic cell reprogramming, which involves critical changes in gene expression and chromatin structure. The fat body plays crucial roles in the physiological changes during the gamergate transition, including ovary activation, egg production and variation in pheromone (cuticular hydrocarbon) profiles. Therefore, tracking gene expression profiles in the fat body will help clarify how a worker switches to a gamergate and achieves longevity. The preliminary data of the fat body transcriptome shows interesting gene expression profiles in antioxidants, cell proliferation, pheromone synthesis and insulin signaling. The data is consistent with previous studies in other species, suggesting a common mechanism underlying longevity. I will first analyze the adult and larvae fat body transcriptomes and use fly genetics to study the biological functions of the differentially expressed genes (DEGs). Second, these DEGs also contain transcription factors (TFs), which play an important role in the initiation and maintenance of gene expression profiles in the fat body during the worker to gamergate transition. TFs with strong changes in the gamergate transition will be selected to identify their target genes using fly genetics and ChIP. In addition, I will search for the target genes of chromatin modifiers. Last, I will address how th fat body regulates ovary activation. The candidate gene IGF-1 is an insulin-like peptide (ilp) predominately expressed in the H. saltator fat body. Its function may be similar to Dilp6, which regulates ovary activation in Drosophila. To address the function of IGF-1, in vitro co-culture of the fat body and ovary will be performed. This effect will be tested immunohistochemically, using the cell mitosis marker phosphor-histone H3 (H3S10P). In addition, purified IGF- 1 protein will be directly added to the worker ovary culture followed by H3S10P staining to test for ovary activation. In summary, this project will address how longevity is achieved in the transition from non- reproductive workers to reproductive gamergates, and the role of the fat body in this transition. This study will provide novel insights into the regulatory mechanisms underlying longevity.

Public Health Relevance

Aging is an intrinsic process leading to progressive decline in the physiological conditions in humans and other organisms. The proposed study will use the distinct features in ants to understand the regulation of aging process.

National Institute of Health (NIH)
National Institute on Aging (NIA)
Postdoctoral Individual National Research Service Award (F32)
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Special Emphasis Panel (ZRG1-F05-D (21))
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Murthy, Mahadev
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New York University
Schools of Medicine
New York
United States
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