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Understanding the interplay of insulin/IGF signalling with endocrine hormones in ageing


The aim of the proposed research is to understand how Insulin/IGF signalling (IIS) interplays with other major hormone systems in Drosophila ageing. Ageing is a decline in survival probability and reproduction with advancing age. Reductions in IIS have bee n shown to extend lifespan and to reduce fecundity in invertebrates and mammals. I propose to use the power of molecular genetic manipulation and demographic measurements to determine how the cellular and systemic elements of IIS, ecdysone and juvenile hormone signalling regulate ageing and fecundity in Drosophila.

The insulin-like peptides of Drosophila (DILPs) are peptide hormone expressed in neurosecretory cells (NSCs) in the brain. Their expression is affected by nutrients, and regulates growth, glucose metabolism, reproduction and aging. The steroid hormone ecdysone and the sesquiterpenoid Juvenile hormone (JH) were discovered originally as molting hormones, but also influence reproduction and ageing in the adult. The mechanisms by which these hormonal systems interact, and how they regulate ageing and fecundity are not understood.

The proposed research project has two objectives:
1. To assess the interactions between IIS and ecdysone signalling in the determination of lifespan and fecundity in Drosophila:
(a) Does ECD signalling affects IIS or DILP-production and
(b) Does IIS affects the production of ECD in the ovary or elsewhere.
2. To assess regulation of juvenile hormone (JH) synthesis in the corpora allata (CA) by insulin/IGF-like signalling (IIS).

The results will be of direct relevance to human ageing, and could lead to the development of new drugs against obesity, diabetes and age-related decline in function.

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Gower Street
United Kingdom