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Metabolic Networks that Link Longevity to Reproduction in Response to Nutrition (MeLiLoN)
Start date: 01 Oct 2015, End date: 30 Sep 2020 PROJECT  ONGOING 

In most western countries, life expectancy is increasing by 3 months a year. As the average age of the population increases, so too does the prevalence of age-related diseases such as cancer, cardiovascular and metabolic diseases, and neurodegenerative disorders. An essential component of ageing research is to understand the biological mechanisms that contribute to the ageing process at the cellular and molecular levels. This has major implications not only for the treatment of age-associated diseases but also for the promotion of healthy ageing.Studies of experimental animals and observations in humans have identified an array of genes and nutritional conditions that increase lifespan. However, these manipulations (genetic or nutritional) often have detrimental effects on other biological processes; for example, reproduction, metabolism, immunity or growth. This is an area of ageing research that has largely been ignored but that is critical to the success of strategies intended to slow ageing and thus the onset of disease.The primary goal of this research proposal is to understand how lifespan extension is linked to reproduction. We will use the nematode Caenorhabditis elegans as a model organism to identify novel conserved genes, molecules, and metabolic networks that link reproduction and longevity through nutrition. The proposed study is based on a unique set of preliminary data that identifies the first clear molecular links between these traits: a steroid hormone receptor and a reproduction-responsive lipase, both of which modulate lifespan extension achieved through changes in nutrition.Understanding the regulation and function of these genes and pathways will clarify at the molecular level how reproduction is linked to longevity. This may ultimately lead to interventions that optimise metabolic activity to promote healthy ageing.
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