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Metabolic Networks that Link Longevity to Reproduction in Response to Nutrition

Investigator from French National Centre for Scientific Research (CNRS)

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European Commission (Belgium)
In most western countries, life expectancy is increasing by 3 months a year. As the average age ofthe population increases, so too does the prevalence of age-related diseases such as cancer, cardiovascularand metabolic diseases, and neurodegenerative disorders. An essential component of ageing research is tounderstand the biological mechanisms that contribute to the ageing process at the cellular and molecularlevels. This has major implications not only for the treatment of age-associated diseases but also for thepromotion of healthy ageing.Studies of experimental animals and observations in humans have identified an array of genes andnutritional conditions that increase lifespan. However, these manipulations (genetic or nutritional) oftenhave 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 thesuccess 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 novelconserved 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 firstclear molecular links between these traits: a steroid hormone receptor and a reproduction-responsivelipase, 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 molecularlevel how reproduction is linked to longevity. This may ultimately lead to interventions that optimisemetabolic activity to promote healthy ageing.

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