Endocrine Abstracts (2006) 11 S31

Dietary restriction and altered insulin/Igf1 signalling: conserved mechanisms regulating lifespan in worms, flies and rodents

DJ Withers

University College London, London, United Kingdom.

It has long been recognised that caloric restriction extends lifespan in a broad range of organisms from nematodes to rodents. Furthermore, it has also been demonstrated that manipulation of components of the insulin and Igf1 signalling pathway also increases lifespan. These findings were initially made in C. elegans and Drosophila but more recently these observations have been extended to rodents. However, the processes underlying the alterations in lifespan seen with caloric restriction and reduced insulin signalling have yet to be fully elucidated. To investigate this question, we have adopted a comparative functional genomic approach utilising microarray gene expression and metabonomic analyses together with manipulation of insulin signalling and dietary intake in C. elegans, Drosophila and the mouse. Furthermore we are examining lifespan in a number of rodent models with altered insulin signalling. The mechanisms we have identified will be discussed and the use of C. elegans and Drosophila models to gain insights into mammalian physiology will be presented.

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