**6. IGF-1 in the brain and ageing**

IR/IGF-1R signalling is a conserved pathway functioning in development, fertility (Liang et al. 2003; Tatar, Bartke, and Antebi 2003; Broughton et al. 2005), growth (Butler and Le Roith 2001; Ikeya et al. 2002) and metabolic regulation (Saltiel and Kahn 2001). Decreased IR/IGF-1R signalling causes lifespan extension in model organisms like *Drosophila melanogaster*, *Caenorhabditis elegans* and *Mus musculus* (Clancy et al. 2001; Holzenberger et al. 2003; Tatar et al. 2001).

The life expenctancy of humans has been increased upon environmental amelioration (Wilmoth 2000). However, this is accompanied by an increase of age associated disorders. Therefore, the study of the molecular mechanism of ageing might lead to identification of disease modifying pathways. One of these pathways is the IR/IGF-1R signalling cascade. Studies investigating temporal or spatial restricted changes of the IR/IGF-1R signalling pathway in different model organisms, using the RU486-induced GAL4/UAS (upstream activation sequence) in *Drosophila*, as well as RNAi (RNA interference) incorparation via feeding of bacteria to *C. elegans* and Cre/loxP system in mice (Roman et al. 2001; Sauer 1998), have been performed.

The CNS is responsible for endocrine release of insulin-like peptides which activate the IR/IGF-1R signalling cascade and subsequently shorten lifespan (Ikeya et al. 2002; Broughton et al. 2005). Confusingly, acute increase of IR/IGF1-R signalling is neuroprotective but reduction of the signalling causes lifespan extension (Bateman and McNeill 2006; Chrysis et al. 2001).
