**7. Conclusion**

Recent studies in different model organisms, including *C. elegans*, *Drosophila melanogaster* and *Mus musculus* have generated piling knowledge about the IIS pathway and its relevance for healthy ageing and longevity. The data obtained in these model organisms have been translated to humans and lead to the identification of the IIS pathway as regulator for human lifespan and ageing.

The GH and IGF-1 signalling pathway plays a key-role in regulating growth and metabolism, and alterations within this pathway have crucial effects on health and lifespan. Model-organisms with reduced GH or IGF-1 signalling are frequently long-lived or show an increased mean lifespan. Interestingly, serum GH and IGF-1 levels decrease with age, and this might be interpreted not solely as progressive failure of the hypothalamus-somatotrope axis but rather as protection for insulin resistance and malignancies.

IGF-1R signalling is required for normal brain development, and acute IGF-1 action might enhance cognitive functions and ameliorates ischemic or traumatic brain injuries. Additionally, recent studies demonstrate that IGF-1R signalling or the number of IGF-1Rs in the brain during early development determines metabolism and possibly age-associated diseases indicating a role of IGF-1 mediated signals as neuroendocrine regulator of health and lifespan.

Foxo-transcription factors have been identified as main downstream-target of IIS and seem to be essential for activating gene transcripton that mediates longevity. Furthermore, genomic screening of centenarians with different genetic background found matching SNPs or haplotypes in the FOXO3A gene suggesting a key-role of FOXO3A in influencing lifespan not only in model organisms but also in humans.

However, the role of IIS in AD still raises questions, as the impaired signalling might be cause or consequence of neurodegeneration.

Therapeutic approaches altering the IIS pathway might not only improve treatment of neurodegenerative disorders but provide a possibility to prevent ageing-associated diseases in the future.
