Although several life span-controlling genes have already been identifiedinflies,wormsandyeast,itisstillnotcleartowhatextent they account for variation that influences survival at advanced age in humans. With the identification of FOXO3A and EXO1 as modi- fiers of human longevity it was demonstrated for the first time that genetic information obtained from pathways in model organisms (i.e. IIS and DNA repair, respectively) can be translated to human ageing [18–21,29,59]. But as seen in this and other studies [12,60], most of the findings from laboratory organisms cannot be easily transferred. Since humans have acquired more diverse pathways, the signaling systems in these pathways have become more robust and are therefore more resistant to changes in their components or in the environment [12,61,62]. Moreover, the human genome often contains several homologues of a single invertebrate gene, which may compensate the function of the original gene, and is therefore more tolerant to a so-called mutation load [63]. Furthermore, envi- ronmentalinfluencescanleadtoadifferentexpressionofgenotypic information. Besides, human genetic longevity studies often con- centrate on genes that were identified in mutant model organisms living under laboratory conditions [12,64]. Hence, all these argu- ments suggest that the comparability of results between model organisms and humans might be limited.

Appendix A. Supplementary data

Supplementary data associated with this article can be found, in online version, at doi:10.1016/j.mrfmmm.2010.08.006.

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