Longevity genes across species: Conservation versus evolvability

The search for longevity genes has greatly developed in recent years basing on the idea that a consistent part of longevity is determined by genetics. The ultimate goal of this research is to identify possible genetic determinants of human aging and longevity, but studies on humans are limited by a series of critical restrictions. For this reason, most of the studies in this field have been, and still are, performed on animal models, basing on the assumption that fundamental biological mechanisms are highly conserved throughout evolution and that, accordingly, extrapolation from model systems to humans is quite reasonable. Indeed, many comparative data obtained on single genes or gene families fit with this assumption. However, it is also clear that, despite such a basic conservative scenario, major changes also occurred in evolution, particularly regarding biological regulatory processes and integration between and among pathways. This consideration raises the fundamental question of the transferability of the results obtained from model systems to humans. In this review, we discuss the differences between animal models and men regarding the genetics of aging and longevity, and the possible reasons that can explain such discrepancies, with a particular emphasis on the phenomena of conservation and evolvability of biological systems. Finally we will suggest a possible strategy to identify putative longevity genes basing on their position inside conserved metabolic structures.