Jekyll and Hyde, the p53 protein, pleiotropics antagonisms and the thrifty aged hypothesis of senescence

SummaryAntagonistic pleiotropy theory holds that ageing is a not selected trait, and only the consequence of genes fixed in evolution by their reproductive advantage early in life, but with harmful effects in the post reproductive period. Although the existence of antagonistic pleiotropic genes has been controversial, recent molecular approaches seem to confirm them. One of the proposed examples is p53, a gene that plays a pivotal role in the cell stress response. It has been pointed that p53 driven programs, apoptosis and cellular senescence, protect organisms from cancer early in life, but promote ageing phenotype in older members. On the other hand, recent evidences suggest that ageing is not a random program, but a carefully orchestrated one. Accordingly, the antagonistic pleiotropy theory as well as the ageing purpose must be updated. In this issue the p53 candidature to be an antagonistic pleiotropic gene is revisited. Moreover, it has been postulated that these kinds of genes could be actively selected by both effects, and not only by their reproductive advantage early in life, because they improve fitness and they contribute to structure ageing, a program that optimise the energy availability in the post reproductive state.