Why Longevity-Enhancing Genes are Not Selected by Evolution

Longevity may or may not be advantageous from an evolutionary point of view - it depends on the circumstances, which is why we see a wide variety of life spans in nature. Many species can be genetically altered in minor ways to live for longer in good health. One possible reason why these longevity-enhancing mutations don't occur in nature is that they may diminish an organism's reproductive vigor while young: "Reduced fecundity has been associated with some alleles that enhance longevity in invertebrate and mammalian models. This observation has been suggested to support the antagonistic pleiotropy theory of aging, which predicts that alleles of some genes promoting fitness early in life have detrimental effects later in life that limit survival. In only a few cases, however, has the relative fitness of long-lived mutants been quantified through direct competition with the wild type genotype. Here we report the first comprehensive analysis of longevity/fitness trade-offs by measuring the relative fitness of 49 long-lived yeast variants in a direct competition assay with wild type cells. We find that 32 (65%) of these variants show a significant defect in fitness in this competition assay. In 26 (81%) of these cases, this reduction in fitness can be partially accounted for by reduced maximal growth rate during early life, usually resulting from a G0/G1-specific cell cycle defect. A majority of the less fit longevity-enhancing variants are associated with reduced mRNA translation. These findings are therefore consistent with the idea that enhanced longevity often comes with a fitness cost and suggest that this cost is often associated with variation in a subset of longevity factors, such as those regulating mRNA translation, growth, and reproduction."

Link: http://www.ncbi.nlm.nih.gov/pubmed/21191185


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