On why decreasing protein synthesis can increase lifespan.
An explanation is offered for the increased lifespan of Caenorhabditis elegans when mRNA translation is inhibited due to loss of the initiation factor IFE-2 [Hansen, M., Taubert, T., Crawford, D., Libina, N., Lee, S.-J., Kenyon, C., 2007. Lifespan extension by conditions that inhibit translation in Caenorhabditis elegans. Ageing Cell 6, 95-110; Pan, K.Z., Palter, J.E., Rogers, A.N., Olsen, A., Chen, D., Lithgow, G.J., Kapahi, P., 2007. Inhibition of mRNA translation extends lifespan in Caenorhabditis elegans. Ageing Cell 6, 111-119; Syntichaki, P., Troulinaki, K., Tavernarakis, N., 2007. eIF4E function in somatic cells modulates ageing in Caenorhabditis elegans. Nature 445, 922-926]. It is suggested that the general reduction of protein synthesis, due to the decreased frequency of mRNA translation, also lowers the cellular load of erroneously synthesized polypeptides which the constitutive protein homeostatic apparatus (proteases and chaperones proteins) normally eliminates. This situation results in "spare" proteolytic and chaperone function which can then deal with those proteins modified post-synthetically, e.g. by oxidation and/or glycation, which are thought to contribute to the senescent phenotype. This increased availability of proteolytic and chaperone functions may thereby contribute to the observed increase in organism stress resistance and lifespan.
Hipkiss
Alan R
AR
Centre for Experimental Therapeutics, William Harvey Research Institute, John Vane Science Centre, Bart's and the London Queen Mary's School of Medicine and Dentistry, Charterhouse Square, London EC1M 6BQ, UK. alanandjill@lineone.net
D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000502:physiology*; D008136:Longevity / Q000235:genetics*; D010084:Oxidation-Reduction; D014176:Protein Biosynthesis / Q000235:genetics*; D017510:Protein Folding; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
D029742:Caenorhabditis elegans Proteins; C492705:IFF-2 protein, C elegans; D012333:RNA, Messenger