Mnsod overexpression extends the yeast chronological (G(0)) life span but acts independently of Sir2p histone deacetylase to shorten the replicative life span of dividing cells.
Studies in Drosophila and Caenorhabditis elegans have shown increased longevity with the increased free radical scavenging that accompanies overexpression of oxidant-scavenging enzymes. This study used yeast, another model for aging research, to probe the effects of overexpressing the major activity protecting against superoxide generated by the mitochondrial respiratory chain. Manganese superoxide dismutase (MnSOD) overexpression increased chronological life span (optimized survival of stationary (G(0)) yeast over time), showing this is a survival ultimately limited by oxidative stress. In contrast, the same overexpression dramatically reduced the replicative life span of dividing cells (the number of daughter buds produced by each newly born mother cell). This reduction in the generational life span by MnSOD overexpression was greater than that generated by loss of the major redox-responsive regulator of the yeast replicative life span, NAD+-dependent Sir2p histone deacetylase. It was also independent of the latter activity. Expression of a mitochondrially targeted green fluorescent protein in the MnSOD overexpressor revealed that the old mother cells of this overexpressor, which had divided for a few generations, were defective in segregation of the mitochondrion from the mother to daughter. Mitochondrial defects are, therefore, the probable reason that MnSOD overexpression shortens replicative life span.
Harris
Nicholas
N
Department of Biochemistry and Molecular Biology, University College London, England, London, UK
Costa
Vitor
V
MacLean
Morag
M
Mollapour
Mehdi
M
Moradas-Ferreira
Pedro
P
Piper
Peter W
PW
D002455:Cell Division / Q000502:physiology; D016922:Cellular Senescence / Q000502:physiology*; D049452:Green Fluorescent Proteins; D006655:Histone Deacetylases / Q000378:metabolism*; D008136:Longevity / Q000235:genetics*; D008164:Luminescent Proteins / Q000378:metabolism; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D009243:NAD / Q000378:metabolism; D018384:Oxidative Stress; D012441:Saccharomyces cerevisiae / Q000502:physiology*; D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae / Q000378:metabolism*; D056565:Sirtuin 2; D037761:Sirtuins / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000378:metabolism*; D015854:Up-Regulation
D008164:Luminescent Proteins; D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae; D009243:NAD; D049452:Green Fluorescent Proteins; D013482:Superoxide Dismutase; C087778:SIR2 protein, S cerevisiae; D056565:Sirtuin 2; D037761:Sirtuins; D006655:Histone Deacetylases