Increasing Saccharomyces cerevisiae stress resistance, through the overactivation of the heat shock response resulting f
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O R I GI N A L P A P E R
N. Harris á M. MacLean á K. Hatzianthis B. Panaretou á P. W. Piper
Increasing Saccharomyces cerevisiae stress resistance, through the overactivation of the heat shock response resulting from defects in the Hsp90 chaperone, does not extend replicative life span but can be associated with slower chronological ageing of nondividing cells Received: 15 June 2000 / Accepted: 7 November 2000 / Published online: 19 January 2001 Ó Springer-Verlag 2001
Abstract Recent studies on Drosophila and Caenorhabditis elegans indicate that increases in stress resistance result in a longer chronological life span, an eect that must operate primarily on the postmitotic tissues of the adult. Stress resistance can be increased through decreases in Hsp90 chaperone activity, since Hsp90 acts to downregulate the activity of heat shock transcription factor. This study investigated whether the increases in stress resistance associated with reduced Hsp90 chaperone activity in¯uence ageing in the budding yeast Saccharomyces cerevisiae, ageing being measured either as the replicative (nonchronological) senescence of budding cells or as the chronological ageing of non-dividing (stationary phase) cultures. Overactivation of the heat shock response caused no slowing of replicative senescence. In some situations though it was associated with a longer chronological life span of stationary cells, the yeast equivalent of the postmitotic state. This is consistent with the idea that stress resistance exerts its life span-extending eects primarily in postmitotic cells and tissues. Key words Ageing á Stress resistance á Replicative senescence á Chronological life span á Saccharomyces cerevisiae á Hsp90 á yeast Abbreviations HSF: heat shock transcription factor
Communicated by C. P. Hollenberg N. Harris á M. MacLean á K. Hatzianthis B. Panaretou á P. W. Piper (&) Department of Biochemistry and Molecular Biology, University College London, Gower Street, London WC1E 6BT, UK E-mail: [email protected] Tel.: +44-20-76792212 Fax: +44-20-76797193
Introduction Recently it has been shown that the life spans of certain model organisms can be increased by increases in stress resistance. The initial reports of the extension of Drosophila life-span by the insertion of transgenes coding for superoxide dismutase (Sod) plus catalase did not survive close scrutiny (Kaiser et al. 1996; Tower 1996). However, more recent work has shown that it is sucient just to increase the Cu/Zn-Sod levels in adult ¯ies (Sun and Tower 1999) or to express human Cu/Zn-Sod in their motorneurons (Parkes et al. 1998) in order to extend the life span of Drosophila. These ®ndings are consistent with the notion that, for most organisms, stress protection and repair systems are not optimised for maximisation of life span. They raise the important issue of why natural selection prevents the higher constitutive levels of expression of antioxidant defences, and perhaps heat shock proteins, which could maximise life spans (Lithgow 1996). Long-lived Drosophila can als
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