Identification of Mutations that Extend the Fission Yeast Schizosaccharomyces pombe Chronological Lifespan by a Novel Parallel Selection Approach

Chapter 1: Background, significance and specific aims Aging, lifespan and longevity: a general introduction Aging: an evolutionary perspective The free radical theory of aging Caloric restriction(definition), stress management and lifespan Mitochondrial activity, metabolism and aging Down-regulation of the target of mTOR(definition)-inhibiting drug studied for extending healthspan and lifespan." style="text-decoration:underline dotted; text-underline-offset:2px; cursor:help;">rapamycin(definition) (TOR) signaling and longevity The insulin/insulin-like growth factor (IGF)-1 signaling and longevity Sir proteins (sirtuins) and aging: more than just silencing transcription Advantages of using yeast as a model to study evolutionarily conserved mechanisms of aging The fission yeast Schizosaccharomyces pombe as an emerging model to study aging and longevity Significance and specific aims of this study Chapter 2: A new Schizosaccharomyces pombe chronological lifespan assay reveals that caloric restriction promotes efficient cell cycle exit and extends longevity Abstract Introduction Materials and Methods S. pombe strains Chronological aging assays Analysis of CLS assay data FACS analysis (fixed cells) i FACS analysis (live cells) Stress sensitivity assays Results Chronological lifespan assay design Cells in SD medium show the evolutionarily conserved lifespan shortening in response to over nutrition while cells in EMM medium do not Caloric restriction extends lifespan in the SD medium-based assay Longer CLS correlates with exhausting free glucose in the medium Long-lived calorically restricted cells show increased stress resistanceThe AKT orthologs sck1 + and sck2 + differentially affect lifespan under normal and over nutrition conditions Deletions of the non-essential TOR kinase tor1 + or its potential substrate gad8 + extends S. pombe chronological lifespan