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Chronological Aging in Saccharomyces cerevisiae

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Aging Research in Yeast

Part of the book series: Subcellular Biochemistry ((SCBI,volume 57))

Abstract

The two paradigms to study aging in Saccharomyces cerevisiae are the chronological life span (CLS) and the replicative life span (RLS). The chronological life span is a measure of the mean and maximum survival time of non-dividing yeast populations while the replicative life span is based on the mean and maximum number of daughter cells generated by an individual mother cell before cell division stops irreversibly. Here we review the principal discoveries associated with yeast chronological aging and how they are contributing to the understanding of the aging process and of the molecular mechanisms that may lead to healthy aging in mammals. We will focus on the mechanisms of life span regulation by the Tor/Sch9 and the Ras/adenylate cyclase/PKA pathways with particular emphasis on those implicating age-dependent oxidative stress and DNA damage/repair .

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Author information

Authors and Affiliations

  1. Department of Biological Sciences, Andrus Gerontology Center, University of Southern California, Los Angeles, CA, 90089-0191, USA

    Valter D. Longo

  2. Laboratory of Molecular and Cellular Biology, UMR5239 CNRS, Ecole Normale Supérieure de Lyon, Lyon, France

    Paola Fabrizio

Authors
  1. Valter D. Longo
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  2. Paola Fabrizio
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Corresponding authors

Correspondence to Valter D. Longo or Paola Fabrizio .

Editor information

Editors and Affiliations

  1. , Department of Cell Biology, University of Salzburg, Hellbrunnerstrasse 34, Salzburg, 5020, Austria

    Michael Breitenbach

  2. , Tulane Center for Aging and Department o, Tulane University Health Sciences Center, Tulane Avenue SL-12 1430, New Orleans, 70112, Louisiana, USA

    S. Michal Jazwinski

  3. , Department of Cell Biology, University of Salzburg, Hellbrunnerstrasse 34, Salzburg, 5020, Austria

    Peter Laun

Appendix

Appendix

While this book was in production we published two articles relevant to the topic of this chapter. For the sake of completeness, we believe it is appropriate to discuss them briefly here. The first article has reported the results of a screen of the yeast deletion collection aimed at identifying novel life span determinants (Fabrizio et al. 2010). Besides confirming the importance of the mitochondrial function and the autophagic process in long-term survival, our screen has uncovered numerous novel genes involved in the process of determining yeast longevity. Among others ACB1, CKA2, and TRM9. The deletion of each of these three genes prolongs life span and increases heat resistance. ACB1 codes an acyl-coA binding protein involved in lipid biosynthesis and vesicle formation. Cka2 is the catalytic subunit of a serine-threonine kinase, CK2, which controls several cellular functions including cell growth and proliferation. Trm9 is a tRNA methylase that targets the uridine residues at the wobble position in tRNA(Glu) and tRNA(Arg3). Currently, the mechanisms by which these proteins regulate longevity have not been described. It will be important to elucidate them given the high degree of conservation of these novel life span determinants and the possibility that their role in aging extends to other organisms.

The second article concerns the role of the conserved pro-aging pathways in the regulation of genomic instability and cancer. In the section “Conserved Pro-aging Genes, Genomic Instability, and Cancer” we have discussed how the activity of the Sch9 and GH/IGF-I pathways promotes DNA damage in yeast and mice, respectively. We have also mentioned that GH/IGF-I-deficient mice show decreased rates of cancer incidence. Recently this observation has been extended to humans with growth hormone receptor deficiency who display a major reduction in cancer and diabetes, which is associated with reduced levels of several orthologs of the key yeast pro-aging genes (Guevara-Aguirre et al. 2011). Importantly, serum from GH/IGF-I signaling-deficient individuals protects cells in culture from H2O2-dependent DNA damage and down-regulates the expression of N-Ras, PKA, and TOR while activating SOD2 transcription. This suggests that a reduction of GH/IGF-I signaling may lead to cellular protection and reduced DNA damage in vivo via the inactivation of the pro-aging Ras, PKA, and TOR pathways, which in turn may contribute to lower incidence of cancer and other diseases. Thus, this new evidence from a human study further supports a causative link between the activity of the conserved pro-aging pathways, genomic instability, and diseases.

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Longo, V.D., Fabrizio, P. (2011). Chronological Aging in Saccharomyces cerevisiae . In: Breitenbach, M., Jazwinski, S., Laun, P. (eds) Aging Research in Yeast. Subcellular Biochemistry, vol 57. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-2561-4_5

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