title: Extension of yeast chronological lifespan by methylamine.
abstract: BACKGROUND
  Chronological aging of yeast cells is commonly used as a model for aging of human post-mitotic cells. The yeast Saccharomyces cerevisiae grown on glucose in the presence of ammonium sulphate is mainly used in yeast aging research. We have analyzed chronological aging of the yeast Hansenula polymorpha grown at conditions that require primary peroxisome metabolism for growth.
  
  
  RESULTS
  The chronological lifespan of H. polymorpha is strongly enhanced when cells are grown on methanol or ethanol, metabolized by peroxisome enzymes, relative to growth on glucose that does not require peroxisomes. The short lifespan of H. polymorpha on glucose is mainly due to medium acidification, whereas most likely ROS do not play an important role. Growth of cells on methanol/methylamine instead of methanol/ammonium sulphate resulted in further lifespan enhancement. This was unrelated to medium acidification. We show that oxidation of methylamine by peroxisomal amine oxidase at carbon starvation conditions is responsible for lifespan extension. The methylamine oxidation product formaldehyde is further oxidized resulting in NADH generation, which contributes to increased ATP generation and reduction of ROS levels in the stationary phase.
  
  
  CONCLUSIONS
  We conclude that primary peroxisome metabolism enhanced chronological lifespan of H. polymorpha. Moreover, the possibility to generate NADH at carbon starvation conditions by an organic nitrogen source supports further extension of the lifespan of the cell. Consequently, the interpretation of CLS analyses in yeast should include possible effects on the energy status of the cell.
authors.affiliation: Molecular Cell Biology, Groningen Biomolecular Sciences and Biotechnology Institute (GBB), University of Groningen, Kluyver Centre for Genomics of Industrial Fermentation, Groningen, The Netherlands.
authors.forename: Sanjeev
authors.initials: S
authors.lastname: Kumar
authors.forename: Sophie D
authors.initials: SD
authors.lastname: Lefevre
authors.forename: Marten
authors.initials: M
authors.lastname: Veenhuis
authors.forename: Ida J
authors.initials: IJ
authors.lastname: van der Klei
mesh_terms: D000409:Alanine / Q000494:pharmacology; D001483:Base Sequence; D002021:Buffers; D000431:Ethanol / Q000737:chemistry; D005947:Glucose / Q000737:chemistry; D006921:Hygromycin B / Q000494:pharmacology; D000432:Methanol / Q000737:chemistry; D008744:Methylamines / Q000737:chemistry / Q000494:pharmacology*; D008969:Molecular Sequence Data; D009243:NAD / Q000737:chemistry; D009584:Nitrogen / Q000737:chemistry; D020675:Peroxisomes / Q000378:metabolism; D010843:Pichia / Q000235:genetics / Q000378:metabolism*; D017382:Reactive Oxygen Species; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D013997:Time Factors
chemical_list: D002021:Buffers; D008744:Methylamines; D017382:Reactive Oxygen Species; D009243:NAD; D000431:Ethanol; D006921:Hygromycin B; C027451:methylamine; D005947:Glucose; D009584:Nitrogen; D000409:Alanine; D000432:Methanol