Calendar life span versus budding lifespan of Saccharomyces cerevisiae

Müller, Ilse; Zimmermann, Monika; Becker, Doris; Flömer, Marlies

doi:10.1016/0047-6374(80)90028-7

Cited by 156 publications

(82 citation statements)

References 9 publications

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“…Finally, disruption of isp7 ϩ results in an inability to acquire normal stationary-phase physiology, which is manifested by the inability of the cells to withstand heat shock under stationary (nondividing/G 0 -like) conditions (42,62). The long-term viability of nondividing cells is also known as chronological longevity (63). Key players that determine chronological longevity are the TOR signaling pathway and amino acid homeostasis (32,64).…”

Section: Fig 10mentioning

confidence: 99%

Isp7 Is a Novel Regulator of Amino Acid Uptake in the TOR Signaling Pathway

Laor

Cohen

Pasmanik‐Chor

et al. 2014

Molecular and Cellular Biology

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c TOR proteins reside in two distinct complexes, TOR complexes 1 and 2 (TORC1 and TORC2), that are central for the regulation of cellular growth, proliferation, and survival. TOR is also the target for the immunosuppressive and anticancer drug rapamycin. In Schizosaccharomyces pombe, disruption of the TSC complex, mutations in which can lead to the tuberous sclerosis syndrome in humans, results in a rapamycin-sensitive phenotype under poor nitrogen conditions. We show here that the sensitivity to rapamycin is mediated via inhibition of TORC1 and suppressed by overexpression of isp7 ؉ , a member of the family of 2-oxoglutarate-Fe(II)-dependent oxygenase genes. The transcript level of isp7 ؉ is negatively regulated by TORC1 but positively regulated by TORC2. Yet we find extensive similarity between the transcriptome of cells disrupted for isp7؉ and cells mutated in the catalytic subunit of TORC1. Moreover, Isp7 regulates amino acid permease expression in a fashion similar to that of TORC1 and opposite that of TORC2. Overexpression of isp7 ؉ induces TORC1-dependent phosphorylation of ribosomal protein Rps6 while inhibiting TORC2-dependent phosphorylation and activation of the AGC-like kinase Gad8. Taken together, our findings suggest a central role for Isp7 in amino acid homeostasis and the presence of isp7 ؉ -dependent regulatory loops that affect both TORC1 and TORC2.

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Section: Fig 10mentioning

confidence: 99%

Isp7 Is a Novel Regulator of Amino Acid Uptake in the TOR Signaling Pathway

Laor

Cohen

Pasmanik‐Chor

et al. 2014

Molecular and Cellular Biology

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“…Comparing RLS to viability in liquid culture: For the past 50 years, RLS in S. cerevisiae has been measured using the metric of cell divisions rather than time, on the basis of the observation that perturbations such as temperature change drastically alter division rate without affecting the median number of generations (Muller et al 1980). This metric also introduces an essential element for micromanipulation, since it allows one to interrupt a life span analysis nightly by moving the cells to 4°.…”

Section: Discussionmentioning

confidence: 99%

The Mother Enrichment Program: A Genetic System for Facile Replicative Life Span Analysis in Saccharomyces cerevisiae

2009

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The replicative life span (RLS) of Saccharomyces cerevisiae has been established as a model for the genetic regulation of longevity despite the inherent difficulty of the RLS assay, which requires separation of mother and daughter cells by micromanipulation after every division. Here we present the mother enrichment program (MEP), an inducible genetic system in which mother cells maintain a normal RLS-a median of 36 generations in the diploid MEP strain-while the proliferative potential of daughter cells is eliminated. Thus, the viability of a population over time becomes a function of RLS, and it displays features of a survival curve such as changes in hazard rate with age. We show that viability of mother cells in liquid culture is regulated by SIR2 and FOB1, two opposing regulators of RLS in yeast. We demonstrate that viability curves of these short-and long-lived strains can be easily distinguished from wild type, using a colony formation assay. This provides a simplified screening method for identifying genetic or environmental factors that regulate RLS. Additionally, the MEP can provide a cohort of cells at any stage of their life span for the analysis of ageassociated phenotypes. These capabilities effectively remove the hurdles presented by RLS analysis that have hindered S. cerevisiae aging studies since their inception 50 years ago.

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“…Yeast has many advantages for replicative aging studies, such as its short life span, completely sequenced genome, and well-characterized biology. Individual yeast cells are mortal, and their life span is measured by the number of times they divide, i.e., the number of daughter cells produced by a single mother (Mortimer and Johnston, 1959;Muller et al, 1980). These daughter cells have the potential for a full life span, whereas the mother cell increases in age with each cell division; thus, yeast aging is asymmetric.…”

Section: Introductionmentioning

confidence: 99%

The Transcriptome of Prematurely Aging Yeast Cells Is Similar to That of Telomerase-deficient Cells

Lesur

Campbell

2004

MBoC

116

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To help define the pathologies associated with yeast cells as they age, we analyzed the transcriptome of young and old cells isolated by elutriation, which allows isolation of biochemical quantities of old cells much further advanced in their life span than old cells prepared by the biotin-streptavidin method. Both 18-generation-old wild-type yeast and 8-generation-old cells from a prematurely aging mutant (dna2-1), with a defect in DNA replication, were evaluated. Genes involved in gluconeogenesis, the glyoxylate cycle, lipid metabolism, and glycogen production are induced in old cells, signifying a shift toward energy storage. We observed a much more extensive generalized stress response known as the environmental stress response (ESR), than observed previously in biotin-streptavidin-isolated cells, perhaps because the elutriated cells were further advanced in their life span. In addition, there was induction of DNA repair genes that fall in the so-called DNA damage "signature" set. In the dna2-1 mutant, energy production genes were also induced. The response in the dna2-1 strain is similar to the telomerase delete response, genes whose expression changes during cellular senescence in telomerase-deficient cells. We propose that these results suggest, albeit indirectly, that old cells are responding to genome instability. INTRODUCTIONMuch aging research is aimed at identifying the processes that lead to the generation of age-related cellular damage and understanding exactly how and where this damage occurs. Recently, there has been renewed focus on model organisms, such as the budding yeast Saccharomyces cerevisiae, for experimental work on aging. Yeast provides a model for contributions to aging made by tissues and organs that consist of constantly proliferating cells, replicative aging. Yeast has many advantages for replicative aging studies, such as its short life span, completely sequenced genome, and well-characterized biology. Individual yeast cells are mortal, and their life span is measured by the number of times they divide, i.e., the number of daughter cells produced by a single mother (Mortimer and Johnston, 1959;Muller et al., 1980). These daughter cells have the potential for a full life span, whereas the mother cell increases in age with each cell division; thus, yeast aging is asymmetric. The probability that an individual yeast cell will produce daughters declines exponentially as a function of its age in cell divisions or generations (Jazwinski et al., 1998). As yeast cells age, their size increases (Mortimer and Johnston, 1959;Nestelbacher, 2000), their cell cycle slows down (Mortimer and Johnston, 1959), their shape is altered (Pichova et al., 1997), their nucleolus tends to be larger and/or more fragmented, and they become sterile (Guarente, 1997). In wild-type cells, extrachromosomal ribosomal DNA circles (ERCs) also accumulate . Cells in the second half of their life span also show a switch to a state inducing increase loss of heterozygosity (LOH) (McMurray and Gottschling, 2003). Although...

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Calendar life span versus budding lifespan of Saccharomyces cerevisiae

Cited by 156 publications

References 9 publications

Isp7 Is a Novel Regulator of Amino Acid Uptake in the TOR Signaling Pathway

Isp7 Is a Novel Regulator of Amino Acid Uptake in the TOR Signaling Pathway

The Mother Enrichment Program: A Genetic System for Facile Replicative Life Span Analysis in Saccharomyces cerevisiae

The Transcriptome of Prematurely Aging Yeast Cells Is Similar to That of Telomerase-deficient Cells

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