SIR2 and other genes are abundantly expressed in long-lived natural segregants for replicative aging of the budding yeast Saccharomyces cerevisiae

Guo, Zhenhua; Adomas, Aleksandra; Jackson, Erin D.; Qin, Hong; Townsend, Jeffrey P.

doi:10.1111/j.1567-1364.2011.00723.x

Cited by 10 publications

(6 citation statements)

References 93 publications

(103 reference statements)

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“…SIR2 has been found abundantly expressed in long-lived compared with short-lived yeast strains (Guo et al 2011). In addition, young cells contain greater than 10 times more Sir2p than older cells (Lindstrom et al 2011).…”

Section: Discussionmentioning

confidence: 99%

Natural genetic variation in yeast longevity

et al. 2012

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The genetics of aging in the yeast Saccharomyces cerevisiae has involved the manipulation of individual genes in laboratory strains. We have instituted a quantitative genetic analysis of the yeast replicative lifespan by sampling the natural genetic variation in a wild yeast isolate. Haploid segregants from a cross between a common laboratory strain (S288c) and a clinically derived strain (YJM145) were subjected to quantitative trait locus (QTL) analysis, using 3048 molecular markers across the genome. Five significant, replicative lifespan QTL were identified. Among them, QTL 1 on chromosome IV has the largest effect and contains SIR2, whose product differs by five amino acids in the parental strains. Reciprocal gene swap experiments showed that this gene is responsible for the majority of the effect of this QTL on lifespan. The QTL with the second-largest effect on longevity was QTL 5 on chromosome XII, and the bulk of the underlying genomic sequence contains multiple copies (100-150) of the rDNA. Substitution of the rDNA clusters of the parental strains indicated that they play a predominant role in the effect of this QTL on longevity. This effect does not appear to simply be a function of extrachromosomal ribosomal DNA circle production. The results support an interaction between SIR2 and the rDNA locus, which does not completely explain the effect of these loci on longevity. This study provides a glimpse of the complex genetic architecture of replicative lifespan in yeast and of the potential role of genetic variation hitherto unsampled in the laboratory.

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Section: Discussionmentioning

confidence: 99%

Natural genetic variation in yeast longevity

et al. 2012

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“…For example, moderate overexpression of SIR2 extends lifespan, and vice versa [ 11 ]. Moreover, natural variations in SIR2 expression correlate with strain longevity [ 74 , 75 ]. Finally, Sir2 protein levels and Sir2-dependent silencing decrease with age [ 33 ].…”

Section: Discussionmentioning

confidence: 99%

Yeast lifespan variation correlates with cell growth and SIR2 expression

et al. 2018

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Isogenic wild type yeast cells raised in controlled environments display a significant range of lifespan variation. Recent microfluidic studies suggest that differential growth or gene expression patterns may explain some of the heterogeneity of aging assays. Herein, we sought to complement this work by similarly examining a large set of replicative lifespan data from traditional plate assays. In so doing, we reproduced the finding that short-lived cells tend to arrest at senescence with a budded morphology. Further, we found that wild type cells born unusually small did not have an extended lifespan. However, large birth size and/or high inter-generational growth rates significantly correlated with a reduced lifespan. Finally, we found that SIR2 expression levels correlated with lifespan and intergenerational growth. SIR2 expression was significantly reduced in large cells and increased in small wild type cells. A moderate increase in SIR2 expression correlated with reduced growth, decreased proliferation and increased lifespan in plate aging assays. We conclude that cellular growth rates and SIR2 expression levels may contribute to lifespan variation in individual cells.

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“…Sir2 is one of the proteins that are abundantly expressed in long-lived yeast strains (Guo et al 2011b ). The Sir2 level decreases with replicative age, which is accompanied by an increase in H4K16ac and loss of histones at specifi c subtelomeric regions in old cells (Dang et al 2009 ).…”

Section: Sir2 In Model Organismsmentioning

confidence: 99%

The Epigenome and Aging

Kim

Jazwinski

2015

Molecular and Integrative Toxicology

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The epigenetics of aging is a relatively new fi eld. Global DNA methylation has been examined for some time; however, only recently have age-related differentially methylated regions been elaborated. These regions encompass genes that in some cases interact with longevity and disease-associated genes. Histone modifi cations have now become of interest in aging studies. Model organisms have provided substantial evidence that some of the enzymes that are involved in histone modifi cations play a role in longevity, and direct evidence of such a role for one of the sirtuins has been gathered in mice. A number of studies examining expression of microRNA during aging in various organisms, including human, point to the possibility that these gene regulatory molecules may also be involved in aging. A recent study of one such microRNA in mice substantiates such a role in cardiac aging. All of these epigenetic mechanisms are responsive to environmental and lifestyle factors. Thus, the groundwork has been laid for an understanding of the interface between the genome and the environment that epigenetic mechanisms provide.

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SIR2 and other genes are abundantly expressed in long-lived natural segregants for replicative aging of the budding yeast Saccharomyces cerevisiae

Cited by 10 publications

References 93 publications

Natural genetic variation in yeast longevity

Natural genetic variation in yeast longevity

Yeast lifespan variation correlates with cell growth and SIR2 expression

The Epigenome and Aging

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