Browse
Submit Data
Databases
API
Help

Dataset Information

25 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Screening of selected ageing-related proteins that extend chronological life span in yeast Saccharomyces cerevisiae.

ABSTRACT: Ageing-related proteins play various roles such as regulating cellular ageing, countering oxidative stress, and modulating signal transduction pathways amongst many others. Hundreds of ageing-related proteins have been identified, however the functions of most of these ageing-related proteins are not known. Here, we report the identification of proteins that extended yeast chronological life span (CLS) from a screen of ageing-related proteins. Three of the CLS-extending proteins, Ptc4, Zwf1, and Sme1, contributed to an overall higher survival percentage and shorter doubling time of yeast growth compared to the control. The CLS-extending proteins contributed to thermal and oxidative stress responses differently, suggesting different mechanisms of actions. The overexpression of Ptc4 or Zwf1 also promoted rapid cell proliferation during yeast growth, suggesting their involvement in cell division or growth pathways.

SUBMITTER: Lee JW

PROVIDER: S-EPMC8683414 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Dietary restriction depends on nutrient composition to extend chronological lifespan in budding yeast Saccharomyces cerevisiae.

Project description:The traditional view on dietary restriction has been challenged with regard to extending lifespan of the fruit fly Drosophila melanogaster. This is because studies have shown that changing the balance of dietary components without reduction of dietary intake can increase lifespan, suggesting that nutrient composition other than dietary restriction play a pivotal role in regulation of longevity. However, this opinion has not been reflected in yeast aging studies. Inspired by this new finding, response surface methodology was applied to evaluate the relationships between nutrients (glucose, amino acids and yeast nitrogen base) and lifespan as well as biomass production in four Saccharomyces cerevisiae strains (wild-type BY4742, sch9?, tor1?, and sir2? mutants) using a high throughput screening assay. Our results indicate that lifespan extension by a typical dietary restriction regime was dependent on the nutrients in media and that nutrient composition was a key determinant for yeast longevity. Four different yeast strains were cultured in various media, which showed similar response surface trends in biomass production and viability at day two but greatly different trends in lifespan. The pH of aging media was dependent on glucose concentration and had no apparent correlation with lifespan under conditions where amino acids and YNB were varied widely, and simply buffering the pH of media could extend lifespan significantly. Furthermore, the results showed that strain sch9? was more responsive in nutrient-sensing than the other three strains, suggesting that Sch9 (serine-threonine kinase pathway) was a major nutrient-sensing factor that regulates cell growth, cell size, metabolism, stress resistance and longevity. Overall, our findings support the notion that nutrient composition might be a more effective way than simple dietary restriction to optimize lifespan and biomass production from yeast to other organisms.

| S-EPMC3656888 | biostudies-literature

Transcriptomic analysis of a Saccharomyces cerevisiae mutant with extended chronological life span

Project description:A Saccharomyces cerevisiae mutant with extended chronological life span was obtained by using an evolutionary engineering strategy, based on successive batch cultivation under gradually enhanced caloric restriction. The mutant strain SRM11 was selected which had about 50% longer life span than the reference strain. Whole-genome transcriptomic analysis of SRM11 with respect to the reference strain was performed to identify differences in gene expression levels between the two strains.

2017-05-19 | GSE99041 | GEO

Natural variation of chronological aging in the Saccharomyces cerevisiae species reveals diet-dependent mechanisms of life span control.

Project description:Aging is a complex trait of broad scientific interest, especially because of its intrinsic link with common human diseases. Pioneering work on aging-related mechanisms has been made in Saccharomyces cerevisiae, mainly through the use of deletion collections isogenic to the S288c reference strain. In this study, using a recently published high-throughput approach, we quantified chronological life span (CLS) within a collection of 58 natural strains across seven different conditions. We observed a broad aging variability suggesting the implication of diverse genetic and environmental factors in chronological aging control. Two major Quantitative Trait Loci (QTLs) were identified within a biparental population obtained by crossing two natural isolates with contrasting aging behavior. Detection of these QTLs was dependent upon the nature and concentration of the carbon sources available for growth. In the first QTL, the RIM15 gene was identified as major regulator of aging under low glucose condition, lending further support to the importance of nutrient-sensing pathways in longevity control under calorie restriction. In the second QTL, we could show that the SER1 gene, encoding a conserved aminotransferase of the serine synthesis pathway not previously linked to aging, is causally associated with CLS regulation, especially under high glucose condition. These findings hint toward a new mechanism of life span control involving a trade-off between serine synthesis and aging, most likely through modulation of acetate and trehalose metabolism. More generally it shows that genetic linkage studies across natural strains represent a promising strategy to further unravel the molecular basis of aging.

| S-EPMC5845861 | biostudies-literature

The Stationary-Phase Cells of Saccharomyces cerevisiae Display Dynamic Actin Filaments Required for Processes Extending Chronological Life Span.

Project description:Stationary-growth-phase Saccharomyces cerevisiae yeast cultures consist of nondividing cells that undergo chronological aging. For their successful survival, the turnover of proteins and organelles, ensured by autophagy and the activation of mitochondria, is performed. Some of these processes are engaged in by the actin cytoskeleton. In S. cerevisiae stationary-phase cells, F actin has been shown to form static aggregates named actin bodies, subsequently cited to be markers of quiescence. Our in vivo analyses revealed that stationary-phase cultures contain cells with dynamic actin filaments, besides the cells with static actin bodies. The cells with dynamic actin displayed active endocytosis and autophagy and well-developed mitochondrial networks. Even more, stationary-phase cell cultures grown under calorie restriction predominantly contained cells with actin cables, confirming that the presence of actin cables is linked to successful adaptation to stationary phase. Cells with actin bodies were inactive in endocytosis and autophagy and displayed aberrations in mitochondrial networks. Notably, cells of the respiratory activity-deficient cox4? strain displayed the same mitochondrial aberrations and actin bodies only. Additionally, our results indicate that mitochondrial dysfunction precedes the formation of actin bodies and the appearance of actin bodies corresponds to decreased cell fitness. We conclude that the F-actin status reflects the extent of damage that arises from exponential growth.

| S-EPMC4609741 | biostudies-literature

Oxidative stress tolerance, adenylate cyclase, and autophagy are key players in the chronological life span of Saccharomyces cerevisiae during winemaking.

Project description:Most grape juice fermentation takes place when yeast cells are in a nondividing state called the stationary phase. Under such circumstances, we aimed to identify the genetic determinants controlling longevity, known as the chronological life span. We identified commercial strains with both short (EC1118) and long (CSM) life spans in laboratory growth medium and compared them under diverse conditions. Strain CSM shows better tolerance to stresses, including oxidative stress, in the stationary phase. This is reflected during winemaking, when this strain has an increased maximum life span. Compared to EC1118, CSM overexpresses a mitochondrial rhodanese gene-like gene, RDL2, whose deletion leads to increased reactive oxygen species production at the end of fermentation and a correlative loss of viability at this point. EC1118 shows faster growth and higher expression of glycolytic genes, and this is related to greater PKA activity due to the upregulation of the adenylate cyclase gene. This phenotype has been linked to the presence of a ? element in its promoter, whose removal increases the life span. Finally, EC1118 exhibits a higher level of protein degradation by autophagy, which might help achieve fast growth at the expense of cellular structures and may be relevant for long-term survival under winemaking conditions.

| S-EPMC3318821 | biostudies-literature

Regulation of yeast chronological life span by TORC1 via adaptive mitochondrial ROS signaling.

Project description:Here we show that yeast strains with reduced target of rapamycin (TOR) signaling have greater overall mitochondrial electron transport chain activity during growth that is efficiently coupled to ATP production. This metabolic alteration increases mitochondrial membrane potential and reactive oxygen species (ROS) production, which we propose supplies an adaptive signal during growth that extends chronological life span (CLS). In strong support of this concept, uncoupling respiration during growth or increasing expression of mitochondrial manganese superoxide dismutase significantly curtails CLS extension in tor1? strains, and treatment of wild-type strains with either rapamycin (to inhibit TORC1) or menadione (to generate mitochondrial ROS) during growth is sufficient to extend CLS. Finally, extension of CLS by reduced TORC1/Sch9p-mitochondrial signaling occurs independently of Rim15p and is not a function of changes in media acidification/composition. Considering the conservation of TOR-pathway effects on life span, mitochondrial ROS signaling may be an important mechanism of longevity regulation in higher organisms.

| S-EPMC3110654 | biostudies-literature

Mitochondrial dysfunction increases oxidative stress and decreases chronological life span in fission yeast.

Project description:BackgroundOxidative stress is a probable cause of aging and associated diseases. Reactive oxygen species (ROS) originate mainly from endogenous sources, namely the mitochondria.Methodology/principal findingsWe analyzed the effect of aerobic metabolism on oxidative damage in Schizosaccharomyces pombe by global mapping of those genes that are required for growth on both respiratory-proficient media and hydrogen-peroxide-containing fermentable media. Out of a collection of approximately 2700 haploid yeast deletion mutants, 51 were sensitive to both conditions and 19 of these were related to mitochondrial function. Twelve deletion mutants lacked components of the electron transport chain. The growth defects of these mutants can be alleviated by the addition of antioxidants, which points to intrinsic oxidative stress as the origin of the phenotypes observed. These respiration-deficient mutants display elevated steady-state levels of ROS, probably due to enhanced electron leakage from their defective transport chains, which compromises the viability of chronologically-aged cells.Conclusion/significanceIndividual mitochondrial dysfunctions have often been described as the cause of diseases or aging, and our global characterization emphasizes the primacy of oxidative stress in the etiology of such processes.

| S-EPMC2475502 | biostudies-literature

Mitochondrial respiratory thresholds regulate yeast chronological life span and its extension by caloric restriction.

Project description:We have explored the role of mitochondrial function in aging by genetically and pharmacologically modifying yeast cellular respiration production during the exponential and/or stationary growth phases and determining how this affects chronological life span (CLS). Our results demonstrate that respiration is essential during both growth phases for standard CLS, but that yeast have a large respiratory capacity, and only deficiencies below a threshold (~40% of wild-type) significantly curtail CLS. Extension of CLS by caloric restriction also required respiration above a similar threshold during exponential growth and completely alleviated the need for respiration in the stationary phase. Finally, we show that supplementation of media with 1% trehalose, a storage carbohydrate, restores wild-type CLS to respiratory-null cells. We conclude that mitochondrial respiratory thresholds regulate yeast CLS and its extension by caloric restriction by increasing stress resistance, an important component of which is the optimal accumulation and mobilization of nutrient stores.

| S-EPMC3397320 | biostudies-literature

Genomic instability is associated with natural life span variation in Saccharomyces cerevisiae.

Project description:Increasing genomic instability is associated with aging in eukaryotes, but the connection between genomic instability and natural variation in life span is unknown. We have quantified chronological life span and loss-of-heterozygosity (LOH) in 11 natural isolates of Saccharomyces cerevisiae. We show that genomic instability increases and mitotic asymmetry breaks down during chronological aging. The age-dependent increase of genomic instability generally lags behind the drop of viability and this delay accounts for approximately 50% of the observed natural variation of replicative life span in these yeast isolates. We conclude that the abilities of yeast strains to tolerate genomic instability co-vary with their replicative life spans. To the best of our knowledge, this is the first quantitative evidence that demonstrates a link between genomic instability and natural variation in life span.

| S-EPMC2441830 | biostudies-literature

Project description:Sphingoid bases (SBs) as bioactive sphingolipids, have been implicated in aging in yeast. However, we know neither how SBs are regulated during yeast aging nor how they, in turn, regulate it. Herein, we demonstrate that the yeast alkaline ceramidases (YPC1 and YDC1) and SB kinases (LCB4 and LCB5) cooperate in regulating SBs during the aging process and that SBs shortens chronological life span (CLS) by compromising mitochondrial functions. With a lipidomics approach, we found that SBs were increased in a time-dependent manner during yeast aging. We also demonstrated that among the enzymes known for being responsible for the metabolism of SBs, YPC1 was upregulated whereas LCB4/5 were downregulated in the course of aging. This inverse regulation of YPC1 and LCB4/5 led to the aging-related upregulation of SBs in yeast and a reduction in CLS. With the proteomics-based approach (SILAC), we revealed that increased SBs altered the levels of proteins related to mitochondria. Further mechanistic studies demonstrated that increased SBs inhibited mitochondrial fusion and caused fragmentation, resulting in decreases in mtDNA copy numbers, ATP levels, mitochondrial membrane potentials, and oxygen consumption. Taken together, these results suggest that increased SBs mediate the aging process by impairing mitochondrial structural integrity and functions.

| S-EPMC5008273 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data