Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

An Energy-Independent Pro-longevity Function of Triacylglycerol in Yeast.

ABSTRACT: Intracellular triacylglycerol (TAG) is a ubiquitous energy storage lipid also involved in lipid homeostasis and signaling. Comparatively, little is known about TAG's role in other cellular functions. Here we show a pro-longevity function of TAG in the budding yeast Saccharomyces cerevisiae. In yeast strains derived from natural and laboratory environments a correlation between high levels of TAG and longer chronological lifespan was observed. Increased TAG abundance through the deletion of TAG lipases prolonged chronological lifespan of laboratory strains, while diminishing TAG biosynthesis shortened lifespan without apparently affecting vegetative growth. TAG-mediated lifespan extension was independent of several other known stress response factors involved in chronological aging. Because both lifespan regulation and TAG metabolism are conserved, this cellular pro-longevity function of TAG may extend to other organisms.

SUBMITTER: Handee W

PROVIDER: S-EPMC4764362 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

An Energy-Independent Pro-longevity Function of Triacylglycerol in Yeast.

Handee Witawas W Li Xiaobo X Hall Kevin W KW Deng Xiexiong X Li Pan P Benning Christoph C Williams Barry L BL Kuo Min-Hao MH

PLoS genetics 20160223 2

Intracellular triacylglycerol (TAG) is a ubiquitous energy storage lipid also involved in lipid homeostasis and signaling. Comparatively, little is known about TAG's role in other cellular functions. Here we show a pro-longevity function of TAG in the budding yeast Saccharomyces cerevisiae. In yeast strains derived from natural and laboratory environments a correlation between high levels of TAG and longer chronological lifespan was observed. Increased TAG abundance through the deletion of TAG l ...[more]

PMID: 26907989

Similar Datasets

Independent and additive effects of glutamic acid and methionine on yeast longevity.

Project description:It is established that glucose restriction extends yeast chronological and replicative lifespan, but little is known about the influence of amino acids on yeast lifespan, although some amino acids were reported to delay aging in rodents. Here we show that amino acid composition greatly alters yeast chronological lifespan. We found that non-essential amino acids (to yeast) methionine and glutamic acid had the most significant impact on yeast chronological lifespan extension, restriction of methionine and/or increase of glutamic acid led to longevity that was not the result of low acetic acid production and acidification in aging media. Remarkably, low methionine, high glutamic acid and glucose restriction additively and independently extended yeast lifespan, which could not be further extended by buffering the medium (pH 6.0). Our preliminary findings using yeasts with gene deletion demonstrate that glutamic acid addition, methionine and glucose restriction prompt yeast longevity through distinct mechanisms. This study may help to fill a gap in yeast model for the fast developing view that nutrient balance is a critical factor to extend lifespan.

| S-EPMC3820698 | biostudies-literature

Sir2 and Glycerol Underlie the Pro-Longevity Effect of Quercetin during Yeast Chronological Aging.

Project description:Quercetin (QUER) is a natural polyphenolic compound endowed with beneficial properties for human health, with anti-aging effects. However, although this flavonoid is commercially available as a nutraceutical, target molecules/pathways underlying its pro-longevity potential have yet to be fully clarified. Here, we investigated QUER activity in yeast chronological aging, the established model for simulating the aging of postmitotic quiescent mammalian cells. We found that QUER supplementation at the onset of chronological aging, namely at the diauxic shift, significantly increases chronological lifespan (CLS). Consistent with the antioxidant properties of QUER, this extension takes place in concert with a decrease in oxidative stress. In addition, QUER triggers substantial changes in carbon metabolism. Specifically, it promotes an enhancement of a pro-longevity anabolic metabolism toward gluconeogenesis due to improved catabolism of C2 by-products of yeast fermentation and glycerol. The former is attributable to the Sir2-dependent activity of phosphoenolpyruvate carboxykinase and the latter to the L-glycerol 3-phosphate pathway. Such a combined increased supply of gluconeogenesis leads to an increase in the reserve carbohydrate trehalose, ensuring CLS extension. Moreover, QUER supplementation to chronologically aging cells in water alone amplifies their long-lived phenotype. This is associated with intracellular glycerol catabolism and trehalose increase, further indicating a QUER-specific influence on carbon metabolism that results in CLS extension.

| S-EPMC10419316 | biostudies-literature

Replication-Independent Histone Variant H3.3 Controls Animal Lifespan through the Regulation of Pro-longevity Transcriptional Programs.

Project description:Chromatin structure orchestrates the accessibility to the genetic material. Replication-independent histone variants control transcriptional plasticity in postmitotic cells. The life-long accumulation of these histones has been described, yet the implications on organismal aging remain elusive. Here, we study the importance of the histone variant H3.3 in Caenorhabditis elegans longevity pathways. We show that H3.3-deficient nematodes have negligible lifespan differences compared to wild-type animals. However, H3.3 is essential for the lifespan extension of C. elegans mutants in which pronounced transcriptional changes control longevity programs. Notably, H3.3 loss critically affects the expression of a very large number of genes in long-lived nematodes, resulting in transcriptional profiles similar to wild-type animals. We conclude that H3.3 positively contributes to diverse lifespan-extending signaling pathways, with potential implications on age-related processes in multicellular organisms.

| S-EPMC5081402 | biostudies-literature

Triacylglycerol synthesis enhances macrophage inflammatory function

Project description:Macrophages stimulated with lipopolysaccharide (LPS) plus interferon-g (IFNg) accumulate TGs in LDs, and long-chain acylcarnitines. Inhibition of TG synthesis results in diminished LD development, and increased long chain acylcarnitine levels, suggesting that FA fate is balanced between TG and acylcarnitine synthesis. Nevertheless, TG-synthesis is required for inflammatory macrophage function, since its inhibition negatively affects production of proinflammatory IL-1b, IL-6 and PGE2, and phagocytic capacity, and protects against LPS-induced sock in vivo.

2020-07-04 | GSE145523 | GEO

Characterization of the putative yeast mitochondrial triacylglycerol lipase Tgl2.

Project description:Mitochondria derive the majority of their lipids from other organelles through contact sites. These lipids, primarily phosphoglycerolipids, are the main components of mitochondrial membranes. In the cell, neutral lipids like triacylglycerides (TAGs) are stored in lipid droplets, playing an important role in maintaining cellular health. Enzymes like lipases mobilize these TAGs according to cellular needs. Neutral lipids have not yet been reported to play an important role in mitochondria so the presence of a putative TAG lipase-Tgl2, in yeast mitochondria is surprising. Moreover, TGL2 and MCP2, a high-copy suppressor for ER mitochondria encounter structure deficient cells, display genetic interactions suggesting a potential link of both proteins to lipid metabolism. In this study, we characterize in detail Tgl2. We show that Tgl2 forms dimers through intermolecular disulfide bridges and a cysteine-dependent high molecular weight complex. Furthermore, we could identify the lipase motif and catalytic triad of Tgl2 through in silico comparison with other lipases. Mutating each of the three catalytically active residues resulted in variants that failed to rescue the growth phenotype of mcp2Δ tgl2Δ double deletion strain supporting the assumption that these residues are indeed essential for the protein's function. Additionally, we discovered that the catalytically active aspartate residue (D259) is important for protein stability. Steady state level analyses with unstable variants of Tgl2 led to the identification of Yme1 as the protease responsible for its quality control. Finally, we provide evidence that the overall increase in TAGs in cells lacking Mcp2 and Tgl2 originates from the mitochondria. Collectively, our study provides new insights into a key player in mitochondrial lipid homeostasis.

| S-EPMC11889585 | biostudies-literature

Triacylglycerol synthesis enhances macrophage inflammatory function.

Project description:Foamy macrophages, which have prominent lipid droplets (LDs), are found in a variety of disease states. Toll-like receptor agonists drive triacylglycerol (TG)-rich LD development in macrophages. Here we explore the basis and significance of this process. Our findings indicate that LD development is the result of metabolic commitment to TG synthesis on a background of decreased fatty acid oxidation. TG synthesis is essential for optimal inflammatory macrophage activation as its inhibition, which prevents LD development, has marked effects on the production of inflammatory mediators, including IL-1β, IL-6 and PGE2, and on phagocytic capacity. The failure of inflammatory macrophages to make PGE2 when TG-synthesis is inhibited is critical for this phenotype, as addition of exogenous PGE2 is able to reverse the anti-inflammatory effects of TG synthesis inhibition. These findings place LDs in a position of central importance in inflammatory macrophage activation.

| S-EPMC7427976 | biostudies-literature

A pro longevity role for cellular senescence.

Project description:Cellular senescence is a fundamental process that may play positive or detrimental roles for the organism. It is involved in tissue development and in tumor prevention although during aging is becoming a detrimental process contributing to the decline of tissue functions. In previous investigations, we have uncovered a better capacity to detect DNA damage in cells from long-lived mammals. Here, we report that cultured cells derived from long-lived species have a higher propensity to undergo senescence when challenged with DNA damage than cells derived from short-lived species. Using a panel of cells derived from six mammals, which range in lifespan from 3-4 years up to 120 years, we examined cell cycle response, induction of apoptosis and of cellular senescence. All species exhibited a cell cycle arrest while induction of apoptosis was variable. However, a significant positive correlation was found between the relative percent of cells, within a population which entered senescence following damage, and the lifespan of the species. We suggest that cellular senescence may have a positive role during development allowing it to contribute to the evolution of longevity.

| S-EPMC7286999 | biostudies-literature

Conservation of pro-longevity genes among mammals.

Project description:Genes which confer a relative longevity advantage may be regulated at the level of transcription or translation. Alternatively, pro-longevity genes may mediate their effects at the level of protein structure-functional relationships that are beneficially optimized in long-lived species. Longevity associated genes (LAGs) may be operationally defined as genes that confer beneficial effects and are relatively more conserved among long-lived species. Global and local protein sequence alignments of over 10,000 genes across at least 30 mammalian species were examined to identify LAGs. Known LAGs, including growth hormone receptor (GHR), and breast cancer 1, early onset (BRCA1), have strong associations with maximum lifespan by our analysis. Several common categories of protein function were observed among genes ranked with the strongest associations with MLS identified by all regression models. These genes included those that function in the immune system, cell cycle regulation, and DNA damage response. We provide a ranking of genes with the strongest associations with species maximum lifespan (MLS) by several phylogenetic generalized least squares regression models, including adjustment for confounding variables such as body weight and gestation length.

| S-EPMC4457664 | biostudies-literature

Mitochondrial membrane lipidome defines yeast longevity.

Project description:Our studies revealed that lithocholic acid (LCA), a bile acid, is a potent anti-aging natural compound that in yeast cultured under longevity-extending caloric restriction (CR) conditions acts in synergy with CR to enable a significant further increase in chronological lifespan. Here, we investigate a mechanism underlying this robust longevity-extending effect of LCA under CR. We found that exogenously added LCA enters yeast cells, is sorted to mitochondria, resides mainly in the inner mitochondrial membrane, and also associates with the outer mitochondrial membrane. LCA elicits an age-related remodeling of glycerophospholipid synthesis and movement within both mitochondrial membranes, thereby causing substantial changes in mitochondrial membrane lipidome and triggering major changes in mitochondrial size, number and morphology. In synergy, these changes in the membrane lipidome and morphology of mitochondria alter the age-related chronology of mitochondrial respiration, membrane potential, ATP synthesis and reactive oxygen species homeostasis. The LCA-driven alterations in the age-related dynamics of these vital mitochondrial processes extend yeast longevity. In sum, our findings suggest a mechanism underlying the ability of LCA to delay chronological aging in yeast by accumulating in both mitochondrial membranes and altering their glycerophospholipid compositions. We concluded that mitochondrial membrane lipidome plays an essential role in defining yeast longevity.

| S-EPMC3765583 | biostudies-literature

Natural genetic variation in yeast longevity.

Project description: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.

| S-EPMC3460191 | 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