The flavonoid 4,4’-dimethoxychalcone promotes autophagy-dependent longevity across species
Ontology highlight
ABSTRACT:
INSTRUMENT(S): LTQ Orbitrap
ORGANISM(S): Saccharomyces Cerevisiae (baker's Yeast)
SUBMITTER: 
Joern Dengjel
LAB HEAD: Joern Dengjel
PROVIDER: PXD012108 | Pride | 2019-02-22
REPOSITORIES: pride
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| 20150210_ZH_MADEO51.raw | Raw | |||
| 20150210_ZH_MADEO52.raw | Raw | |||
| 20150210_ZH_MADEO53.raw | Raw | |||
| 20150210_ZH_MADEO54.raw | Raw | |||
| 20150210_ZH_MADEO55.raw | Raw |
Items per page: 5 1 - 5 of 65 |
Publications
The flavonoid 4,4'-dimethoxychalcone promotes autophagy-dependent longevity across species.
Carmona-Gutierrez Didac D Zimmermann Andreas A Kainz Katharina K Pietrocola Federico F Chen Guo G Maglioni Silvia S Schiavi Alfonso A Nah Jihoon J Mertel Sara S Beuschel Christine B CB Castoldi Francesca F Sica Valentina V Trausinger Gert G Raml Reingard R Sommer Cornelia C Schroeder Sabrina S Hofer Sebastian J SJ Bauer Maria A MA Pendl Tobias T Tadic Jelena J Dammbrueck Christopher C Hu Zehan Z Ruckenstuhl Christoph C Eisenberg Tobias T Durand Sylvere S Bossut Noélie N Aprahamian Fanny F Abdellatif Mahmoud M Sedej Simon S Enot David P DP Wolinski Heimo H Dengjel Jörn J Kepp Oliver O Magnes Christoph C Sinner Frank F Pieber Thomas R TR Sadoshima Junichi J Ventura Natascia N Sigrist Stephan J SJ Kroemer Guido G Madeo Frank F
Nature communications 20190219 1
Ageing constitutes the most important risk factor for all major chronic ailments, including malignant, cardiovascular and neurodegenerative diseases. However, behavioural and pharmacological interventions with feasible potential to promote health upon ageing remain rare. Here we report the identification of the flavonoid 4,4'-dimethoxychalcone (DMC) as a natural compound with anti-ageing properties. External DMC administration extends the lifespan of yeast, worms and flies, decelerates senescenc ...[more]
Similar Datasets
Project description:Investigation of whole genome gene expression changes at short (2 hours) and extended (24 hours) timepoints in wild-type Saccharomyces cerevisiae treated with 50 μM menadione during exponential growth compared to an rph1Δ strain Transient treatment with 50 μM menadione elevates mitochondrial ROS and extends chronological lifespan in yeast. Deletion of RPH1, a H3K36me3 histone demethylase, block chronological lifespan extension. This study aimed to identify Rph1p-dependent gene expression changes induced by menadione treatment that may support chronological lifespan extension. Reference: Bonawitz, N.D., Chatenay-Lapointe, M., Wearn, C.M., and Shadel, G.S. (2008). Expression of the rDNA-encoded mitochondrial protein Tar1p is stringently controlled and responds differentially to mitochondrial respiratory demand and dysfunction. Curr Genet 54, 83-94. A 24 chip study using total RNA recovered from two separate cultures each of Saccharomyces cerevisiae wild-type DBY2006 and rph1Δ. Each chip measures expression levels of 5,777 transcripts from NCBI build June 2008 with 8 probes per transcript and 3 replicate probe sets.
2013-03-22 | E-GEOD-45383 | biostudies-arrayexpress
Project description:Current therapies for Fabry disease are based on reversing intra-cellular accumulation of globotriaosylceramide (Gb3) by enzyme replacement (ERT) or chaperone mediated stabilization, thereby alleviating lysosome dysfunction. However, the therapeutic effect in the regression of end-organ damage (ie. kidney damage) is limited. Ultrastructural analysis of serial human kidney biopsies showed that long-term use of ERT reduced Gb3 accumulation in podocytes but did not alter podocyte injury. A novel CRISPR-/CAS9-mediated -Galactosidase knockout podocyte cell line confirmed ERT-mediated reversal of Gb3 accumulation without resolution of lysosomal dysfunction. Transcriptomic-based connectivity mapping and SILAC-based quantitative proteomics identified alpha-synuclein (SNCA) accumulation as a key event mediating podocyte injury.
2023-07-20 | PXD029618 | Pride
Project description:Dietary restriction (DR) has been shown to increase lifespan in organisms ranging from yeast to mammals. This suggests that the underlying mechanisms may be evolutionarily conserved. Indeed, upstream signalling pathways, such as TOR, are strongly linked to DR-induced longevity in various organisms. However, the downstream effector proteins that ultimately mediate lifespan extension are less clear. To shed light on this, we used a proteomic approach on budding yeast. Our reasoning was that analysis of proteome-wide changes in response to DR might enable the identification of proteins that mediate its physiological effects, including lifespan extension. Of over 2500 proteins we identified by liquid chromatography-mass spectrometry, 183 were significantly altered in expression by at least 3-fold in response to DR. Most of these proteins were mitochondrial and/or had clear links to respiration and metabolism. Indeed, direct analysis of oxygen consumption confirmed that mitochondrial respiration was increased several-fold in response to DR. In addition, several key proteins involved in mating, including Ste2 and Ste6, were downregulated by DR. Consistent with this, shmoo formation in response to α-factor pheromone was reduced by DR, thus confirming the inhibitory effect of DR on yeast mating. Finally, we found that Hsp26, a member of the conserved small heat shock protein (sHSP) family, was upregulated by DR and that overexpression of Hsp26 extends yeast replicative lifespan. As overexpression of sHSPs in C. elegans and Drosophila has previously been shown to extend lifespan, our data on yeast Hsp26 suggest that sHSPs may be universally conserved effectors of longevity.
2022-02-17 | PXD025004 | Pride
Project description:Caloric restriction (CR) is the only non-genetic intervention to retard aging and increase longevity in a variety of species. It is important to understand the fundamental mechanism by which CR extends lifespan that remains elusive. Owing to well-established genomic tools and convenience of culture system, we used a single cell organism, Saccharomyces cerevisiae, to clarify the mechanisms of CR. In order to identify genes responsible for CR-mediated longevity, we performed microarray experiments across the longevity assurance time-points. Since the CR-treated cells obtained the longevity potential around 12 hours after inoculation and the strength of potential gradually increased up to 48 hours, we concluded that the changes across these time-points must be a critical need for assurance of longevity by CR. For preparation of total RNA, yeast cells under control (2% glucose) and CR (0.5% glucose) conditions were harvested at 12h, 18h, 24h and 48h after inoculation. After total RNA extraction, we performed Affymetrix Yeast GeneChip 2.0 array for biological triplicate repeats according to the manufacturer's instructions.
2013-12-31 | E-GEOD-41860 | biostudies-arrayexpress
Project description:Dietary amino acids restriction extends lifespan in diverse species ranging from flies to mammals. The evolutionarily conserved serine/threonine kinase General Control Nonderepressible 2 (GCN2) is a key sensor of amino acid deficiency and has been implicated in lifespan regulation upon dietary restriction. However, the role of individual essential amino acids (EAA) in modulating organismal lifespan and the underlying molecular mechanisms through which EAA mediate these effects are only partially understood. We generated a novel Drosophila GCN2 null mutant and systematically analyzed its response to individual amino acid deficiency.
2022-06-03 | GSE203210 | GEO
Project description:Cholesterol has attracted significant attention as a possible lifespan regulator. It has been reported that serum cholesterol levels have an impact on mortality due to age-related disorders such as cardiovascular disease. Diet is also known to be an important lifespan regulator. Dietary restriction retards the onset of age-related diseases and extends lifespan in various organisms. Although cholesterol and dietary restriction are known to be lifespan regulators, it remains to be established whether cholesterol is involved in dietary restriction-induced longevity. Here, we show that cholesterol deprivation suppresses longevity induced by intermittent fasting, which is one of the dietary restriction regimens that effectively extend lifespan. We also found that cholesterol is required for the fasting-induced upregulation of transcriptional target genes such as the insulin/IGF-1 pathway effector DAF-16 and that cholesterol deprivation suppresses the long lifespan of the insulin/IGF-1 receptor daf-2 mutant. Remarkably, we found that cholesterol plays an important role in the fasting-induced nuclear accumulation of DAF-16. Moreover, knockdown of the cholesterol-binding protein NSBP-1, which has been shown to bind to DAF-16 in a cholesterol-dependent manner and to regulate DAF-16 activity, suppresses both fasting-induced longevity and DAF-16 nuclear accumulation. Furthermore, this suppression was not additive to the cholesterol deprivation-induced suppression, which suggests that NSBP-1 mediates, at least in part, the action of cholesterol to promote fasting-induced longevity and DAF-16 nuclear accumulation. These findings identify a novel role for cholesterol in the regulation of lifespan. Two independent replicates were performed. Total RNA was extracted with TRIzol (Invitrogen). The extracted RNA was purified with PureLink RNA Micro Kit (Invitrogen) and analyzed with Agilent 2100 Bioanalyzer to assess the RNA integrity. The microarray procedures were performed according to Affymetrix protocols. Hybridized arrays were scanned using an Affymetrix GeneChip Scanner.
2017-05-01 | E-GEOD-51046 | biostudies-arrayexpress
Project description:Tardigrades are remarkable in their ability to survive extreme environments. The damage suppressor (Dsup) protein is thought responsible for their extreme resistance to reactive oxygen species (ROS) generated by irradiation. Here we show that expression of Ramazzottius varieornatus Dsup in Saccharomyces cerevisiae reduces oxidative DNA damage and extends the lifespan of budding yeast with chronic oxidative damage. This protection from ROS requires either the Dsup HMGN-like domain or sequences C-terminal to same. Dsup associates with no apparent bias across the yeast genome, using multiple modes of nucleosome binding; the HMGN-like region interacts with both the H2A/H2B acidic patch and H3/H4 histone tails, while the C-terminal region binds DNA. These findings give precedent for engineering an organism by physically shielding its genome to promote survival and longevity in the face of oxidative damage.
2024-01-14 | GSE237436 | GEO
Project description:mTORC1 (mechanistic target of rapamycin complex 1) is a metabolic sensor that promotes growth when nutrients are abundant. Ubiquitous inhibition of mTORC1 extends lifespan in multiple organisms but also disrupts several anabolic processes resulting in stunted growth, slowed development, reduced fertility, and disrupted metabolism. However, it is unclear if these pleotropic effects of mTORC1 inhibition can be uncoupled from longevity. Here, we utilize the auxin-inducible degradation (AID) system to restrict mTORC1 inhibition to C. elegans neurons. We find that neuron-specific degradation of RAGA-1, an upstream activator of mTORC1, or LET-363, the ortholog of mammalian mTOR, is sufficient to extend lifespan in C. elegans. Unlike raga-1 loss of function genetic mutations or somatic AID of RAGA-1, neuronal AID of RAGA-1 robustly extends lifespan without impairing body size, developmental rate, brood size or neuronal function. Moreover, while somatic degradation of RAGA-1 alters the expression of thousands of genes, demonstrating the widespread effects of mTORC1 inhibition, neuronal degradation of RAGA-1 only results in around 200 differentially expressed genes with a specific enrichment in metabolism and stress response. Notably, our work demonstrates that targeting mTORC1 specifically in the nervous system in C. elegans uncouples longevity from growth and reproductive impairments, and that many canonical effects of low mTORC1 activity are not required to promote healthy aging. These data challenge previously held ideas about the mechanisms of mTORC1 lifespan extension and underscore the potential of promoting longevity by neuron-specific mTORC1 modulation.
2023-07-18 | GSE237060 | GEO
Project description:Epigenetic mechanisms including histone post-translational modifications control longevity in diverse organisms. Relatedly, loss of proper transcriptional regulation on a global scale is an emerging aspect of shortened lifespan, but the specific mechanisms linking these observations remain to be uncovered. Here, we describe a lifespan screen in S. cerevisiae, designed to identify altered amino acid residues of histones that alter yeast replicative aging. Our results reveal that lack of sustained H3K36 methylation is commensurate with increased cryptic transcription in a set of genes in old cells and shorter lifespan. Deletion of the K36me2/3 demethylase Rph1 increases H3K36me3 within these genes and suppresses cryptic transcript initiation to extend lifespan. We show that this aging phenomenon is conserved, as cryptic transcription also increases in old worms. We propose that epigenetic misregulation in aging cells leads to an increase in transcriptional noise that is detrimental to lifespan, and, importantly, this acceleration in aging can be reversed by restoring transcriptional fidelity.
2015-07-17 | GSE65766 | GEO
Project description:Caloric restriction and intermittent fasting prolong the lifespan and healthspan of model organisms and improve human health 1. The natural polyamine spermidine has been linked to autophagy regulation, geroprotection and reduced incidence of cardiovascular and neurodegenerative diseases across species borders 2. Here, we report that spermidine levels increase upon acute fasting in yeast, flies, mice and healthy humans. Genetic or pharmacological blockade of endogenous spermidine synthesis reduced fasting-induced autophagy in yeast, worms and human cells. Furthermore, perturbing the polyamine pathway in vivo abrogated the lifespan-extending, cardioprotective and antiarthritic effects of intermittent fasting. Mechanistically, spermidine mediated these effects via hypusination of the autophagy regulator eIF5A. In sum, the polyamine-hypusination axis thus emerges as a bona fide and phylogenetically conserved metabolic control hub for longevity and autophagy induction.
2024-04-30 | PXD035909 | Pride