LIVIVO - Search results -

Search results

Result 1 - 10 of total 13

Search options

Article ; Online: Mitochondrial cross-compartmental signalling to maintain proteostasis and longevity.

Molenaars, Marte / Daniels, Eileen G / Meurs, Amber / Janssens, Georges E / Houtkooper, Riekelt H

Philosophical transactions of the Royal Society of London. Series B, Biological sciences

2020 Volume 375, Issue 1801, Page(s) 20190414

Abstract: Lifespan in eukaryotic species can be prolonged by shifting from cellular states favouring growth to those favouring maintenance and stress resistance. For instance, perturbations in mitochondrial oxidative phosphorylation (OXPHOS) can shift cells into ... ...

Abstract	Lifespan in eukaryotic species can be prolonged by shifting from cellular states favouring growth to those favouring maintenance and stress resistance. For instance, perturbations in mitochondrial oxidative phosphorylation (OXPHOS) can shift cells into this latter state and extend lifespan. Because mitochondria rely on proteins synthesized from nuclear as well as mitochondrial DNA, they need to constantly send and receive messages from other compartments of the cell in order to function properly and maintain homeostasis, and lifespan extension is often dependent on this cross-compartmental signalling. Here, we describe the mechanisms of bi-directional mitochondrial cross-compartmental signalling resulting in proteostasis and longevity. These proteostasis mechanisms are highly context-dependent, governed by the origin and extent of stress. Furthermore, we discuss the translatability of these mechanisms and explore therapeutic developments, such as the antibiotic studies targeting mitochondria or mitochondria-derived peptides as therapies for age-related diseases such as neurodegeneration and cancer. This article is part of the theme issue 'Retrograde signalling from endosymbiotic organelles'.
MeSH term(s)	Humans ; Longevity ; Mitochondria/physiology ; Neoplasms/therapy ; Neurodegenerative Diseases/therapy ; Proteostasis ; Signal Transduction
Language	English
Publishing date	2020-05-04
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	208382-6
ISSN	1471-2970 ; 0080-4622 ; 0264-3839 ; 0962-8436
ISSN (online)	1471-2970
ISSN	0080-4622 ; 0264-3839 ; 0962-8436
DOI	10.1098/rstb.2019.0414
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Einzelsignatur: Show issues

Order via subito

This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: From molecular promise to preclinical results: HDAC inhibitors in the race for healthy aging drugs.

McIntyre, Rebecca L / Daniels, Eileen G / Molenaars, Marte / Houtkooper, Riekelt H / Janssens, Georges E

EMBO molecular medicine

2019 Volume 11, Issue 9, Page(s) e9854

Abstract: Reversing or slowing the aging process brings great promise to treat or prevent age-related disease, and targeting the hallmarks of aging is a strategy to achieve this. Epigenetics affects several if not all of the hallmarks of aging and has therefore ... ...

Abstract	Reversing or slowing the aging process brings great promise to treat or prevent age-related disease, and targeting the hallmarks of aging is a strategy to achieve this. Epigenetics affects several if not all of the hallmarks of aging and has therefore emerged as a central target for intervention. One component of epigenetic regulation involves histone deacetylases (HDAC), which include the "classical" histone deacetylases (of class I, II, and IV) and sirtuin deacetylases (of class III). While targeting sirtuins for healthy aging has been extensively reviewed elsewhere, this review focuses on pharmacologically inhibiting the classical HDACs to promote health and longevity. We describe the theories of how classical HDAC inhibitors may operate to increase lifespan, supported by studies in model organisms. Furthermore, we explore potential mechanisms of how HDAC inhibitors may have such a strong grasp on health and longevity, summarizing their links to other hallmarks of aging. Finally, we show the wide range of age-related preclinical disease models, ranging from neurodegeneration to heart disease, diabetes to sarcopenia, which show improvement upon HDAC inhibition.
MeSH term(s)	Animals ; Drug Evaluation, Preclinical ; Epigenesis, Genetic ; Healthy Aging/drug effects ; Healthy Aging/metabolism ; Histone Deacetylase Inhibitors/administration & dosage ; Histone Deacetylases/genetics ; Histone Deacetylases/metabolism ; Humans ; Longevity/drug effects
Chemical Substances	Histone Deacetylase Inhibitors ; Histone Deacetylases (EC 3.5.1.98)
Language	English
Publishing date	2019-08-01
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2467145-9
ISSN	1757-4684 ; 1757-4676
ISSN (online)	1757-4684
ISSN	1757-4676
DOI	10.15252/emmm.201809854
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 6784: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Anti-retroviral treatment with zidovudine alters pyrimidine metabolism, reduces translation, and extends healthy longevity via ATF-4.

McIntyre, Rebecca L / Molenaars, Marte / Schomakers, Bauke V / Gao, Arwen W / Kamble, Rashmi / Jongejan, Aldo / van Weeghel, Michel / van Kuilenburg, André B P / Possemato, Richard / Houtkooper, Riekelt H / Janssens, Georges E

Cell reports

2022 Volume 42, Issue 1, Page(s) 111928

Abstract: The human population is aging, and the need for interventions to slow progression of age-related diseases (geroprotective interventions) is growing. Repurposing compounds already used clinically, usually at modified doses, allows rapid implementation of ... ...

Abstract	The human population is aging, and the need for interventions to slow progression of age-related diseases (geroprotective interventions) is growing. Repurposing compounds already used clinically, usually at modified doses, allows rapid implementation of geroprotective pharmaceuticals. Here we find the anti-retroviral nucleoside reverse transcriptase inhibitor (NRTI) zidovudine robustly extends lifespan and health span in C. elegans, independent of electron transport chain impairment or ROS accumulation. Rather, zidovudine treatment modifies pyrimidine metabolism and transcripts related to proteostasis. Testing regulators of mitochondrial stress and proteostasis shows that lifespan extension is dependent on activating transcription factor 4 (ATF-4). ATF-4 regulates longevity induced by mitochondrial stress, specifically communication between mitochondrial and cytosolic translation. Translation is reduced in zidovudine-treated worms, also dependent on ATF-4. Finally, we show ATF-4-dependent lifespan extension induced by didanosine, another NRTI. Altogether, our work elucidates the geroprotective effects of NRTIs such as zidovudine in vivo, via reduction of translation and ATF-4.
MeSH term(s)	Animals ; Humans ; Zidovudine/pharmacology ; Zidovudine/therapeutic use ; Longevity ; Activating Transcription Factor 4 ; Caenorhabditis elegans/physiology ; Reverse Transcriptase Inhibitors/pharmacology ; Reverse Transcriptase Inhibitors/therapeutic use ; Retroviridae ; HIV Infections/drug therapy
Chemical Substances	Zidovudine (4B9XT59T7S) ; Activating Transcription Factor 4 (145891-90-3) ; Reverse Transcriptase Inhibitors
Language	English
Publishing date	2022-12-30
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2649101-1
ISSN	2211-1247 ; 2211-1247
ISSN (online)	2211-1247
ISSN	2211-1247
DOI	10.1016/j.celrep.2022.111928
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: Multi-omics analysis identifies essential regulators of mitochondrial stress response in two wild-type

Gao, Arwen W / El Alam, Gaby / Lalou, Amélia / Li, Terytty Yang / Molenaars, Marte / Zhu, Yunyun / Overmyer, Katherine A / Shishkova, Evgenia / Hof, Kevin / Bou Sleiman, Maroun / Houtkooper, Riekelt H / Coon, Joshua J / Auwerx, Johan

iScience

2022 Volume 25, Issue 2, Page(s) 103734

Abstract: The mitochondrial unfolded protein response (UPRmt) is a promising pharmacological target for aging and age-related diseases. However, the integrative analysis of the impact of UPRmt activation on different signaling layers in animals with different ... ...

Abstract	The mitochondrial unfolded protein response (UPRmt) is a promising pharmacological target for aging and age-related diseases. However, the integrative analysis of the impact of UPRmt activation on different signaling layers in animals with different genetic backgrounds is lacking. Here, we applied systems approaches to investigate the effect of UPRmt induced by doxycycline (Dox) on transcriptome, proteome, and lipidome in two genetically divergent worm strains, named N2 and CB4856. From the integrated omics datasets, we found that Dox prolongs lifespan of both worm strains through shared and strain-specific mechanisms. Specifically, Dox strongly impacts mitochondria, upregulates defense response, and lipid metabolism, while decreasing triglycerides. We further validated that lipid genes
Language	English
Publishing date	2022-01-05
Publishing country	United States
Document type	Journal Article
ISSN	2589-0042
ISSN (online)	2589-0042
DOI	10.1016/j.isci.2022.103734
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article: Integrating the Hallmarks of Aging Throughout the Tree of Life: A Focus on Mitochondrial Dysfunction.

van der Rijt, Sanne / Molenaars, Marte / McIntyre, Rebecca L / Janssens, Georges E / Houtkooper, Riekelt H

Frontiers in cell and developmental biology

2020 Volume 8, Page(s) 594416

Abstract: Since the identification and definition of the hallmarks of aging, these aspects of molecular and cellular decline have been most often described as isolated or distinct mechanisms. However, there is significant evidence demonstrating interplay between ... ...

Abstract	Since the identification and definition of the hallmarks of aging, these aspects of molecular and cellular decline have been most often described as isolated or distinct mechanisms. However, there is significant evidence demonstrating interplay between most of these hallmarks and that they have the capacity to influence and regulate one another. These interactions are demonstrable across the tree of life, yet not all aspects are conserved. Here, we describe an integrative view on the hallmarks of aging by using the hallmark "mitochondrial dysfunction" as a focus point, and illustrate its capacity to both influence and be influenced by the other hallmarks of aging. We discuss the effects of mitochondrial pathways involved in aging, such as oxidative phosphorylation, mitochondrial dynamics, mitochondrial protein synthesis, mitophagy, reactive oxygen species and mitochondrial DNA damage in relation to each of the primary, antagonistic and integrative hallmarks. We discuss the similarities and differences in these interactions throughout the tree of life, and speculate how speciation may play a role in the variation in these mechanisms. We propose that the hallmarks are critically intertwined, and that mapping the full extent of these interactions would be of significant benefit to the aging research community.
Language	English
Publishing date	2020-11-26
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2737824-X
ISSN	2296-634X
ISSN	2296-634X
DOI	10.3389/fcell.2020.594416
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: A conserved complex lipid signature marks human muscle aging and responds to short-term exercise.

Janssens, Georges E / Molenaars, Marte / Herzog, Katharina / Grevendonk, Lotte / Remie, Carlijn M E / Vervaart, Martin A T / Elfrink, Hyung L / Wever, Eric J M / Schomakers, Bauke V / Denis, Simone W / Waterham, Hans R / Pras-Raves, Mia L / van Weeghel, Michel / van Kampen, Antoine H C / Tammaro, Alessandra / Butter, Loes M / van der Rijt, Sanne / Florquin, Sandrine / Jongejan, Aldo /

Moerland, Perry D / Hoeks, Joris / Schrauwen, Patrick / Vaz, Frédéric M / Houtkooper, Riekelt H

Nature aging

2024

Abstract: Studies in preclinical models suggest that complex lipids, such as phospholipids, play a role in the regulation of longevity. However, identification of universally conserved complex lipid changes that occur during aging, and how these respond to ... ...

Abstract	Studies in preclinical models suggest that complex lipids, such as phospholipids, play a role in the regulation of longevity. However, identification of universally conserved complex lipid changes that occur during aging, and how these respond to interventions, is lacking. Here, to comprehensively map how complex lipids change during aging, we profiled ten tissues in young versus aged mice using a lipidomics platform. Strikingly, from >1,200 unique lipids, we found a tissue-wide accumulation of bis(monoacylglycero)phosphate (BMP) during mouse aging. To investigate translational value, we assessed muscle tissue of young and older people, and found a similar marked BMP accumulation in the human aging lipidome. Furthermore, we found that a healthy-aging intervention consisting of moderate-to-vigorous exercise was able to lower BMP levels in postmenopausal female research participants. Our work implicates complex lipid biology as central to aging, identifying a conserved aging lipid signature of BMP accumulation that is modifiable upon a short-term healthy-aging intervention.
Language	English
Publishing date	2024-04-12
Publishing country	United States
Document type	Journal Article
ISSN	2662-8465
ISSN (online)	2662-8465
DOI	10.1038/s43587-024-00595-2
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article ; Online: Mitochondrial ubiquinone-mediated longevity is marked by reduced cytoplasmic mRNA translation.

Molenaars, Marte / Janssens, Georges E / Santermans, Toon / Lezzerini, Marco / Jelier, Rob / MacInnes, Alyson W / Houtkooper, Riekelt H

Life science alliance

2018 Volume 1, Issue 5

Abstract: Mutations in ... ...

Abstract	Mutations in the
Language	English
Publishing date	2018-08-24
Publishing country	United States
Document type	Journal Article
ISSN	2575-1077
ISSN (online)	2575-1077
DOI	10.26508/lsa.201800082
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article ; Online: Metabolomics and lipidomics in Caenorhabditis elegans using a single-sample preparation.

Molenaars, Marte / Schomakers, Bauke V / Elfrink, Hyung L / Gao, Arwen W / Vervaart, Martin A T / Pras-Raves, Mia L / Luyf, Angela C / Smith, Reuben L / Sterken, Mark G / Kammenga, Jan E / van Kampen, Antoine H C / Janssens, Georges E / Vaz, Frédéric M / van Weeghel, Michel / Houtkooper, Riekelt H

Disease models & mechanisms

2021 Volume 14, Issue 4

Abstract: Comprehensive metabolomic and lipidomic mass spectrometry methods are in increasing demand; for instance, in research related to nutrition and aging. The nematode Caenorhabditis elegans is a key model organism in these fields, owing to the large ... ...

Abstract	Comprehensive metabolomic and lipidomic mass spectrometry methods are in increasing demand; for instance, in research related to nutrition and aging. The nematode Caenorhabditis elegans is a key model organism in these fields, owing to the large repository of available C. elegans mutants and their convenient natural lifespan. Here, we describe a robust and sensitive analytical method for the semi-quantitative analysis of >100 polar (metabolomics) and >1000 apolar (lipidomics) metabolites in C. elegans, using a single-sample preparation. Our method is capable of reliably detecting a wide variety of biologically relevant metabolic aberrations in, for example, glycolysis and the tricarboxylic acid cycle, pyrimidine metabolism and complex lipid biosynthesis. In conclusion, we provide a powerful analytical tool that maximizes metabolic data yield from a single sample. This article has an associated First Person interview with the joint first authors of the paper.
MeSH term(s)	Animals ; Caenorhabditis elegans/genetics ; Caenorhabditis elegans/metabolism ; Gene Knockdown Techniques ; Inbreeding ; Lipidomics/methods ; Metabolome ; Metabolomics/methods ; Phospholipids/metabolism ; RNA Interference ; Reproducibility of Results
Chemical Substances	Phospholipids
Language	English
Publishing date	2021-04-27
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2451104-3
ISSN	1754-8411 ; 1754-8403
ISSN (online)	1754-8411
ISSN	1754-8403
DOI	10.1242/dmm.047746
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: Inhibition of the neuromuscular acetylcholine receptor with atracurium activates FOXO/DAF-16-induced longevity.

McIntyre, Rebecca L / Denis, Simone W / Kamble, Rashmi / Molenaars, Marte / Petr, Michael / Schomakers, Bauke V / Rahman, Mizanur / Gupta, Siddhartha / Toth, Marton L / Vanapalli, Siva A / Jongejan, Aldo / Scheibye-Knudsen, Morten / Houtkooper, Riekelt H / Janssens, Georges E

Aging cell

2021 Volume 20, Issue 8, Page(s) e13381

Abstract: Transcriptome-based drug screening is emerging as a powerful tool to identify geroprotective compounds to intervene in age-related disease. We hypothesized that, by mimicking the transcriptional signature of the highly conserved longevity intervention of ...

Abstract	Transcriptome-based drug screening is emerging as a powerful tool to identify geroprotective compounds to intervene in age-related disease. We hypothesized that, by mimicking the transcriptional signature of the highly conserved longevity intervention of FOXO3 (daf-16 in worms) overexpression, we could identify and repurpose compounds with similar downstream effects to increase longevity. Our in silico screen, utilizing the LINCS transcriptome database of genetic and compound interventions, identified several FDA-approved compounds that activate FOXO downstream targets in mammalian cells. These included the neuromuscular blocker atracurium, which also robustly extends both lifespan and healthspan in Caenorhabditis elegans. This longevity is dependent on both daf-16 signaling and inhibition of the neuromuscular acetylcholine receptor subunit unc-38. We found unc-38 RNAi to improve healthspan, lifespan, and stimulate DAF-16 nuclear localization, similar to atracurium treatment. Finally, using RNA-seq transcriptomics, we identify atracurium activation of DAF-16 downstream effectors. Together, these data demonstrate the capacity to mimic genetic lifespan interventions with drugs, and in doing so, reveal that the neuromuscular acetylcholine receptor regulates the highly conserved FOXO/DAF-16 longevity pathway.
MeSH term(s)	Animals ; Atracurium/pharmacology ; Atracurium/therapeutic use ; Caenorhabditis elegans/genetics ; Caenorhabditis elegans Proteins/metabolism ; Forkhead Transcription Factors/metabolism ; Longevity/genetics ; Mice ; Receptors, Cholinergic/metabolism
Chemical Substances	Caenorhabditis elegans Proteins ; Forkhead Transcription Factors ; Receptors, Cholinergic ; daf-16 protein, C elegans ; Atracurium (2GQ1IRY63P)
Language	English
Publishing date	2021-07-06
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2113083-8
ISSN	1474-9726 ; 1474-9718
ISSN (online)	1474-9726
ISSN	1474-9718
DOI	10.1111/acel.13381
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 6581: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Glycine promotes longevity in Caenorhabditis elegans in a methionine cycle-dependent fashion.

Liu, Yasmine J / Janssens, Georges E / McIntyre, Rebecca L / Molenaars, Marte / Kamble, Rashmi / Gao, Arwen W / Jongejan, Aldo / Weeghel, Michel van / MacInnes, Alyson W / Houtkooper, Riekelt H

PLoS genetics

2019 Volume 15, Issue 3, Page(s) e1007633

Abstract: The deregulation of metabolism is a hallmark of aging. As such, changes in the expression of metabolic genes and the profiles of amino acid levels are features associated with aging animals. We previously reported that the levels of most amino acids ... ...

Abstract	The deregulation of metabolism is a hallmark of aging. As such, changes in the expression of metabolic genes and the profiles of amino acid levels are features associated with aging animals. We previously reported that the levels of most amino acids decline with age in Caenorhabditis elegans (C. elegans). Glycine, in contrast, substantially accumulates in aging C. elegans. In this study we show that this is coupled to a decrease in gene expression of enzymes important for glycine catabolism. We further show that supplementation of glycine significantly prolongs C. elegans lifespan, and early adulthood is important for its salutary effects. Moreover, supplementation of glycine ameliorates specific transcriptional changes that are associated with aging. Glycine feeds into the methionine cycle. We find that mutations in components of this cycle, methionine synthase (metr-1) and S-adenosylmethionine synthetase (sams-1), completely abrogate glycine-induced lifespan extension. Strikingly, the beneficial effects of glycine supplementation are conserved when we supplement with serine, which also feeds into the methionine cycle. RNA-sequencing reveals a similar transcriptional landscape in serine- and glycine-supplemented worms both demarked by widespread gene repression. Taken together, these data uncover a novel role of glycine in the deceleration of aging through its function in the methionine cycle.
MeSH term(s)	Aging/drug effects ; Aging/genetics ; Aging/metabolism ; Animals ; Caenorhabditis elegans/drug effects ; Caenorhabditis elegans/genetics ; Caenorhabditis elegans/metabolism ; Diet ; Genes, Helminth ; Glycine/administration & dosage ; Glycine/metabolism ; Longevity/drug effects ; Longevity/genetics ; Longevity/physiology ; Metabolic Networks and Pathways/genetics ; Methionine/metabolism ; Mutation ; RNA Interference ; Serine/administration & dosage ; Serine/metabolism ; Transcriptome/drug effects
Chemical Substances	Serine (452VLY9402) ; Methionine (AE28F7PNPL) ; Glycine (TE7660XO1C)
Language	English
Publishing date	2019-03-07
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2186725-2
ISSN	1553-7404 ; 1553-7390
ISSN (online)	1553-7404
ISSN	1553-7390
DOI	10.1371/journal.pgen.1007633
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

To top

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Order via subito

More links

Kategorien

Order via subito

Inter-library loan at ZB MED

More links

Kategorien

Order via subito

More links

Kategorien

Order via subito

Inter-library loan at ZB MED

More links

Kategorien

Order via subito

Inter-library loan at ZB MED

More links

Kategorien

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Order via subito