MetaFlex SIGNED
Metabolic flexibility: breaking down food effectively to prolong life
Total Cost €
0EC-Contrib. €
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Project "MetaFlex" data sheet
The following table provides information about the project.
| Coordinator |
ACADEMISCH MEDISCH CENTRUM BIJ DE UNIVERSITEIT VAN AMSTERDAM
Organization address contact info |
| Coordinator Country | Netherlands [NL] |
| Total cost | 1˙499˙446 € |
| EC max contribution | 1˙499˙446 € (100%) |
| Programme |
1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC)) |
| Code Call | ERC-2014-STG |
| Funding Scheme | ERC-STG |
| Starting year | 2015 |
| Duration (year-month-day) | from 2015-04-01 to 2020-03-31 |
Partnership
Take a look of project's partnership.
| # | ||||
|---|---|---|---|---|
| 1 | ACADEMISCH MEDISCH CENTRUM BIJ DE UNIVERSITEIT VAN AMSTERDAM | NL (AMSTERDAM) | coordinator | 1˙499˙446.00 |
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Project objective
Aging has long been considered a passive process. More recently studies have defined an important, active role for metabolic pathways in aging and age-related diseases. I have previously demonstrated a marked dysregulation of fat metabolism in aged mice that contributes to their overweight and glucose intolerance. Here, I propose a model that links healthy aging to efficient processing of nutrients, a state termed metabolic flexibility: reducing protein or carbohydrate metabolism will strongly stimulate fat breakdown. I suggest that improved metabolic flexibility will thus prevent the accumulation of lipids and protect against its detrimental effects.
In this project, I aim to elucidate how nutrient breakdown is regulated and can be adapted to improve metabolic flexibility and promote healthy aging. I will use C. elegans, as well as mammalian models and human population studies. Specifically, I aim to (1) dissect the molecular actors of metabolic aging pathways; (2) identify genes that translate nutritional cues to lifespan variation; (3) find novel genetic regulators that prevent toxicity and accelerated aging caused by fat-rich diets; (4) identify associations between variants in genes involved in metabolic flexibility and aging phenotypes in humans.
This set of experiments should clarify the role of nutrient breakdown and metabolic flexibility in aging. Better understanding of these processes can lead to a prolonged healthy state of aged individuals.
Publications
| year | authors and title | journal | last update |
|---|---|---|---|
| 2018 |
Ntsiki M. Held, Eline N. Kuipers, Michel van Weeghel, Jan Bert van Klinken, Simone W. Denis, Marc Lombès, Ronald J. Wanders, Frédéric M. Vaz, Patrick C. N. Rensen, Arthur J. Verhoeven, Mariëtte R. Boon, Riekelt H. Houtkooper Pyruvate dehydrogenase complex plays a central role in brown adipocyte energy expenditure and fuel utilization during short-term beta-adrenergic activation published pages: , ISSN: 2045-2322, DOI: 10.1038/s41598-018-27875-3 |
Scientific Reports 8/1 | 2019-11-22 |
| 2018 |
Marte Molenaars, Georges E Janssens, Toon Santermans, Marco Lezzerini, Rob Jelier, Alyson W MacInnes, Riekelt H Houtkooper Mitochondrial ubiquinone–mediated longevity is marked by reduced cytoplasmic mRNA translation published pages: e201800082, ISSN: 2575-1077, DOI: 10.26508/lsa.201800082 |
Life Science Alliance 1/5 | 2019-11-22 |
| 2019 |
Yasmine J. Liu, Georges E. Janssens, Rebecca L. McIntyre, Marte Molenaars, Rashmi Kamble, Arwen W. Gao, Aldo Jongejan, Michel van Weeghel, Alyson W. MacInnes, Riekelt H. Houtkooper Glycine promotes longevity in Caenorhabditis elegans in a methionine cycle-dependent fashion published pages: e1007633, ISSN: 1553-7404, DOI: 10.1371/journal.pgen.1007633 |
PLOS Genetics 15/3 | 2019-11-22 |
| 2019 |
Rebecca L McIntyre, Eileen G Daniels, Marte Molenaars, Riekelt H Houtkooper, Georges E Janssens From molecular promise to preclinical results: HDAC inhibitors in the race for healthy aging drugs published pages: , ISSN: 1757-4676, DOI: 10.15252/emmm.201809854 |
EMBO Molecular Medicine 11/9 | 2019-11-22 |
| 2018 |
Arwen W. Gao, Mark G. Sterken, Jelmi uit de Bos, Jelle van Creij, Rashmi Kamble, Basten L. Snoek, Jan E. Kammenga, Riekelt H. Houtkooper Natural genetic variation in C. elegans identified genomic loci controlling metabolite levels published pages: 1296-1308, ISSN: 1088-9051, DOI: 10.1101/gr.232322.117 |
Genome Research 28/9 | 2019-11-22 |
| 2016 |
Jeannette C. Bleeker, Riekelt H. Houtkooper Sirtuin activation as a therapeutic approach against inborn errors of metabolism published pages: 565-572, ISSN: 0141-8955, DOI: 10.1007/s10545-016-9939-8 |
Journal of Inherited Metabolic Disease 39/4 | 2019-09-02 |
| 2015 |
I. A. Chatzispyrou, N. M. Held, L. Mouchiroud, J. Auwerx, R. H. Houtkooper Tetracycline Antibiotics Impair Mitochondrial Function and Its Experimental Use Confounds Research published pages: 4446-4449, ISSN: 0008-5472, DOI: 10.1158/0008-5472.CAN-15-1626 |
Cancer Research 75/21 | 2019-09-02 |
| 2015 |
Ntsiki M. Held, Riekelt H. Houtkooper Mitochondrial quality control pathways as determinants of metabolic health published pages: 867-876, ISSN: 0265-9247, DOI: 10.1002/bies.201500013 |
BioEssays 37/8 | 2019-09-02 |
| 2016 |
Mandy Koopman, Helen Michels, Beverley M Dancy, Rashmi Kamble, Laurent Mouchiroud, Johan Auwerx, Ellen A A Nollen, Riekelt H Houtkooper A screening-based platform for the assessment of cellular respiration in Caenorhabditis elegans published pages: 1798-1816, ISSN: 1754-2189, DOI: 10.1038/nprot.2016.106 |
Nature Protocols 11/10 | 2019-09-02 |
| 2017 |
Arwen W. Gao, Jelmi uit de Bos, Mark G. Sterken, Jan E. Kammenga, Reuben L. Smith, Riekelt H. Houtkooper Forward and reverse genetics approaches to uncover metabolic aging pathways in Caenorhabditis elegans published pages: , ISSN: 0925-4439, DOI: 10.1016/j.bbadis.2017.09.006 |
Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease | 2019-09-02 |
| 2017 |
Arwen W. Gao, Iliana A. Chatzispyrou, Rashmi Kamble, Yasmine J. Liu, Katharina Herzog, Reuben L. Smith, Henk van Lenthe, Martin A. T. Vervaart, Arno van Cruchten, Angela C. Luyf, Antoine van Kampen, Mia L. Pras-Raves, Frédéric M. Vaz, Riekelt H. Houtkooper A sensitive mass spectrometry platform identifies metabolic changes of life history traits in C. elegans published pages: , ISSN: 2045-2322, DOI: 10.1038/s41598-017-02539-w |
Scientific Reports 7/1 | 2019-09-02 |
| 2015 |
Xu Wang, Dongryeol Ryu, Riekelt H. Houtkooper, Johan Auwerx Antibiotic use and abuse: A threat to mitochondria and chloroplasts with impact on research, health, and environment published pages: 1045-1053, ISSN: 0265-9247, DOI: 10.1002/bies.201500071 |
BioEssays 37/10 | 2019-09-02 |
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