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RNA-seq of C.elegans and M.musculus in the presence and absence of D-Glucosamine (GlcN)

ABSTRACT: D-Glucosamine (2-amino-2-deoxy-D-glucose, C.A.S.# 3416-24-8) (GlcN) is a freely available and commonly used dietary supplement possibly promoting cartilage health in humans which also acts as an inhibitor of glycolysis. We here find that GlcN extends C. elegans lifespan by impairing glucose metabolism to activate AMP-activated protein kinase (AMPK/AAK2) leading to increased mitochondrial biogenesis. Consistent with the concept of mitohormesis, this promotes increased formation of mitochondrial reactive oxygen species (ROS) and p38/PMK-1-mediated stress signaling culminating in increased expression of the nematodal amino acid-transporter 1 (aat-1) gene. Ameliorating mitochondrial ROS formation as well as impairment of aat-1-expression abolishes GlcN-mediated lifespan extension in a NRF2/SKN-1-dependent fashion. Notably and unlike other calorie restriction mimetics (CRM) like 2-deoxy-D-glucose (2DG, DOG), GlcN extends lifespan of aging C57BL/6 mice (log-rank: p=0.002; cox regression: p=0.01) similarly paralleled by an induction of mitochondrial biogenesis, increased expression of several murine amino acid transporters, as well as increased amino-acid catabolism. Taken together, GlcN mimics a ketogenic diet to extend healthspan in evolutionary distinct species.

ORGANISM(S): Mus musculus Caenorhabditis elegans

PROVIDER: GSE54853 | GEO | 2014/03/07

SECONDARY ACCESSION(S): PRJNA237825

REPOSITORIES: GEO

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RNA-seq of C.elegans and M.musculus in the presence and absence of D-Glucosamine (GlcN)

Project description:D-Glucosamine (2-amino-2-deoxy-D-glucose, C.A.S.# 3416-24-8) (GlcN) is a freely available and commonly used dietary supplement possibly promoting cartilage health in humans which also acts as an inhibitor of glycolysis. We here find that GlcN extends C. elegans lifespan by impairing glucose metabolism to activate AMP-activated protein kinase (AMPK/AAK2) leading to increased mitochondrial biogenesis. Consistent with the concept of mitohormesis, this promotes increased formation of mitochondrial reactive oxygen species (ROS) and p38/PMK-1-mediated stress signaling culminating in increased expression of the nematodal amino acid-transporter 1 (aat-1) gene. Ameliorating mitochondrial ROS formation as well as impairment of aat-1-expression abolishes GlcN-mediated lifespan extension in a NRF2/SKN-1-dependent fashion. Notably and unlike other calorie restriction mimetics (CRM) like 2-deoxy-D-glucose (2DG, DOG), GlcN extends lifespan of aging C57BL/6 mice (log-rank: p=0.002; cox regression: p=0.01) similarly paralleled by an induction of mitochondrial biogenesis, increased expression of several murine amino acid transporters, as well as increased amino-acid catabolism. Taken together, GlcN mimics a ketogenic diet to extend healthspan in evolutionary distinct species. 24 samples: 12 mRNA profiles of C.elegans: 6 without GlcN and 6 with GlcN supplementaion; 12 mRNA profiles of M.musculus: 6 without GlcN and 6 with GlcN supplementaion

2014-03-07 | E-GEOD-54853 | biostudies-arrayexpress

The role of GCN2 kinase in amino acid dependent longevity and feeding behaviour in Drosophila

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.

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AMINO SUGARS RESHAPE INTERACTIONS BETWEEN STREPTOCOCCUS MUTANS AND STREPTOCOCCUS GORDONII

Project description:Amino sugars, particularly glucosamine (GlcN) and N-acetylglucosamine (GlcNAc) are abundant carbon and nitrogen sources that are continually supplied in host secretions and the diet to biofilms colonizing the human mouth. Evidence is emerging that these amino sugars may provide an ecological advantage to beneficial commensals over oral pathobionts. Here we performed transcriptome analysis on Streptococcus mutans and Streptococcus gordonii growing in single-species or dual-species cultures with glucose, GlcN or GlcNAc as the primary carbohydrate source. Compared to glucose, GlcN caused drastic transcriptomic shifts in each bacterium when they were cultured alone. Likewise, co-cultivation in the presence of GlcN yielded transcriptomic profiles that were dramatically different than the single-species results from GlcN-grown cells. In contrast, GlcNAc elicited only minor changes in the transcriptome of either organism, in both single- and dual-species cultures. Interestingly, genes involved in pyruvate metabolism were among the most significantly affected by GlcN in both species, and these changes were consistent with measurements of pyruvate in culture supernates. Differing a previous report, growth of S. mutans alone with GlcN inhibited expression of multiple operons required for mutacin production. Co-cultivation with S. gordonii consistently increased the expression by S. mutans of two manganese transporter operons (slo and mntH) and decreased expression of mutacin genes. Conversely, S. gordonii appeared to be less affected by the presence of S. mutans, but did show increases in genes for biosynthetic processes in the co-cultures. In conclusion, amino sugars profoundly altered the interactions between the pathogen and the commensal, likely by reprogramming their central metabolism.

2020-06-09 | GSE152021 | GEO

Combinatorial targeting of glycolysis and oxidative phosphorylation suppresses tumor growth and metastases.

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2012-12-31 | E-GEOD-16816 | biostudies-arrayexpress

Whey Protein-based Enteral Nutrition Support to Improve Protein Economy in Surgical Patients

Project description:A prospective, randomized and controlled study is proposed to establish whether an enteral nutrition support regimen based on pressurized whey protein and glucose improves the postoperative utilization of amino acid substrates compared to a drink based on glucose alone. The kinetics of protein metabolism (protein breakdown, protein synthesis and amino acid oxidation) will be investigated using stable isotope methodology before and after surgery in patients undergoing colon resection. Stable isotope infusions will be conducted one week before surgery and on the second postoperative day for two hours in the fasted state and for four hours while sipping the enteral nutrition support regimen. Patients will consume one of two enteral nutrition support regimens consisting of a drink containing either pressurized whey protein and glucose or glucose alone. It is hypothesized that an enteral nutrition support regimen based on pressurized whey protein and glucose promotes positive protein balance through increased protein synthesis or reduced protein breakdown compared to glucose alone.

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SRT2104 extends survival of male mice on a standard diet and preserves bone and muscle mass

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2014-09-22 | GSE49000 | GEO

PPARM-NM-4 activation in human myotubes increases mitochondrial fatty acid oxidative capacity and reduces glucose utilization by a switch in substrate preference.

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2014-05-23 | E-GEOD-40789 | biostudies-arrayexpress

Expression analysis of Saccharomyces cerevisiae wild-type and rph1Δ two and 24 hours following menadione treatment

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.

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2022-10-11 | E-MTAB-12060 | biostudies-arrayexpress

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