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Record W2128588786 · doi:10.2337/db09-0567

<i>C. elegans</i> as Model for the Study of High Glucose– Mediated Life Span Reduction

2009· article· en· W2128588786 on OpenAlex
Andreas Schlotterer, G Kukudov, Farastuk Bozorgmehr, Harald Hutter, Xueliang Du, Dimitrios Oikonomou, Youssef Ibrahim, Friederike Pfisterer, Naila Rabbani, Paul J. Thornalley, Ahmed M. Sayed, Thomas Fleming, Per M. Humpert, Vedat Schwenger, Martin Zeier, A. Hamann, David M. Stern, Michael Brownlee, Angelika Bierhaus, Peter P. Nawroth, Michael Morcos

Why this work is in the frame

A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.

affAt least one author lists a Canadian institution in the pinned OpenAlex snapshot.

Bibliographic record

VenueDiabetes · 2009
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicGenetics, Aging, and Longevity in Model Organisms
Canadian institutionsSimon Fraser University
FundersBiotechnology and Biological Sciences Research Council
KeywordsMethylglyoxalGlycationLife spanCarbohydrate metabolismBiologyReactive oxygen speciesCaenorhabditis elegansModel organismBiochemistryLactoylglutathione lyaseDiabetes mellitusChemistryInternal medicineEnzymeEndocrinologyMedicineGene

Abstract

fetched live from OpenAlex

OBJECTIVE: Establishing Caenorhabditis elegans as a model for glucose toxicity-mediated life span reduction. RESEARCH DESIGN AND METHODS: C. elegans were maintained to achieve glucose concentrations resembling the hyperglycemic conditions in diabetic patients. The effects of high glucose on life span, glyoxalase-1 activity, advanced glycation end products (AGEs), and reactive oxygen species (ROS) formation and on mitochondrial function were studied. RESULTS: High glucose conditions reduced mean life span from 18.5 + or - 0.4 to 16.5 + or - 0.6 days and maximum life span from 25.9 + or - 0.4 to 23.2 + or - 0.4 days, independent of glucose effects on cuticle or bacterial metabolization of glucose. The formation of methylglyoxal-modified mitochondrial proteins and ROS was significantly increased by high glucose conditions and reduced by mitochondrial uncoupling and complex IIIQo inhibition. Overexpression of the methylglyoxal-detoxifying enzyme glyoxalase-1 attenuated the life-shortening effect of glucose by reducing AGE accumulation (by 65%) and ROS formation (by 50%) and restored mean (16.5 + or - 0.6 to 20.6 + or - 0.4 days) and maximum life span (23.2 + or - 0.4 to 27.7 + or - 2.3 days). In contrast, inhibition of glyoxalase-1 by RNAi further reduced mean (16.5 + or - 0.6 to 13.9 + or - 0.7 days) and maximum life span (23.2 + or - 0.4 to 20.3 + or - 1.1 days). The life span reduction by glyoxalase-1 inhibition was independent from the insulin signaling pathway because high glucose conditions also affected daf-2 knockdown animals in a similar manner. CONCLUSIONS: C. elegans is a suitable model organism to study glucose toxicity, in which high glucose conditions limit the life span by increasing ROS formation and AGE modification of mitochondrial proteins in a daf-2 independent manner. Most importantly, glucose toxicity can be prevented by improving glyoxalase-1-dependent methylglyoxal detoxification or preventing mitochondrial dysfunction.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.012
Threshold uncertainty score0.460

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.010
GPT teacher head0.231
Teacher spread0.220 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it