Neuronal expression of <i>Mgat1</i> rescues the shortened life span of <i> Drosophila Mgat1 <sup>1</sup> </i> null mutants and increases life span
Bibliographic record
Abstract
The enzyme UDP-GlcNAc:alpha3-D-mannoside beta1,2-N-acetylglucosaminyltransferase I (GnT1, encoded by Mgat1) controls the synthesis of paucimannose N-glycans in Drosophila. We have previously reported that null mutations in Drosophila Mgat1 are viable but exhibit defects in locomotion, brain abnormalities, and a severely reduced life span. Here, we show that knockdown of Mgat1 in the central nervous system (CNS) of wild-type flies decreases locomotor activity and life span. This phenotype is similar to that observed in Drosophila Mgat1(1) null mutants, demonstrating that Mgat1 is required in the CNS. We also found that neuronal expression of a wild-type Mgat1 transgene rescued the shortened life span of Mgat1(1) null mutants and resulted in a dramatic 135% increase in mean life span relative to genetically identical controls. Neuronal expression of a wild-type Mgat1 transgene in wild-type flies resulted in a modest 9% increase in mean life span relative to genetically identical controls. In both Mgat1(1) null mutants and wild-type flies, neuronal expression of wild-type Mgat1 transgene resulted in a significant increase in GnT1 activity and resistance to oxidative stress. Whereas dietary restriction is not absolutely essential for the increased life span, it plays a role in the process. Interestingly, we observe a direct correlation between GnT1 activity and mean life span up to a maximum of appropriately 136 days, showing that the ability of GnT1 activity to increase life span is limited. Altogether, these observations suggest that Mgat1-dependent N-glycosylation plays an important role in the control of Drosophila life span.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
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.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".