Two modes of mitochondrial dysfunction lead independently to lifespan extension in <i>Caenorhabditis elegans</i>
Bibliographic record
Abstract
In Caenorhabditis elegans, longevity is increased by a partial loss-of-function mutation in the mitochondrial complex III subunit gene isp-1. Longevity is also increased by RNAi against the expression of a variety of mitochondrial respiratory chain genes, including isp-1, but it is unknown whether the isp-1(qm150) mutation and the RNAi treatments trigger the same underlying mechanisms of longevity. We have identified nuo-6(qm200), a mutation in a conserved subunit of mitochondrial complex I (NUDFB4). The mutation reduces the function of complex I and, like isp-1(qm150), results in low oxygen consumption, slow growth, slow behavior, and increased lifespan. We have compared the phenotypes of nuo-6(qm200) to those of nuo-6(RNAi) and found them to be distinct in crucial ways, including patterns of growth and fertility, behavioral rates, oxygen consumption, ATP levels, autophagy, and resistance to paraquat, as well as expression of superoxide dismutases, mitochondrial heat-shock proteins, and other gene expression markers. RNAi treatments appear to generate a stress and autophagy response, while the genomic mutation alters electron transport and reactive oxygen species metabolism. For many phenotypes, we also compared isp-1(qm150) to isp-1(RNAi) and found the same pattern of differences. Most importantly, we found that, while the lifespan of nuo-6, isp-1 double mutants is not greater than that of the single mutants, the lifespan increase induced by nuo-6(RNAi) is fully additive to that induced by isp-1(qm150), and the increase induced by isp-1(RNAi) is fully additive to that induced by nuo-6(qm200). Our results demonstrate that distinct and separable aspects of mitochondrial biology affect lifespan independently.
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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) | 0.001 | 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) | 0.001 | 0.000 |
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.
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".