Mitochondrial dysfunction and reactive oxygen species metabolism in the aging process of «Caenorhabditis elegans»
Bibliographic record
Abstract
The nematode roundworm Caenorhabditis elegans has been extensively used to study the genetics of aging. The functions of many genes have been found to be able to affect this animal's lifespan. A large proportion of these genes are expressed in mitochondria, an organelle that plays important roles in energy metabolism and generates reactive oxygen species (ROS). These two characteristics of mitochondria have both been suggested to be crucial for lifespan determination. One hypothesis, called the oxidative stress theory of aging, proposes that high oxidative damage caused by ROS generated in mitochondria is the cause of aging. We found that the lifespan-increasing effect of electron transport chain (ETC) mutants (i.e. isp-1 and clk-1) as well as of several other long-lived mutants is not due to low oxidative damage, and that increasing oxidative damage fails to shorten their lifespan. I also identified a new long-lived mutant in a previously uncharacterized gene --nuo-6(qm200)--, which encodes the C. elegans orthologue of the B15 subunit of mammalian mitochondrial complex I. I found that this new mutation increases lifespan through the same pathway as isp-1(qm150) the previously characterized mutation in the iron sulphur subunit of complex III. Using RNA interference to knock down the level of expression of many mitochondrial genes has been found to increase the lifespan of C. elegans and of Drosophila by a mechanism that was assumed to be identical to that at work in mutations that altered the function of mitochondrial proteins. However, using the isp-1 and nuo-6 mutations I have shown that the mechanism that allows these mutants to be long-lived is, unexpectedly, completely distinct from the mechanism triggered by RNAi. Finally, I found that the generation of superoxide (a reactive oxygen species) is actually increased in these mutants, and that this elevation is necessary and sufficient for longevity. These studies challenge the traditional view about the role
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot 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.
Codex and Gemma teacher scores by category
| 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 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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 teacher head, 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".