ins-1
C. elegans
Insulin-like peptide INSL5
What the model saw
Gene: ins-1 Organism: Caenorhabditis elegans Known functions: Insulin-like peptide INSL5. hormone activity.
View unredacted entry
Insulin-like peptide INSL5. hormone activity.
Solver output
ins-1 encodes an insulin-like peptide in C. elegans that acts as a ligand for the DAF-2 insulin/IGF-1 receptor. Activation of DAF-2 by insulin-like peptides triggers the PI3K/AKT signaling cascade, which phosphorylates and cytoplasmatically sequesters the FOXO transcription factor DAF-16. DAF-16 nuclear exclusion suppresses expression of stress-resistance, detoxification, and longevity-promoting genes. Reduced insulin/IGF-1 signaling (e.g., daf-2 loss-of-function) is one of the most robust pro-longevity interventions in C. elegans, doubling lifespan in a DAF-16-dependent manner. Therefore, ins-1, as an agonist ligand driving DAF-2 activation, opposes longevity by promoting DAF-16 inhibition and suppressing the transcriptional longevity program.
GenAge curators classify each gene's normal function as promoting (Pro-Longevity) or opposing (Anti-Longevity) longevity, based on synthesis across studies. Loss-of-function effects can vary from this depending on the manipulation.
Advisor judgment
The model predicted anti_longevity but the ground truth is pro_longevity. The model's reasoning follows the general logic that insulin-like peptides activate DAF-2, which suppresses DAF-16 and thus reduces longevity. However, ins-1 in C. elegans is actually an antagonist of DAF-2 signaling (not an agonist), acting as a partial agonist/antagonist that competes with other insulin-like peptides and can actually promote longevity by dampening IIS. The model incorrectly assumed ins-1 is a straightforward agonist of DAF-2, when in fact it has been shown to act as an antagonist ligand that reduces DAF-2 signaling, thereby promoting DAF-16 nuclear localization and extending lifespan. The reasoning quality is moderate — the general framework about IIS pathway is correct, but the specific role of ins-1 as an antagonist rather than agonist was missed, leading to the wrong conclusion with high confidence (0.78).
Raw API responses
solver
{
"reasoning": "ins-1 encodes an insulin-like peptide in C. elegans that acts as a ligand for the DAF-2 insulin/IGF-1 receptor. Activation of DAF-2 by insulin-like peptides triggers the PI3K/AKT signaling cascade, which phosphorylates and cytoplasmatically sequesters the FOXO transcription factor DAF-16. DAF-16 nuclear exclusion suppresses expression of stress-resistance, detoxification, and longevity-promoting genes. Reduced insulin/IGF-1 signaling (e.g., daf-2 loss-of-function) is one of the most robust pro-longevity interventions in C. elegans, doubling lifespan in a DAF-16-dependent manner. Therefore, ins-1, as an agonist ligand driving DAF-2 activation, opposes longevity by promoting DAF-16 inhibition and suppressing the transcriptional longevity program.",
"confidence": 0.78,
"key_pathways": [
"Insulin/IGF-1 signaling (IIS) pathway",
"DAF-2/DAF-16 axis",
"PI3K/AKT nutrient-sensing cascade"
],
"mechanism_class": "deregulated_nutrient_sensing",
"longevity_influence": "anti_longevity"
}advisor
{
"notes": "The model predicted anti_longevity but the ground truth is pro_longevity. The model's reasoning follows the general logic that insulin-like peptides activate DAF-2, which suppresses DAF-16 and thus reduces longevity. However, ins-1 in C. elegans is actually an antagonist of DAF-2 signaling (not an agonist), acting as a partial agonist/antagonist that competes with other insulin-like peptides and can actually promote longevity by dampening IIS. The model incorrectly assumed ins-1 is a straightforward agonist of DAF-2, when in fact it has been shown to act as an antagonist ligand that reduces DAF-2 signaling, thereby promoting DAF-16 nuclear localization and extending lifespan. The reasoning quality is moderate — the general framework about IIS pathway is correct, but the specific role of ins-1 as an antagonist rather than agonist was missed, leading to the wrong conclusion with high confidence (0.78).",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 3,
"ground_truth_questionable": false
}