daf-14
C. elegans
Smad-related protein daf-14
What the model saw
Gene: daf-14 Organism: Caenorhabditis elegans Known functions: Smad-related protein daf-14. DNA-binding transcription factor activity, RNA polymerase II-specific. I-SMAD binding. RNA polymerase II cis-regulatory region sequence-specific DNA binding.
View unredacted entry
Smad-related protein daf-14. DNA-binding transcription factor activity, RNA polymerase II-specific. I-SMAD binding. RNA polymerase II cis-regulatory region sequence-specific DNA binding.
Solver output
DAF-14 is a Smad-related transcription factor that functions in the C. elegans insulin/IGF-1 signaling (IIS) pathway, specifically as a co-Smad partner of DAF-3 in the TGF-β/DAF-7 branch. DAF-14 binds I-SMADs (inhibitory SMADs, such as DAF-3) and acts as a transcriptional regulator via RNA Pol II-specific DNA binding at cis-regulatory regions. In the context of the DAF-7/TGF-β pathway, DAF-14 functions alongside DAF-8 to antagonize the transcriptional repressor DAF-3, thereby promoting DAF-16-independent longevity and dauer suppression. Loss of daf-14 leads to constitutive dauer formation and shortened lifespan, indicating that its normal function suppresses pro-aging transcriptional programs driven by DAF-3. This places DAF-14 as a pro-longevity factor through its role in nutrient/growth sensing signal transduction via the TGF-β branch of neuroendocrine signaling.
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 pro_longevity but the ground truth is anti_longevity. The model's mechanistic reasoning contains errors. DAF-14 is a R-SMAD (receptor-regulated SMAD), not an I-SMAD binder in the way described. The model claims DAF-14 antagonizes DAF-3 to promote longevity, but the actual biology is more nuanced. DAF-14 functions in the TGF-β/DAF-7 pathway as a SMAD that, when active, promotes growth/reproduction signaling. Loss of daf-14 actually leads to dauer formation (a longevity-associated state), and daf-14 mutants have extended lifespan, consistent with anti_longevity classification. The model incorrectly concludes that loss of daf-14 shortens lifespan, when in fact daf-14 loss-of-function promotes dauer and longevity. The model's reasoning about DAF-14 suppressing pro-aging programs is backwards - DAF-14 activity promotes the non-dauer, shorter-lived state. The model was confident (0.78) in the wrong answer with flawed mechanistic reasoning.
Raw API responses
solver
{
"reasoning": "DAF-14 is a Smad-related transcription factor that functions in the C. elegans insulin/IGF-1 signaling (IIS) pathway, specifically as a co-Smad partner of DAF-3 in the TGF-β/DAF-7 branch. DAF-14 binds I-SMADs (inhibitory SMADs, such as DAF-3) and acts as a transcriptional regulator via RNA Pol II-specific DNA binding at cis-regulatory regions. In the context of the DAF-7/TGF-β pathway, DAF-14 functions alongside DAF-8 to antagonize the transcriptional repressor DAF-3, thereby promoting DAF-16-independent longevity and dauer suppression. Loss of daf-14 leads to constitutive dauer formation and shortened lifespan, indicating that its normal function suppresses pro-aging transcriptional programs driven by DAF-3. This places DAF-14 as a pro-longevity factor through its role in nutrient/growth sensing signal transduction via the TGF-β branch of neuroendocrine signaling.",
"confidence": 0.78,
"key_pathways": [
"TGF-β/DAF-7 signaling pathway",
"DAF-3 I-SMAD inhibition",
"Insulin/IGF-1 and neuroendocrine longevity signaling"
],
"mechanism_class": "deregulated_nutrient_sensing",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model predicted pro_longevity but the ground truth is anti_longevity. The model's mechanistic reasoning contains errors. DAF-14 is a R-SMAD (receptor-regulated SMAD), not an I-SMAD binder in the way described. The model claims DAF-14 antagonizes DAF-3 to promote longevity, but the actual biology is more nuanced. DAF-14 functions in the TGF-β/DAF-7 pathway as a SMAD that, when active, promotes growth/reproduction signaling. Loss of daf-14 actually leads to dauer formation (a longevity-associated state), and daf-14 mutants have extended lifespan, consistent with anti_longevity classification. The model incorrectly concludes that loss of daf-14 shortens lifespan, when in fact daf-14 loss-of-function promotes dauer and longevity. The model's reasoning about DAF-14 suppressing pro-aging programs is backwards - DAF-14 activity promotes the non-dauer, shorter-lived state. The model was confident (0.78) in the wrong answer with flawed mechanistic reasoning.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 2,
"ground_truth_questionable": false
}