Ilp6
D. melanogaster
Insulin-like peptide 6
What the model saw
Gene: Ilp6 Organism: Drosophila melanogaster Known functions: Insulin-like peptide 6. insulin receptor binding. receptor ligand activity.
View unredacted entry
Insulin-like peptide 6. insulin receptor binding. receptor ligand activity.
Solver output
Ilp6 encodes an insulin-like peptide that binds and activates the Drosophila insulin receptor (dInR), thereby stimulating the canonical insulin/IGF-1 signaling (IIS) pathway. Activation of IIS leads to PI3K/Akt-mediated phosphorylation and cytoplasmic retention of the FOXO transcription factor dFOXO, suppressing its pro-longevity transcriptional program. Elevated IIS is well-established as a major driver of reduced lifespan in Drosophila, as loss-of-function mutations in the pathway (e.g., chico, dInR) or overexpression of dFOXO extend lifespan. As a ligand that positively activates this pathway, Ilp6's normal function promotes IIS activity and thus opposes longevity. This places it squarely within the deregulated nutrient-sensing hallmark of aging, specifically the insulin/IGF-1 axis.
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 with high confidence (0.82), but the ground truth is pro_longevity. The model applied a generic IIS reasoning: Ilp6 activates insulin receptor → activates IIS → suppresses dFOXO → reduces lifespan. However, Ilp6 is atypical among Drosophila insulin-like peptides. Research has shown that Ilp6 is upregulated during starvation and acts in a context-specific manner that can actually promote longevity, possibly through fat body signaling or by acting as a partial agonist/modulator rather than a full activator of IIS. The model's reasoning is plausible for most ILPs but fails to account for the specific biology of Ilp6, which differs from Ilp2/3/5 in its expression pattern and functional role. The reasoning quality is moderate — it's logically coherent but applies an oversimplified framework that misses the nuance of this particular gene.
Raw API responses
solver
{
"reasoning": "Ilp6 encodes an insulin-like peptide that binds and activates the Drosophila insulin receptor (dInR), thereby stimulating the canonical insulin/IGF-1 signaling (IIS) pathway. Activation of IIS leads to PI3K/Akt-mediated phosphorylation and cytoplasmic retention of the FOXO transcription factor dFOXO, suppressing its pro-longevity transcriptional program. Elevated IIS is well-established as a major driver of reduced lifespan in Drosophila, as loss-of-function mutations in the pathway (e.g., chico, dInR) or overexpression of dFOXO extend lifespan. As a ligand that positively activates this pathway, Ilp6's normal function promotes IIS activity and thus opposes longevity. This places it squarely within the deregulated nutrient-sensing hallmark of aging, specifically the insulin/IGF-1 axis.",
"confidence": 0.82,
"key_pathways": [
"Insulin/IGF-1 signaling (IIS)",
"PI3K/Akt/dFOXO axis",
"dInR receptor activation"
],
"mechanism_class": "deregulated_nutrient_sensing",
"longevity_influence": "anti_longevity"
}advisor
{
"notes": "The model predicted anti_longevity with high confidence (0.82), but the ground truth is pro_longevity. The model applied a generic IIS reasoning: Ilp6 activates insulin receptor → activates IIS → suppresses dFOXO → reduces lifespan. However, Ilp6 is atypical among Drosophila insulin-like peptides. Research has shown that Ilp6 is upregulated during starvation and acts in a context-specific manner that can actually promote longevity, possibly through fat body signaling or by acting as a partial agonist/modulator rather than a full activator of IIS. The model's reasoning is plausible for most ILPs but fails to account for the specific biology of Ilp6, which differs from Ilp2/3/5 in its expression pattern and functional role. The reasoning quality is moderate — it's logically coherent but applies an oversimplified framework that misses the nuance of this particular gene.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 3,
"ground_truth_questionable": false
}