Indy
D. melanogaster
I'm not dead yet
What the model saw
Gene: Indy Organism: Drosophila melanogaster Known functions: I'm not dead yet. citrate transmembrane transporter activity. pyruvate transmembrane transporter activity. succinate transmembrane transporter activity. transmembrane transporter activity.
View unredacted entry
I'm not dead yet. citrate transmembrane transporter activity. pyruvate transmembrane transporter activity. succinate transmembrane transporter activity. transmembrane transporter activity.
Solver output
Indy (I'm Not Dead Yet) encodes a plasma membrane transporter on intestinal and fat body cells that imports Krebs cycle intermediates — citrate, succinate, and pyruvate — from the gut lumen and hemolymph into cells. By facilitating uptake of these TCA cycle substrates, Indy effectively increases the intracellular availability of metabolic fuel, mimicking a caloric-excess state. Loss-of-function mutations in Indy reduce citrate/succinate import, lower cytoplasmic acetyl-CoA availability, and phenocopy caloric restriction, activating AMPK and suppressing insulin/IGF-1 signaling (IIS) and TOR pathways. This metabolic shift extends lifespan in Drosophila, demonstrating that the normal (wild-type) function of Indy — promoting nutrient uptake — is anti-longevity. The gene's activity thus opposes longevity by sustaining high nutrient flux that keeps pro-aging anabolic signaling elevated.
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 correctly identified Indy as anti_longevity with high confidence (0.92). The mechanistic reasoning is excellent and accurate: Indy encodes a transporter for TCA cycle intermediates (citrate, succinate, pyruvate), and its loss-of-function mimics caloric restriction to extend lifespan, meaning the wild-type gene is anti-longevity. The model correctly identifies the key pathways (IIS, AMPK/TOR, caloric restriction mimicry) and provides a coherent, well-supported explanation. This is a well-known Drosophila aging gene and the model's reasoning aligns with the published literature.
Raw API responses
solver
{
"reasoning": "Indy (I'm Not Dead Yet) encodes a plasma membrane transporter on intestinal and fat body cells that imports Krebs cycle intermediates — citrate, succinate, and pyruvate — from the gut lumen and hemolymph into cells. By facilitating uptake of these TCA cycle substrates, Indy effectively increases the intracellular availability of metabolic fuel, mimicking a caloric-excess state. Loss-of-function mutations in Indy reduce citrate/succinate import, lower cytoplasmic acetyl-CoA availability, and phenocopy caloric restriction, activating AMPK and suppressing insulin/IGF-1 signaling (IIS) and TOR pathways. This metabolic shift extends lifespan in Drosophila, demonstrating that the normal (wild-type) function of Indy — promoting nutrient uptake — is anti-longevity. The gene's activity thus opposes longevity by sustaining high nutrient flux that keeps pro-aging anabolic signaling elevated.",
"confidence": 0.92,
"key_pathways": [
"insulin/IGF-1 signaling (IIS)",
"TCA cycle intermediate transport / caloric restriction mimicry",
"AMPK/TOR nutrient sensing"
],
"mechanism_class": "deregulated_nutrient_sensing",
"longevity_influence": "anti_longevity"
}advisor
{
"notes": "The model correctly identified Indy as anti_longevity with high confidence (0.92). The mechanistic reasoning is excellent and accurate: Indy encodes a transporter for TCA cycle intermediates (citrate, succinate, pyruvate), and its loss-of-function mimics caloric restriction to extend lifespan, meaning the wild-type gene is anti-longevity. The model correctly identifies the key pathways (IIS, AMPK/TOR, caloric restriction mimicry) and provides a coherent, well-supported explanation. This is a well-known Drosophila aging gene and the model's reasoning aligns with the published literature.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 5,
"ground_truth_questionable": false
}