Akt
D. melanogaster
Akt kinase
What the model saw
Gene: Akt Organism: Drosophila melanogaster Known functions: Akt kinase. ATP binding. protein binding. protein kinase activity. protein serine kinase activity. protein serine/threonine kinase activity.
View unredacted entry
Akt kinase. ATP binding. protein binding. protein kinase activity. protein serine kinase activity. protein serine/threonine kinase activity.
Solver output
Akt (also known as PKB) is the central serine/threonine kinase of the insulin/IGF-1 signaling (IIS) pathway. In Drosophila, Akt phosphorylates and inactivates FOXO (dFOXO), a transcription factor that promotes stress resistance, autophagy, and longevity-associated gene expression. Elevated IIS/Akt activity suppresses dFOXO nuclear localization, thereby reducing expression of protective genes and shortening lifespan. Conversely, reduced Akt activity or loss-of-function extends lifespan in flies, consistent with findings across multiple model organisms. Akt also phosphorylates and activates TOR complex signaling (via TSC1/2 inhibition), further amplifying nutrient-sensing pathways that are well-established drivers of aging when chronically active. Thus, the normal (wild-type) function of Akt opposes longevity by sustaining IIS-driven suppression of FOXO and activation of TORC1.
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 (0.88), but the ground truth is pro_longevity. The model's reasoning is mechanistically coherent in describing how Akt suppresses FOXO and activates TORC1, which are indeed established aging-related pathways. However, the model conflated "reduced Akt activity extends lifespan" with "Akt is anti-longevity," which is the standard IIS narrative. In Drosophila, the GenAge classification of Akt as pro_longevity likely reflects that some level of Akt activity is required for normal survival/longevity, or that overexpression/activation studies in specific tissues (e.g., muscle or nervous system) can extend lifespan. The model's reasoning is one-sided and ignores the complexity that Akt can be pro-longevity in certain contexts in Drosophila. The model was confidently wrong about the direction of effect.
Raw API responses
solver
{
"reasoning": "Akt (also known as PKB) is the central serine/threonine kinase of the insulin/IGF-1 signaling (IIS) pathway. In Drosophila, Akt phosphorylates and inactivates FOXO (dFOXO), a transcription factor that promotes stress resistance, autophagy, and longevity-associated gene expression. Elevated IIS/Akt activity suppresses dFOXO nuclear localization, thereby reducing expression of protective genes and shortening lifespan. Conversely, reduced Akt activity or loss-of-function extends lifespan in flies, consistent with findings across multiple model organisms. Akt also phosphorylates and activates TOR complex signaling (via TSC1/2 inhibition), further amplifying nutrient-sensing pathways that are well-established drivers of aging when chronically active. Thus, the normal (wild-type) function of Akt opposes longevity by sustaining IIS-driven suppression of FOXO and activation of TORC1.",
"confidence": 0.88,
"key_pathways": [
"Insulin/IGF-1 signaling (IIS) → Akt → dFOXO suppression",
"Akt → TSC1/2 inhibition → TORC1 activation",
"Nutrient sensing / mTOR pathway"
],
"mechanism_class": "deregulated_nutrient_sensing",
"longevity_influence": "anti_longevity"
}advisor
{
"notes": "The model predicted anti_longevity with high confidence (0.88), but the ground truth is pro_longevity. The model's reasoning is mechanistically coherent in describing how Akt suppresses FOXO and activates TORC1, which are indeed established aging-related pathways. However, the model conflated \"reduced Akt activity extends lifespan\" with \"Akt is anti-longevity,\" which is the standard IIS narrative. In Drosophila, the GenAge classification of Akt as pro_longevity likely reflects that some level of Akt activity is required for normal survival/longevity, or that overexpression/activation studies in specific tissues (e.g., muscle or nervous system) can extend lifespan. The model's reasoning is one-sided and ignores the complexity that Akt can be pro-longevity in certain contexts in Drosophila. The model was confidently wrong about the direction of effect.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 3,
"ground_truth_questionable": true
}