Akt2
M. musculus
Akt serine/threonine kinase 2
What the model saw
Gene: Akt2 Organism: Mus musculus Known functions: Akt serine/threonine kinase 2. RAC-beta serine/threonine-protein kinase. ATP binding. molecular function activator activity. protein binding. protein kinase C binding. protein kinase activity. protein serine kinase activity. protein serine/threonine kinase activity.
View unredacted entry
Akt serine/threonine kinase 2. RAC-beta serine/threonine-protein kinase. ATP binding. molecular function activator activity. protein binding. protein kinase C binding. protein kinase activity. protein serine kinase activity. protein serine/threonine kinase activity.
Solver output
Akt2 (RAC-beta serine/threonine-protein kinase) is a central effector of the PI3K/AKT/mTOR signaling axis, which is a core component of the insulin/IGF-1 signaling (IIS) pathway. Activation of Akt2 phosphorylates and inhibits FOXO transcription factors and activates mTORC1, both of which suppress autophagy and stress resistance programs associated with longevity. In mice, reduced IIS/mTOR signaling (e.g., in Ames dwarf, Snell dwarf, or mTOR-hypomorphic models) consistently extends lifespan, indicating that normal Akt activity opposes longevity. Akt2 specifically plays a dominant role in insulin-mediated glucose metabolism; its sustained activation promotes anabolic, growth-promoting states that are anti-longevity. While Akt2 knockout mice show improved insulin sensitivity in some contexts, the isoform's primary molecular function as a serine/threonine kinase activator within the IIS pathway places it firmly in the pro-growth, anti-longevity category.
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 predicted Akt2 as anti_longevity, matching the ground truth. The mechanistic reasoning is sound - Akt2 is indeed a key effector of the PI3K/AKT/mTOR and insulin/IGF-1 signaling pathways, and its activity promotes anabolic, growth-promoting states that are generally anti-longevity. The model correctly identifies FOXO inhibition and mTORC1 activation as key downstream effects. The reasoning is slightly imprecise in one area: Akt2 knockout mice actually show insulin resistance (not improved insulin sensitivity) in some metabolic contexts, though this doesn't affect the final classification. The model's confidence of 0.72 is appropriate given the complexity of Akt isoform-specific effects. Overall, solid reasoning leading to the correct answer.
Raw API responses
solver
{
"reasoning": "Akt2 (RAC-beta serine/threonine-protein kinase) is a central effector of the PI3K/AKT/mTOR signaling axis, which is a core component of the insulin/IGF-1 signaling (IIS) pathway. Activation of Akt2 phosphorylates and inhibits FOXO transcription factors and activates mTORC1, both of which suppress autophagy and stress resistance programs associated with longevity. In mice, reduced IIS/mTOR signaling (e.g., in Ames dwarf, Snell dwarf, or mTOR-hypomorphic models) consistently extends lifespan, indicating that normal Akt activity opposes longevity. Akt2 specifically plays a dominant role in insulin-mediated glucose metabolism; its sustained activation promotes anabolic, growth-promoting states that are anti-longevity. While Akt2 knockout mice show improved insulin sensitivity in some contexts, the isoform's primary molecular function as a serine/threonine kinase activator within the IIS pathway places it firmly in the pro-growth, anti-longevity category.",
"confidence": 0.72,
"key_pathways": [
"PI3K/AKT/mTOR nutrient sensing pathway",
"Insulin/IGF-1 signaling (IIS) and FOXO inhibition",
"mTORC1 activation and autophagy suppression"
],
"mechanism_class": "deregulated_nutrient_sensing",
"longevity_influence": "anti_longevity"
}advisor
{
"notes": "The model correctly predicted Akt2 as anti_longevity, matching the ground truth. The mechanistic reasoning is sound - Akt2 is indeed a key effector of the PI3K/AKT/mTOR and insulin/IGF-1 signaling pathways, and its activity promotes anabolic, growth-promoting states that are generally anti-longevity. The model correctly identifies FOXO inhibition and mTORC1 activation as key downstream effects. The reasoning is slightly imprecise in one area: Akt2 knockout mice actually show insulin resistance (not improved insulin sensitivity) in some metabolic contexts, though this doesn't affect the final classification. The model's confidence of 0.72 is appropriate given the complexity of Akt isoform-specific effects. Overall, solid reasoning leading to the correct answer.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 4,
"ground_truth_questionable": false
}