Akt1
M. musculus
Akt serine/threonine kinase 1
What the model saw
Gene: Akt1 Organism: Mus musculus Known functions: Akt serine/threonine kinase 1. RAC-alpha serine/threonine-protein kinase. 14-3-3 protein binding. ATP binding. GTPase activating protein binding. TORC2 complex binding. calmodulin binding. enzyme binding. identical protein binding. kinase activity. kinase binding. nitric-oxide synthase regulator activity. phosphatidylinositol-3,4,5-trisphosphate binding. phosphatidylinositol-3,4-bisphosphate binding. potassium channel activator activity. protein binding. protein homodimerization activity. protein kinase C binding. protein kinase activity. protein kinase binding. protein phosphatase 2A binding. protein serine kinase activity. protein serine/threonine kinase activity. protein serine/threonine kinase binding. protein serine/threonine kinase inhibitor activity. protein serine/threonine/tyrosine kinase activity.
View unredacted entry
Akt serine/threonine kinase 1. RAC-alpha serine/threonine-protein kinase. 14-3-3 protein binding. ATP binding. GTPase activating protein binding. TORC2 complex binding. calmodulin binding. enzyme binding. identical protein binding. kinase activity. kinase binding. nitric-oxide synthase regulator activity. phosphatidylinositol-3,4,5-trisphosphate binding. phosphatidylinositol-3,4-bisphosphate binding. potassium channel activator activity. protein binding. protein homodimerization activity. protein kinase C binding. protein kinase activity. protein kinase binding. protein phosphatase 2A binding. protein serine kinase activity. protein serine/threonine kinase activity. protein serine/threonine kinase binding. protein serine/threonine kinase inhibitor activity. protein serine/threonine/tyrosine kinase activity.
Solver output
Akt1 is the central kinase of the PI3K/Akt/mTOR signaling axis, activated downstream of insulin/IGF-1 receptor signaling via phosphatidylinositol-3,4,5-trisphosphate (PIP3) binding at the plasma membrane. Elevated Akt1 activity promotes mTORC1 activation (via TSC1/2 phosphorylation and PRAS40 inhibition), suppressing autophagy and driving anabolic metabolism — both hallmarks of accelerated aging. Reduced insulin/IGF-1 signaling through this pathway is one of the most conserved pro-longevity interventions across model organisms, and Akt1 knockout mice show extended lifespan in some studies. Akt1 also phosphorylates and inhibits FOXO transcription factors, which are key mediators of stress resistance and longevity. The PIP3-binding and protein serine/threonine kinase activity annotations confirm its role as the primary effector of nutrient/growth factor sensing that, when overactive, shortens lifespan.
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 Akt1 as anti_longevity with high confidence (0.82). The mechanistic reasoning is excellent and accurate: Akt1 is indeed the central kinase of the PI3K/Akt/mTOR axis downstream of insulin/IGF-1 signaling, and reduced activity of this pathway is a well-established pro-longevity intervention. The model correctly identifies FOXO inhibition, mTORC1 activation, and suppression of autophagy as key mechanisms. The mention of Akt1 knockout mice showing extended lifespan is consistent with the anti_longevity classification. All key pathways identified are relevant and accurate.
Raw API responses
solver
{
"reasoning": "Akt1 is the central kinase of the PI3K/Akt/mTOR signaling axis, activated downstream of insulin/IGF-1 receptor signaling via phosphatidylinositol-3,4,5-trisphosphate (PIP3) binding at the plasma membrane. Elevated Akt1 activity promotes mTORC1 activation (via TSC1/2 phosphorylation and PRAS40 inhibition), suppressing autophagy and driving anabolic metabolism — both hallmarks of accelerated aging. Reduced insulin/IGF-1 signaling through this pathway is one of the most conserved pro-longevity interventions across model organisms, and Akt1 knockout mice show extended lifespan in some studies. Akt1 also phosphorylates and inhibits FOXO transcription factors, which are key mediators of stress resistance and longevity. The PIP3-binding and protein serine/threonine kinase activity annotations confirm its role as the primary effector of nutrient/growth factor sensing that, when overactive, shortens lifespan.",
"confidence": 0.82,
"key_pathways": [
"PI3K/Akt/mTOR nutrient sensing",
"Insulin/IGF-1 signaling (IIS) pathway",
"FOXO transcription factor inhibition"
],
"mechanism_class": "deregulated_nutrient_sensing",
"longevity_influence": "anti_longevity"
}advisor
{
"notes": "The model correctly predicted Akt1 as anti_longevity with high confidence (0.82). The mechanistic reasoning is excellent and accurate: Akt1 is indeed the central kinase of the PI3K/Akt/mTOR axis downstream of insulin/IGF-1 signaling, and reduced activity of this pathway is a well-established pro-longevity intervention. The model correctly identifies FOXO inhibition, mTORC1 activation, and suppression of autophagy as key mechanisms. The mention of Akt1 knockout mice showing extended lifespan is consistent with the anti_longevity classification. All key pathways identified are relevant and accurate.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 5,
"ground_truth_questionable": false
}