AMPKalpha
D. melanogaster
AMP-activated protein kinase alpha subunit
What the model saw
Gene: AMPKalpha Organism: Drosophila melanogaster Known functions: AMP-activated protein kinase alpha subunit. AMP-activated protein kinase activity. ATP binding. nucleotide binding. protein kinase activity. protein serine/threonine kinase activity.
View unredacted entry
AMP-activated protein kinase alpha subunit. AMP-activated protein kinase activity. ATP binding. nucleotide binding. protein kinase activity. protein serine/threonine kinase activity.
Solver output
AMPKα is the catalytic subunit of AMP-activated protein kinase, a master energy sensor that is activated when cellular AMP:ATP ratios rise (low energy states). In Drosophila, AMPK phosphorylates and inhibits anabolic targets such as TOR complex 1 (via TSC2 and Raptor phosphorylation) and activates catabolic processes including autophagy (via ULK1/Atg1 phosphorylation), fatty acid oxidation, and mitochondrial biogenesis. This activity directly opposes the pro-aging effects of hyperactive TOR/insulin-IGF signaling, a well-established longevity axis. Genetic activation of AMPK in Drosophila has been shown to extend lifespan, while loss of AMPKα shortens it, consistent with its role as a nutrient-sensing longevity effector. Additionally, AMPK promotes mitochondrial quality control and suppresses cellular senescence-associated metabolic dysfunction, further reinforcing its pro-longevity role.
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 pro_longevity for AMPKalpha in Drosophila with high confidence (0.93). The mechanistic reasoning is thorough and accurate: AMPK as an energy sensor, its inhibition of TOR via TSC2/Raptor phosphorylation, activation of autophagy via ULK1/Atg1, and antagonism of insulin-IGF signaling are all well-established mechanisms. The model correctly notes that genetic activation extends lifespan while loss shortens it in Drosophila. The mechanism class of "deregulated_nutrient_sensing" is appropriate. Overall, this is an excellent prediction with solid mechanistic reasoning.
Raw API responses
solver
{
"reasoning": "AMPKα is the catalytic subunit of AMP-activated protein kinase, a master energy sensor that is activated when cellular AMP:ATP ratios rise (low energy states). In Drosophila, AMPK phosphorylates and inhibits anabolic targets such as TOR complex 1 (via TSC2 and Raptor phosphorylation) and activates catabolic processes including autophagy (via ULK1/Atg1 phosphorylation), fatty acid oxidation, and mitochondrial biogenesis. This activity directly opposes the pro-aging effects of hyperactive TOR/insulin-IGF signaling, a well-established longevity axis. Genetic activation of AMPK in Drosophila has been shown to extend lifespan, while loss of AMPKα shortens it, consistent with its role as a nutrient-sensing longevity effector. Additionally, AMPK promotes mitochondrial quality control and suppresses cellular senescence-associated metabolic dysfunction, further reinforcing its pro-longevity role.",
"confidence": 0.93,
"key_pathways": [
"AMPK-TOR nutrient sensing axis",
"Autophagy induction via ULK1/Atg1 phosphorylation",
"Insulin-IGF signaling antagonism"
],
"mechanism_class": "deregulated_nutrient_sensing",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model correctly predicted pro_longevity for AMPKalpha in Drosophila with high confidence (0.93). The mechanistic reasoning is thorough and accurate: AMPK as an energy sensor, its inhibition of TOR via TSC2/Raptor phosphorylation, activation of autophagy via ULK1/Atg1, and antagonism of insulin-IGF signaling are all well-established mechanisms. The model correctly notes that genetic activation extends lifespan while loss shortens it in Drosophila. The mechanism class of \"deregulated_nutrient_sensing\" is appropriate. Overall, this is an excellent prediction with solid mechanistic reasoning.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 5,
"ground_truth_questionable": false
}