aak-2
C. elegans
5'-AMP-activated protein kinase catalytic subunit alpha-2
What the model saw
Gene: aak-2 Organism: Caenorhabditis elegans Known functions: 5'-AMP-activated protein kinase catalytic subunit alpha-2. AMP-activated protein kinase activity. ATP binding. protein binding. protein kinase activity. protein serine kinase activity. protein serine/threonine kinase activity.
View unredacted entry
5'-AMP-activated protein kinase catalytic subunit alpha-2. AMP-activated protein kinase activity. ATP binding. protein binding. protein kinase activity. protein serine kinase activity. protein serine/threonine kinase activity.
Solver output
aak-2 encodes the catalytic alpha-2 subunit of AMP-activated protein kinase (AMPK) in C. elegans. AMPK is a master energy sensor that is activated under low-energy (high AMP:ATP) conditions and phosphorylates downstream targets to restore energy homeostasis. In the context of longevity, AMPK activation inhibits mTORC1 (via phosphorylation of RAPTOR and TSC2) and activates autophagy, directly opposing the pro-aging effects of deregulated nutrient sensing. In C. elegans, aak-2 is well-established to be required for lifespan extension under dietary restriction and in response to metformin, and it phosphorylates and activates DAF-16/FOXO transcription factor. Loss of aak-2 shortens lifespan, while its activation extends it, firmly placing it in the pro-longevity category through the AMPK–mTOR–DAF-16 nutrient-sensing axis.
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 aak-2 as pro_longevity with very high confidence (0.95). The mechanistic reasoning is accurate and detailed: AMPK (aak-2) is indeed a master energy sensor that promotes longevity in C. elegans through inhibition of mTORC1, activation of autophagy, and phosphorylation/activation of DAF-16/FOXO. The model correctly notes that loss of aak-2 shortens lifespan and that it is required for dietary restriction-mediated lifespan extension. The mechanism class "deregulated_nutrient_sensing" is appropriate. All key pathways cited are well-supported by the literature.
Raw API responses
solver
{
"reasoning": "aak-2 encodes the catalytic alpha-2 subunit of AMP-activated protein kinase (AMPK) in C. elegans. AMPK is a master energy sensor that is activated under low-energy (high AMP:ATP) conditions and phosphorylates downstream targets to restore energy homeostasis. In the context of longevity, AMPK activation inhibits mTORC1 (via phosphorylation of RAPTOR and TSC2) and activates autophagy, directly opposing the pro-aging effects of deregulated nutrient sensing. In C. elegans, aak-2 is well-established to be required for lifespan extension under dietary restriction and in response to metformin, and it phosphorylates and activates DAF-16/FOXO transcription factor. Loss of aak-2 shortens lifespan, while its activation extends it, firmly placing it in the pro-longevity category through the AMPK–mTOR–DAF-16 nutrient-sensing axis.",
"confidence": 0.95,
"key_pathways": [
"AMPK-mTOR nutrient sensing",
"DAF-16/FOXO transcription factor activation",
"dietary restriction longevity pathway"
],
"mechanism_class": "deregulated_nutrient_sensing",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model correctly identified aak-2 as pro_longevity with very high confidence (0.95). The mechanistic reasoning is accurate and detailed: AMPK (aak-2) is indeed a master energy sensor that promotes longevity in C. elegans through inhibition of mTORC1, activation of autophagy, and phosphorylation/activation of DAF-16/FOXO. The model correctly notes that loss of aak-2 shortens lifespan and that it is required for dietary restriction-mediated lifespan extension. The mechanism class \"deregulated_nutrient_sensing\" is appropriate. All key pathways cited are well-supported by the literature.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 5,
"ground_truth_questionable": false
}