Adcy5
M. musculus
adenylate cyclase 5
What the model saw
Gene: Adcy5 Organism: Mus musculus Known functions: adenylate cyclase 5. adenylate cyclase type 5. adenylate cyclase activity. adenylate cyclase binding. calcium- and calmodulin-responsive adenylate cyclase activity. phosphorus-oxygen lyase activity. protein binding. scaffold protein binding.
View unredacted entry
adenylate cyclase 5. adenylate cyclase type 5. adenylate cyclase activity. adenylate cyclase binding. calcium- and calmodulin-responsive adenylate cyclase activity. phosphorus-oxygen lyase activity. protein binding. scaffold protein binding.
Solver output
Adenylate cyclase 5 (ADCY5) catalyzes the conversion of ATP to cAMP, a second messenger that activates PKA signaling downstream of G-protein-coupled receptors. Elevated cAMP/PKA activity promotes catecholamine and glucagon signaling, which antagonizes insulin sensitivity and activates pro-aging nutrient-sensing cascades. Critically, Adcy5 knockout mice have been shown to live significantly longer than wild-type controls, with improved mitochondrial function and reduced oxidative stress, demonstrating that the normal (pro-cAMP) function of ADCY5 is detrimental to longevity. The calcium/calmodulin-responsive adenylate cyclase activity of ADCY5 also links it to stress-response pathways in cardiac and neuronal tissues where chronic activation accelerates cellular aging. Thus, the normal enzymatic function of ADCY5 — sustained cAMP production — opposes longevity by over-activating PKA-dependent nutrient-sensing and stress pathways.
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 identifies Adcy5 as anti_longevity with high confidence (0.82). The mechanistic reasoning is largely correct: Adcy5 knockout mice do live longer, and the cAMP/PKA pathway is central to the longevity effect. The model correctly notes that ADCY5's normal function (cAMP production) is detrimental to longevity. The mechanism class "deregulated_nutrient_sensing" is a reasonable categorization, though the primary published mechanism for Adcy5 KO longevity involves reduced oxidative stress and improved mitochondrial function rather than strictly nutrient sensing. The mention of glucagon-cAMP axis antagonizing insulin sensitivity is a reasonable but somewhat speculative extension. Overall, the core answer and mechanism are correct, with minor imprecision in the mechanistic framing.
Raw API responses
solver
{
"reasoning": "Adenylate cyclase 5 (ADCY5) catalyzes the conversion of ATP to cAMP, a second messenger that activates PKA signaling downstream of G-protein-coupled receptors. Elevated cAMP/PKA activity promotes catecholamine and glucagon signaling, which antagonizes insulin sensitivity and activates pro-aging nutrient-sensing cascades. Critically, Adcy5 knockout mice have been shown to live significantly longer than wild-type controls, with improved mitochondrial function and reduced oxidative stress, demonstrating that the normal (pro-cAMP) function of ADCY5 is detrimental to longevity. The calcium/calmodulin-responsive adenylate cyclase activity of ADCY5 also links it to stress-response pathways in cardiac and neuronal tissues where chronic activation accelerates cellular aging. Thus, the normal enzymatic function of ADCY5 — sustained cAMP production — opposes longevity by over-activating PKA-dependent nutrient-sensing and stress pathways.",
"confidence": 0.82,
"key_pathways": [
"cAMP-PKA signaling",
"G-protein coupled receptor / adenylate cyclase cascade",
"insulin/IGF-1 antagonism via glucagon-cAMP axis"
],
"mechanism_class": "deregulated_nutrient_sensing",
"longevity_influence": "anti_longevity"
}advisor
{
"notes": "The model correctly identifies Adcy5 as anti_longevity with high confidence (0.82). The mechanistic reasoning is largely correct: Adcy5 knockout mice do live longer, and the cAMP/PKA pathway is central to the longevity effect. The model correctly notes that ADCY5's normal function (cAMP production) is detrimental to longevity. The mechanism class \"deregulated_nutrient_sensing\" is a reasonable categorization, though the primary published mechanism for Adcy5 KO longevity involves reduced oxidative stress and improved mitochondrial function rather than strictly nutrient sensing. The mention of glucagon-cAMP axis antagonizing insulin sensitivity is a reasonable but somewhat speculative extension. Overall, the core answer and mechanism are correct, with minor imprecision in the mechanistic framing.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 4,
"ground_truth_questionable": false
}