crtc-1
C. elegans
CREB-regulated transcription coactivator 1 homolog
What the model saw
Gene: crtc-1 Organism: Caenorhabditis elegans Known functions: CREB-regulated transcription coactivator 1 homolog. cAMP response element binding protein binding. transcription coactivator activity.
View unredacted entry
CREB-regulated transcription coactivator 1 homolog. cAMP response element binding protein binding. transcription coactivator activity.
Solver output
CRTC-1 is the C. elegans ortholog of the mammalian CREB-regulated transcription coactivator (CRTC), which acts as a coactivator of CREB-mediated transcription downstream of cAMP signaling. In C. elegans, crtc-1 functions in the CREB/CRH-1 transcriptional axis and is regulated by the energy-sensing kinase SIK (salt-inducible kinase), which itself is modulated by nutrient status and AMPK signaling. Loss of crtc-1 has been shown to extend lifespan in C. elegans, indicating that its normal activity is anti-longevity. Mechanistically, CRTC-1 promotes anabolic and growth-promoting transcriptional programs via CREB coactivation, opposing the pro-longevity effects of AMPK-mediated energy sensing. This places crtc-1 squarely within the deregulated nutrient-sensing hallmark, as its activity integrates cAMP/PKA and AMPK signals to modulate metabolic gene expression in ways that shorten lifespan when overactive.
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 anti_longevity for crtc-1 in C. elegans. The mechanistic reasoning is accurate and well-detailed: CRTC-1 is indeed a CREB coactivator regulated by the AMPK-SIK axis, and loss of crtc-1 extends lifespan in C. elegans. The mechanism class of "deregulated_nutrient_sensing" is appropriate given the AMPK-SIK-CRTC axis involvement. The key pathways identified are all relevant and correct. The confidence level of 0.72 is reasonable given the specificity of the knowledge required.
Raw API responses
solver
{
"reasoning": "CRTC-1 is the C. elegans ortholog of the mammalian CREB-regulated transcription coactivator (CRTC), which acts as a coactivator of CREB-mediated transcription downstream of cAMP signaling. In C. elegans, crtc-1 functions in the CREB/CRH-1 transcriptional axis and is regulated by the energy-sensing kinase SIK (salt-inducible kinase), which itself is modulated by nutrient status and AMPK signaling. Loss of crtc-1 has been shown to extend lifespan in C. elegans, indicating that its normal activity is anti-longevity. Mechanistically, CRTC-1 promotes anabolic and growth-promoting transcriptional programs via CREB coactivation, opposing the pro-longevity effects of AMPK-mediated energy sensing. This places crtc-1 squarely within the deregulated nutrient-sensing hallmark, as its activity integrates cAMP/PKA and AMPK signals to modulate metabolic gene expression in ways that shorten lifespan when overactive.",
"confidence": 0.72,
"key_pathways": [
"CREB/CRH-1 transcriptional coactivation",
"AMPK-SIK-CRTC nutrient sensing axis",
"cAMP/PKA signaling"
],
"mechanism_class": "deregulated_nutrient_sensing",
"longevity_influence": "anti_longevity"
}advisor
{
"notes": "The model correctly predicted anti_longevity for crtc-1 in C. elegans. The mechanistic reasoning is accurate and well-detailed: CRTC-1 is indeed a CREB coactivator regulated by the AMPK-SIK axis, and loss of crtc-1 extends lifespan in C. elegans. The mechanism class of \"deregulated_nutrient_sensing\" is appropriate given the AMPK-SIK-CRTC axis involvement. The key pathways identified are all relevant and correct. The confidence level of 0.72 is reasonable given the specificity of the knowledge required.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 5,
"ground_truth_questionable": false
}