acs-5
C. elegans
Long-chain-fatty-acid--CoA ligase
What the model saw
Gene: acs-5 Organism: Caenorhabditis elegans Known functions: Long-chain-fatty-acid--CoA ligase. arachidonate-CoA ligase activity. long-chain fatty acid-CoA ligase activity.
View unredacted entry
Long-chain-fatty-acid--CoA ligase. arachidonate-CoA ligase activity. long-chain fatty acid-CoA ligase activity.
Solver output
ACS-5 is a long-chain fatty acid-CoA ligase (acyl-CoA synthetase) that activates long-chain fatty acids, including arachidonate, by conjugating them to CoA. This is the committed first step in fatty acid beta-oxidation and lipid metabolism. In C. elegans, fatty acid activation and channeling into beta-oxidation is linked to mitochondrial energy metabolism and lipid homeostasis, both of which are central to nutrient-sensing pathways (e.g., AMPK, mTOR, insulin/IGF-1 signaling). Proper long-chain fatty acid metabolism supports mitochondrial function and prevents lipotoxicity; loss of acyl-CoA synthetase activity in worms has been associated with altered fat storage and reduced fitness. Additionally, arachidonate-CoA ligase activity connects to eicosanoid signaling, which can modulate inflammatory and stress responses relevant to aging. The net effect of normal ACS-5 function—facilitating productive fatty acid catabolism and lipid homeostasis—is predicted to be pro-longevity, though the confidence is moderate given the complexity of lipid signaling in aging.
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 predicted pro_longevity but the ground truth is anti_longevity. The model's reasoning about ACS-5 facilitating productive fatty acid catabolism and lipid homeostasis being beneficial is plausible in general terms, but it missed that acs-5 in C. elegans is actually anti-longevity (meaning its normal function shortens lifespan, or its loss extends lifespan). The model's mechanistic reasoning about beta-oxidation and lipid homeostasis being pro-longevity is not supported by the actual experimental data for this gene. The confidence of 0.55 is moderate but still wrong. The reasoning quality is low because it relied on generic pathway logic rather than specific knowledge about acs-5's role in C. elegans aging.
Raw API responses
solver
{
"reasoning": "ACS-5 is a long-chain fatty acid-CoA ligase (acyl-CoA synthetase) that activates long-chain fatty acids, including arachidonate, by conjugating them to CoA. This is the committed first step in fatty acid beta-oxidation and lipid metabolism. In C. elegans, fatty acid activation and channeling into beta-oxidation is linked to mitochondrial energy metabolism and lipid homeostasis, both of which are central to nutrient-sensing pathways (e.g., AMPK, mTOR, insulin/IGF-1 signaling). Proper long-chain fatty acid metabolism supports mitochondrial function and prevents lipotoxicity; loss of acyl-CoA synthetase activity in worms has been associated with altered fat storage and reduced fitness. Additionally, arachidonate-CoA ligase activity connects to eicosanoid signaling, which can modulate inflammatory and stress responses relevant to aging. The net effect of normal ACS-5 function—facilitating productive fatty acid catabolism and lipid homeostasis—is predicted to be pro-longevity, though the confidence is moderate given the complexity of lipid signaling in aging.",
"confidence": 0.55,
"key_pathways": [
"fatty acid beta-oxidation",
"lipid homeostasis / nutrient sensing",
"arachidonate/eicosanoid metabolism"
],
"mechanism_class": "deregulated_nutrient_sensing",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model predicted pro_longevity but the ground truth is anti_longevity. The model's reasoning about ACS-5 facilitating productive fatty acid catabolism and lipid homeostasis being beneficial is plausible in general terms, but it missed that acs-5 in C. elegans is actually anti-longevity (meaning its normal function shortens lifespan, or its loss extends lifespan). The model's mechanistic reasoning about beta-oxidation and lipid homeostasis being pro-longevity is not supported by the actual experimental data for this gene. The confidence of 0.55 is moderate but still wrong. The reasoning quality is low because it relied on generic pathway logic rather than specific knowledge about acs-5's role in C. elegans aging.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 2,
"ground_truth_questionable": false
}