lipl-4
C. elegans
Lipase lipl-4
What the model saw
Gene: lipl-4 Organism: Caenorhabditis elegans Known functions: Lipase lipl-4. hydrolase activity, acting on ester bonds. lipase activity. triacylglycerol lipase activity.
View unredacted entry
Lipase lipl-4. hydrolase activity, acting on ester bonds. lipase activity. triacylglycerol lipase activity.
Solver output
LIPL-4 is a lysosomal acid lipase in C. elegans that hydrolyzes triacylglycerols, releasing fatty acids that act as signaling molecules. Overexpression of lipl-4 is well-established to extend lifespan in C. elegans by activating a lipid-to-nuclear signaling axis: the released fatty acids (particularly oleoylethanolamide) bind to the nuclear receptor NHR-80/HNF4 and activate transcription factors including MXL-3 and HLH-30/TFEB, promoting autophagy and lipid catabolism. This pathway intersects with the TORC1/autophagy nutrient-sensing axis, as lysosomal lipase activity is upregulated under dietary restriction and in long-lived daf-2 insulin/IGF-1 receptor mutants. The triacylglycerol lipase activity of LIPL-4 thus serves as a key node linking lipid metabolism to longevity-promoting transcriptional programs.
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 lipl-4 in C. elegans with high confidence (0.85). The mechanistic reasoning is excellent and accurate: LIPL-4 is indeed a lysosomal acid lipase whose overexpression extends lifespan via lipid-to-nuclear signaling involving oleoylethanolamide, NHR-80/HNF4, HLH-30/TFEB, and connections to autophagy and dietary restriction pathways. The key pathways identified are all well-supported in the literature. This is a well-known longevity gene in C. elegans and the model demonstrated deep, accurate knowledge of the underlying biology.
Raw API responses
solver
{
"reasoning": "LIPL-4 is a lysosomal acid lipase in C. elegans that hydrolyzes triacylglycerols, releasing fatty acids that act as signaling molecules. Overexpression of lipl-4 is well-established to extend lifespan in C. elegans by activating a lipid-to-nuclear signaling axis: the released fatty acids (particularly oleoylethanolamide) bind to the nuclear receptor NHR-80/HNF4 and activate transcription factors including MXL-3 and HLH-30/TFEB, promoting autophagy and lipid catabolism. This pathway intersects with the TORC1/autophagy nutrient-sensing axis, as lysosomal lipase activity is upregulated under dietary restriction and in long-lived daf-2 insulin/IGF-1 receptor mutants. The triacylglycerol lipase activity of LIPL-4 thus serves as a key node linking lipid metabolism to longevity-promoting transcriptional programs.",
"confidence": 0.85,
"key_pathways": [
"Lysosomal lipid signaling / NHR-80 nuclear receptor axis",
"Autophagy / HLH-30 (TFEB) activation",
"Dietary restriction and TOR nutrient-sensing pathway"
],
"mechanism_class": "deregulated_nutrient_sensing",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model correctly predicted pro_longevity for lipl-4 in C. elegans with high confidence (0.85). The mechanistic reasoning is excellent and accurate: LIPL-4 is indeed a lysosomal acid lipase whose overexpression extends lifespan via lipid-to-nuclear signaling involving oleoylethanolamide, NHR-80/HNF4, HLH-30/TFEB, and connections to autophagy and dietary restriction pathways. The key pathways identified are all well-supported in the literature. This is a well-known longevity gene in C. elegans and the model demonstrated deep, accurate knowledge of the underlying biology.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 5,
"ground_truth_questionable": false
}