spl-1
C. elegans
Sphingosine-1-phosphate lyase
What the model saw
Gene: spl-1 Organism: Caenorhabditis elegans Known functions: Sphingosine-1-phosphate lyase. carbon-carbon lyase activity. pyridoxal phosphate binding. sphinganine-1-phosphate aldolase activity.
View unredacted entry
Sphingosine-1-phosphate lyase. carbon-carbon lyase activity. pyridoxal phosphate binding. sphinganine-1-phosphate aldolase activity.
Solver output
Sphingosine-1-phosphate lyase (SPL-1) irreversibly degrades sphingosine-1-phosphate (S1P) by cleaving it into phosphoethanolamine and hexadecenal, thereby terminating S1P signaling. Elevated S1P levels promote cell survival and proliferation signals that can antagonize longevity pathways; by catabolizing S1P, SPL-1 reduces pro-survival/pro-growth sphingolipid signaling. In C. elegans, ceramide and sphingolipid metabolism intersect with the insulin/IGF-1 signaling (IIS) pathway and stress responses: higher ceramide (upstream of S1P) promotes DAF-16/FOXO nuclear localization and stress resistance, while S1P opposes this. Loss of S1P lyase activity leads to S1P accumulation, which suppresses DAF-16-dependent longevity programs. Additionally, S1P lyase activity generates phosphoethanolamine, feeding into phospholipid biosynthesis, and its pyridoxal phosphate-dependent mechanism links sphingolipid catabolism to one-carbon/vitamin B6 metabolism relevant to cellular homeostasis. Thus, normal SPL-1 function, by keeping S1P levels low and supporting ceramide-mediated pro-longevity signaling, is expected to be pro-longevity.
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 spl-1. The mechanistic reasoning is well-constructed and biologically plausible: SPL-1 degrades S1P, keeping S1P levels low, which supports ceramide-mediated pro-longevity signaling and DAF-16/FOXO activity. The connection to IIS pathway and stress responses is reasonable. The mechanism class "deregulated_nutrient_sensing" is a somewhat loose fit — sphingolipid signaling is more directly categorized under lipid metabolism or stress signaling — but the core mechanistic reasoning about the ceramide-S1P rheostat and its intersection with longevity pathways is sound. Confidence of 0.72 is appropriate given the complexity of sphingolipid biology.
Raw API responses
solver
{
"reasoning": "Sphingosine-1-phosphate lyase (SPL-1) irreversibly degrades sphingosine-1-phosphate (S1P) by cleaving it into phosphoethanolamine and hexadecenal, thereby terminating S1P signaling. Elevated S1P levels promote cell survival and proliferation signals that can antagonize longevity pathways; by catabolizing S1P, SPL-1 reduces pro-survival/pro-growth sphingolipid signaling. In C. elegans, ceramide and sphingolipid metabolism intersect with the insulin/IGF-1 signaling (IIS) pathway and stress responses: higher ceramide (upstream of S1P) promotes DAF-16/FOXO nuclear localization and stress resistance, while S1P opposes this. Loss of S1P lyase activity leads to S1P accumulation, which suppresses DAF-16-dependent longevity programs. Additionally, S1P lyase activity generates phosphoethanolamine, feeding into phospholipid biosynthesis, and its pyridoxal phosphate-dependent mechanism links sphingolipid catabolism to one-carbon/vitamin B6 metabolism relevant to cellular homeostasis. Thus, normal SPL-1 function, by keeping S1P levels low and supporting ceramide-mediated pro-longevity signaling, is expected to be pro-longevity.",
"confidence": 0.72,
"key_pathways": [
"sphingosine-1-phosphate catabolism / ceramide-S1P rheostat",
"insulin/IGF-1 signaling (DAF-2/DAF-16 axis)",
"sphingolipid-mediated stress response"
],
"mechanism_class": "deregulated_nutrient_sensing",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model correctly predicted pro_longevity for spl-1. The mechanistic reasoning is well-constructed and biologically plausible: SPL-1 degrades S1P, keeping S1P levels low, which supports ceramide-mediated pro-longevity signaling and DAF-16/FOXO activity. The connection to IIS pathway and stress responses is reasonable. The mechanism class \"deregulated_nutrient_sensing\" is a somewhat loose fit — sphingolipid signaling is more directly categorized under lipid metabolism or stress signaling — but the core mechanistic reasoning about the ceramide-S1P rheostat and its intersection with longevity pathways is sound. Confidence of 0.72 is appropriate given the complexity of sphingolipid biology.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 4,
"ground_truth_questionable": false
}