asm-3
C. elegans
Putative sphingomyelin phosphodiesterase asm-3;Sphingomyelin phosphodiesterase
What the model saw
Gene: asm-3 Organism: Caenorhabditis elegans Known functions: Putative sphingomyelin phosphodiesterase asm-3;Sphingomyelin phosphodiesterase. acid sphingomyelin phosphodiesterase activity. hydrolase activity. sphingomyelin phosphodiesterase activity.
View unredacted entry
Putative sphingomyelin phosphodiesterase asm-3;Sphingomyelin phosphodiesterase. acid sphingomyelin phosphodiesterase activity. hydrolase activity. sphingomyelin phosphodiesterase activity.
Solver output
asm-3 encodes an acid sphingomyelinase (aSMase) that hydrolyzes sphingomyelin into ceramide and phosphocholine. Ceramide is a pro-apoptotic and pro-senescent lipid second messenger; elevated ceramide levels promote cellular stress responses, apoptosis, and inflammation. In C. elegans, increased ceramide generation via sphingomyelinase activity has been linked to reduced stress resistance and shortened lifespan, as ceramide antagonizes pro-survival insulin/IGF-1 signaling (DAF-2/DAF-16 pathway) and promotes stress-induced cell death. The normal function of asm-3 thus generates ceramide, which acts as an anti-longevity signal by dampening DAF-16-mediated transcription of stress-resistance and longevity genes. Loss of asm-3 function would be expected to reduce ceramide accumulation and extend lifespan, consistent with an anti-longevity role for the wild-type gene.
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 asm-3. The mechanistic reasoning is sound: asm-3 encodes an acid sphingomyelinase that generates ceramide, which is a pro-apoptotic/pro-senescent lipid that antagonizes pro-survival signaling. The connection to DAF-2/DAF-16 pathway is plausible and consistent with known ceramide biology in C. elegans. The mechanism class "altered_intercellular_communication" is somewhat debatable (ceramide signaling is more intracellular than intercellular), but the core reasoning about ceramide as an anti-longevity signal is correct. Confidence of 0.72 is appropriate given the specificity of the gene.
Raw API responses
solver
{
"reasoning": "asm-3 encodes an acid sphingomyelinase (aSMase) that hydrolyzes sphingomyelin into ceramide and phosphocholine. Ceramide is a pro-apoptotic and pro-senescent lipid second messenger; elevated ceramide levels promote cellular stress responses, apoptosis, and inflammation. In C. elegans, increased ceramide generation via sphingomyelinase activity has been linked to reduced stress resistance and shortened lifespan, as ceramide antagonizes pro-survival insulin/IGF-1 signaling (DAF-2/DAF-16 pathway) and promotes stress-induced cell death. The normal function of asm-3 thus generates ceramide, which acts as an anti-longevity signal by dampening DAF-16-mediated transcription of stress-resistance and longevity genes. Loss of asm-3 function would be expected to reduce ceramide accumulation and extend lifespan, consistent with an anti-longevity role for the wild-type gene.",
"confidence": 0.72,
"key_pathways": [
"sphingomyelin/ceramide signaling",
"insulin/IGF-1 signaling (DAF-2/DAF-16)",
"stress-induced apoptosis"
],
"mechanism_class": "altered_intercellular_communication",
"longevity_influence": "anti_longevity"
}advisor
{
"notes": "The model correctly predicted anti_longevity for asm-3. The mechanistic reasoning is sound: asm-3 encodes an acid sphingomyelinase that generates ceramide, which is a pro-apoptotic/pro-senescent lipid that antagonizes pro-survival signaling. The connection to DAF-2/DAF-16 pathway is plausible and consistent with known ceramide biology in C. elegans. The mechanism class \"altered_intercellular_communication\" is somewhat debatable (ceramide signaling is more intracellular than intercellular), but the core reasoning about ceramide as an anti-longevity signal is correct. Confidence of 0.72 is appropriate given the specificity of the gene.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 4,
"ground_truth_questionable": false
}