sptl-1
C. elegans
Serine palmitoyltransferase 1
What the model saw
Gene: sptl-1 Organism: Caenorhabditis elegans Known functions: Serine palmitoyltransferase 1. pyridoxal phosphate binding. serine C-palmitoyltransferase activity.
View unredacted entry
Serine palmitoyltransferase 1. pyridoxal phosphate binding. serine C-palmitoyltransferase activity.
Solver output
sptl-1 encodes the large subunit of serine palmitoyltransferase (SPT), the rate-limiting enzyme catalyzing the first and committed step of de novo sphingolipid biosynthesis: the condensation of L-serine and palmitoyl-CoA to form 3-ketodihydrosphingosine, using pyridoxal phosphate as a cofactor. Elevated sphingolipid levels, particularly ceramide, are associated with cellular stress, growth arrest, and pro-apoptotic signaling. In C. elegans, increased ceramide and complex sphingolipid synthesis has been linked to reduced lifespan, while reduction of SPT activity extends lifespan in multiple model organisms. Sphingolipids also modulate insulin/IGF-1 signaling and nutrient-sensing pathways; excess ceramide antagonizes PI3K/AKT signaling downstream of DAF-2, but the net organismal effect of SPT activity is pro-aging due to ceramide-driven lipotoxicity and cellular senescence-like responses. Loss-of-function or reduction of sptl-1 activity is therefore expected to be pro-longevity, meaning the normal function of sptl-1 opposes 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 anti_longevity for sptl-1. The mechanistic reasoning is sound: sptl-1 encodes serine palmitoyltransferase, the rate-limiting enzyme in de novo sphingolipid biosynthesis, and elevated ceramide/sphingolipid levels are pro-aging. The model correctly concludes that loss-of-function of sptl-1 extends lifespan, making the gene anti-longevity. The reasoning about ceramide-driven lipotoxicity and modulation of insulin/IGF-1 signaling is biologically plausible. The confidence of 0.72 is appropriate. Minor note: the model's claim that "reduction of SPT activity extends lifespan in multiple model organisms" is stated with some confidence but is well-supported in the literature for C. elegans specifically.
Raw API responses
solver
{
"reasoning": "sptl-1 encodes the large subunit of serine palmitoyltransferase (SPT), the rate-limiting enzyme catalyzing the first and committed step of de novo sphingolipid biosynthesis: the condensation of L-serine and palmitoyl-CoA to form 3-ketodihydrosphingosine, using pyridoxal phosphate as a cofactor. Elevated sphingolipid levels, particularly ceramide, are associated with cellular stress, growth arrest, and pro-apoptotic signaling. In C. elegans, increased ceramide and complex sphingolipid synthesis has been linked to reduced lifespan, while reduction of SPT activity extends lifespan in multiple model organisms. Sphingolipids also modulate insulin/IGF-1 signaling and nutrient-sensing pathways; excess ceramide antagonizes PI3K/AKT signaling downstream of DAF-2, but the net organismal effect of SPT activity is pro-aging due to ceramide-driven lipotoxicity and cellular senescence-like responses. Loss-of-function or reduction of sptl-1 activity is therefore expected to be pro-longevity, meaning the normal function of sptl-1 opposes longevity.",
"confidence": 0.72,
"key_pathways": [
"de novo sphingolipid/ceramide biosynthesis",
"insulin/IGF-1 signaling (DAF-2/DAF-16 axis)",
"lipotoxicity and cellular stress signaling"
],
"mechanism_class": "deregulated_nutrient_sensing",
"longevity_influence": "anti_longevity"
}advisor
{
"notes": "The model correctly predicted anti_longevity for sptl-1. The mechanistic reasoning is sound: sptl-1 encodes serine palmitoyltransferase, the rate-limiting enzyme in de novo sphingolipid biosynthesis, and elevated ceramide/sphingolipid levels are pro-aging. The model correctly concludes that loss-of-function of sptl-1 extends lifespan, making the gene anti-longevity. The reasoning about ceramide-driven lipotoxicity and modulation of insulin/IGF-1 signaling is biologically plausible. The confidence of 0.72 is appropriate. Minor note: the model's claim that \"reduction of SPT activity extends lifespan in multiple model organisms\" is stated with some confidence but is well-supported in the literature for C. elegans specifically.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 4,
"ground_truth_questionable": false
}