sams-3
C. elegans
putative S-adenosylmethionine synthase 3
What the model saw
Gene: sams-3 Organism: Caenorhabditis elegans Known functions: putative S-adenosylmethionine synthase 3. ATP binding. methionine adenosyltransferase activity. protein binding.
View unredacted entry
putative S-adenosylmethionine synthase 3. ATP binding. methionine adenosyltransferase activity. protein binding.
Solver output
sams-3 encodes an S-adenosylmethionine (SAM) synthase, which catalyzes the conversion of methionine and ATP into SAM — the universal methyl donor for DNA, RNA, histone, and protein methylation reactions. Elevated SAM production supports increased methylation of histones (e.g., H3K4me3 via SET-2/MLL complex) and other substrates, which has been shown in C. elegans to promote aging; conversely, reduction of SAM synthetase activity (e.g., sams-1 RNAi) extends lifespan by reducing methyl donor availability and altering one-carbon metabolism. The methionine restriction paradigm, well-established in multiple organisms including C. elegans, extends lifespan partly by limiting SAM levels and downstream methylation flux. Additionally, SAM is a key node connecting nutrient sensing (methionine/one-carbon metabolism) to epigenetic regulation, and its overproduction drives pro-aging epigenetic states. Thus, normal sams-3 function, by sustaining or elevating SAM synthesis, is predicted to be anti-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 sams-3. The mechanistic reasoning is well-grounded: SAM synthases produce the universal methyl donor SAM, and reduction of SAM synthetase activity (as seen with sams-1 RNAi) extends lifespan in C. elegans. The model correctly draws the parallel to sams-3 and connects it to epigenetic regulation via histone methylation and methionine restriction pathways. The reasoning is solid and consistent with the known biology of SAM metabolism in C. elegans aging. The confidence level of 0.72 is appropriate given that sams-3 is less studied than sams-1. Minor note: the model could have been more specific about whether sams-3 knockdown specifically has been shown to extend lifespan, or whether this is inferred from the sams-1 analogy, but the overall reasoning is sound.
Raw API responses
solver
{
"reasoning": "sams-3 encodes an S-adenosylmethionine (SAM) synthase, which catalyzes the conversion of methionine and ATP into SAM — the universal methyl donor for DNA, RNA, histone, and protein methylation reactions. Elevated SAM production supports increased methylation of histones (e.g., H3K4me3 via SET-2/MLL complex) and other substrates, which has been shown in C. elegans to promote aging; conversely, reduction of SAM synthetase activity (e.g., sams-1 RNAi) extends lifespan by reducing methyl donor availability and altering one-carbon metabolism. The methionine restriction paradigm, well-established in multiple organisms including C. elegans, extends lifespan partly by limiting SAM levels and downstream methylation flux. Additionally, SAM is a key node connecting nutrient sensing (methionine/one-carbon metabolism) to epigenetic regulation, and its overproduction drives pro-aging epigenetic states. Thus, normal sams-3 function, by sustaining or elevating SAM synthesis, is predicted to be anti-longevity.",
"confidence": 0.72,
"key_pathways": [
"S-adenosylmethionine (SAM) biosynthesis / one-carbon metabolism",
"Histone methylation (H3K4me3 via SAM-dependent methyltransferases)",
"Methionine restriction longevity pathway"
],
"mechanism_class": "epigenetic_alterations",
"longevity_influence": "anti_longevity"
}advisor
{
"notes": "The model correctly predicted anti_longevity for sams-3. The mechanistic reasoning is well-grounded: SAM synthases produce the universal methyl donor SAM, and reduction of SAM synthetase activity (as seen with sams-1 RNAi) extends lifespan in C. elegans. The model correctly draws the parallel to sams-3 and connects it to epigenetic regulation via histone methylation and methionine restriction pathways. The reasoning is solid and consistent with the known biology of SAM metabolism in C. elegans aging. The confidence level of 0.72 is appropriate given that sams-3 is less studied than sams-1. Minor note: the model could have been more specific about whether sams-3 knockdown specifically has been shown to extend lifespan, or whether this is inferred from the sams-1 analogy, but the overall reasoning is sound.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 4,
"ground_truth_questionable": false
}