let-363
C. elegans
Target of rapamycin homolog
What the model saw
Gene: let-363 Organism: Caenorhabditis elegans Known functions: Target of rapamycin homolog. kinase activity. protein serine kinase activity. protein serine/threonine kinase activity. protein-containing complex binding.
View unredacted entry
Target of rapamycin homolog. kinase activity. protein serine kinase activity. protein serine/threonine kinase activity. protein-containing complex binding.
Solver output
let-363 encodes the C. elegans ortholog of TOR (Target of Rapamycin), a central serine/threonine kinase that integrates nutrient, energy, and growth factor signals. In its normal active state, TOR (as part of TORC1) phosphorylates downstream effectors such as S6 kinase (rsks-1) and 4E-BP (ifg-1/ife-4), promoting anabolic processes including protein synthesis and suppressing autophagy. This active nutrient-sensing state is well-established to shorten lifespan in C. elegans; genetic reduction or RNAi knockdown of let-363 robustly extends lifespan. Thus, the normal kinase function of let-363 opposes longevity by driving growth and suppressing stress-response and autophagic pathways that promote survival.
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 identified let-363 as anti_longevity with high confidence (0.95). The mechanistic reasoning is excellent: it correctly identifies let-363 as the C. elegans TOR ortholog, explains how active TOR promotes anabolic processes (via S6K/rsks-1 and 4E-BP phosphorylation), suppresses autophagy, and correctly states that RNAi knockdown of let-363 extends lifespan. The mechanism class of "deregulated_nutrient_sensing" is appropriate. All key pathways cited are accurate and relevant.
Raw API responses
solver
{
"reasoning": "let-363 encodes the C. elegans ortholog of TOR (Target of Rapamycin), a central serine/threonine kinase that integrates nutrient, energy, and growth factor signals. In its normal active state, TOR (as part of TORC1) phosphorylates downstream effectors such as S6 kinase (rsks-1) and 4E-BP (ifg-1/ife-4), promoting anabolic processes including protein synthesis and suppressing autophagy. This active nutrient-sensing state is well-established to shorten lifespan in C. elegans; genetic reduction or RNAi knockdown of let-363 robustly extends lifespan. Thus, the normal kinase function of let-363 opposes longevity by driving growth and suppressing stress-response and autophagic pathways that promote survival.",
"confidence": 0.95,
"key_pathways": [
"TOR/TORC1 nutrient sensing pathway",
"S6 kinase (rsks-1) signaling",
"Autophagy suppression via mTORC1"
],
"mechanism_class": "deregulated_nutrient_sensing",
"longevity_influence": "anti_longevity"
}advisor
{
"notes": "The model correctly identified let-363 as anti_longevity with high confidence (0.95). The mechanistic reasoning is excellent: it correctly identifies let-363 as the C. elegans TOR ortholog, explains how active TOR promotes anabolic processes (via S6K/rsks-1 and 4E-BP phosphorylation), suppresses autophagy, and correctly states that RNAi knockdown of let-363 extends lifespan. The mechanism class of \"deregulated_nutrient_sensing\" is appropriate. All key pathways cited are accurate and relevant.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 5,
"ground_truth_questionable": false
}