S6k
D. melanogaster
Ribosomal protein S6 kinase
What the model saw
Gene: S6k Organism: Drosophila melanogaster Known functions: Ribosomal protein S6 kinase. ribosomal protein S6 kinase. ATP binding. nucleotide binding. protein binding. protein kinase activity. protein serine/threonine kinase activity. ribosomal protein S6 kinase activity.
View unredacted entry
Ribosomal protein S6 kinase. ribosomal protein S6 kinase. ATP binding. nucleotide binding. protein binding. protein kinase activity. protein serine/threonine kinase activity. ribosomal protein S6 kinase activity.
Solver output
S6K (ribosomal protein S6 kinase) is the canonical downstream effector of the TOR (Target of Rapamycin) signaling pathway, a central nutrient-sensing hub. Its primary molecular function — phosphorylating ribosomal protein S6 and other translational regulators — promotes anabolic processes including protein synthesis and cell growth. Hyperactivation of TOR-S6K signaling is a well-established driver of accelerated aging; conversely, genetic or pharmacological reduction of S6K activity (e.g., via rapamycin or loss-of-function mutations) consistently extends lifespan across multiple model organisms including Drosophila. In flies, reduced dS6K activity extends lifespan by attenuating mTORC1-driven anabolism and promoting stress resistance. S6K also phosphorylates and inhibits IRS-1 (insulin receptor substrate), creating a negative feedback loop that suppresses insulin/IGF-1 signaling, but the net effect of S6K activity on aging is pro-aging due to its promotion of mTOR-driven growth and suppression of autophagy. Thus, the normal (active) function of S6K 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 S6k as anti_longevity with high confidence (0.93). The mechanistic reasoning is excellent and accurate: S6K is the canonical downstream effector of TOR/mTORC1 signaling, promotes anabolic processes, and its reduction extends lifespan in Drosophila. The model correctly identifies the key pathways (TOR signaling, insulin/IGF-1 signaling, translational regulation) and accurately notes the IRS-1 negative feedback loop. The reasoning that active S6K opposes longevity (hence anti_longevity classification) is well-supported by the literature.
Raw API responses
solver
{
"reasoning": "S6K (ribosomal protein S6 kinase) is the canonical downstream effector of the TOR (Target of Rapamycin) signaling pathway, a central nutrient-sensing hub. Its primary molecular function — phosphorylating ribosomal protein S6 and other translational regulators — promotes anabolic processes including protein synthesis and cell growth. Hyperactivation of TOR-S6K signaling is a well-established driver of accelerated aging; conversely, genetic or pharmacological reduction of S6K activity (e.g., via rapamycin or loss-of-function mutations) consistently extends lifespan across multiple model organisms including Drosophila. In flies, reduced dS6K activity extends lifespan by attenuating mTORC1-driven anabolism and promoting stress resistance. S6K also phosphorylates and inhibits IRS-1 (insulin receptor substrate), creating a negative feedback loop that suppresses insulin/IGF-1 signaling, but the net effect of S6K activity on aging is pro-aging due to its promotion of mTOR-driven growth and suppression of autophagy. Thus, the normal (active) function of S6K opposes longevity.",
"confidence": 0.93,
"key_pathways": [
"TOR (mTORC1) signaling",
"Insulin/IGF-1 signaling pathway",
"Translational regulation and ribosome biogenesis"
],
"mechanism_class": "deregulated_nutrient_sensing",
"longevity_influence": "anti_longevity"
}advisor
{
"notes": "The model correctly predicted S6k as anti_longevity with high confidence (0.93). The mechanistic reasoning is excellent and accurate: S6K is the canonical downstream effector of TOR/mTORC1 signaling, promotes anabolic processes, and its reduction extends lifespan in Drosophila. The model correctly identifies the key pathways (TOR signaling, insulin/IGF-1 signaling, translational regulation) and accurately notes the IRS-1 negative feedback loop. The reasoning that active S6K opposes longevity (hence anti_longevity classification) is well-supported by the literature.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 5,
"ground_truth_questionable": false
}