sesn-1
C. elegans
Sestrin homolog
What the model saw
Gene: sesn-1 Organism: Caenorhabditis elegans Known functions: Sestrin homolog. L-leucine binding. oxidoreductase activity, acting on peroxide as acceptor.
View unredacted entry
Sestrin homolog. L-leucine binding. oxidoreductase activity, acting on peroxide as acceptor.
Solver output
Sestrin homologs are well-characterized dual-function proteins that act as both antioxidants (via peroxiredoxin-regenerating oxidoreductase activity) and as leucine sensors that inhibit TORC1 signaling. The L-leucine binding function of sesn-1 places it directly in the GATOR2/TORC1 nutrient-sensing axis: upon leucine deprivation, Sestrin binds and inhibits GATOR2, thereby suppressing mTORC1 activity and promoting autophagy and stress resistance — a well-established pro-longevity pathway. Additionally, its oxidoreductase/peroxidase activity reduces oxidative damage by regenerating peroxiredoxins, mitigating ROS-induced macromolecular damage. Together, these two activities — TORC1 inhibition under amino acid limitation and ROS detoxification — are canonical pro-longevity mechanisms conserved from worms to mammals. Loss of sestrin function in model organisms typically shortens lifespan and reduces stress resistance, confirming its pro-longevity role.
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 pro_longevity for sesn-1 in C. elegans with high confidence (0.82). The mechanistic reasoning is excellent and well-grounded: it correctly identifies the dual role of Sestrin as (1) a leucine sensor that inhibits GATOR2/TORC1 signaling to promote autophagy and stress resistance, and (2) an oxidoreductase/peroxidase that regenerates peroxiredoxins to reduce oxidative damage. Both mechanisms are well-established pro-longevity pathways. The model also correctly notes that loss of sestrin function shortens lifespan, consistent with its pro-longevity classification. The reasoning is detailed, accurate, and mechanistically sound.
Raw API responses
solver
{
"reasoning": "Sestrin homologs are well-characterized dual-function proteins that act as both antioxidants (via peroxiredoxin-regenerating oxidoreductase activity) and as leucine sensors that inhibit TORC1 signaling. The L-leucine binding function of sesn-1 places it directly in the GATOR2/TORC1 nutrient-sensing axis: upon leucine deprivation, Sestrin binds and inhibits GATOR2, thereby suppressing mTORC1 activity and promoting autophagy and stress resistance — a well-established pro-longevity pathway. Additionally, its oxidoreductase/peroxidase activity reduces oxidative damage by regenerating peroxiredoxins, mitigating ROS-induced macromolecular damage. Together, these two activities — TORC1 inhibition under amino acid limitation and ROS detoxification — are canonical pro-longevity mechanisms conserved from worms to mammals. Loss of sestrin function in model organisms typically shortens lifespan and reduces stress resistance, confirming its pro-longevity role.",
"confidence": 0.82,
"key_pathways": [
"TORC1/mTOR nutrient sensing (GATOR2 inhibition via leucine binding)",
"Peroxiredoxin regeneration / ROS detoxification",
"Autophagy induction downstream of TORC1 inhibition"
],
"mechanism_class": "deregulated_nutrient_sensing",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model correctly predicted pro_longevity for sesn-1 in C. elegans with high confidence (0.82). The mechanistic reasoning is excellent and well-grounded: it correctly identifies the dual role of Sestrin as (1) a leucine sensor that inhibits GATOR2/TORC1 signaling to promote autophagy and stress resistance, and (2) an oxidoreductase/peroxidase that regenerates peroxiredoxins to reduce oxidative damage. Both mechanisms are well-established pro-longevity pathways. The model also correctly notes that loss of sestrin function shortens lifespan, consistent with its pro-longevity classification. The reasoning is detailed, accurate, and mechanistically sound.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 5,
"ground_truth_questionable": false
}