cct-6
C. elegans
T-complex protein 1 subunit zeta
What the model saw
Gene: cct-6 Organism: Caenorhabditis elegans Known functions: T-complex protein 1 subunit zeta. ATP binding. ATP hydrolysis activity. ATP-dependent protein folding chaperone. unfolded protein binding.
View unredacted entry
T-complex protein 1 subunit zeta. ATP binding. ATP hydrolysis activity. ATP-dependent protein folding chaperone. unfolded protein binding.
Solver output
cct-6 encodes the zeta subunit of the TRiC/CCT chaperonin complex, which uses ATP hydrolysis to fold newly synthesized and stress-denatured proteins. Maintenance of proteostasis is a central hallmark of longevity; the TRiC complex is essential for folding cytoskeletal proteins (e.g., actin, tubulin) and preventing toxic protein aggregation. In C. elegans, robust chaperone activity suppresses the accumulation of misfolded and aggregated proteins that drive age-related proteotoxicity. Loss of TRiC subunits accelerates protein aggregation and shortens lifespan, while enhanced chaperone capacity is associated with longevity. The ATP-dependent unfolded protein binding activity of CCT-6 directly supports proteome integrity across the organism's lifespan.
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 predicted pro_longevity but the ground truth is anti_longevity. The model's reasoning is plausible on the surface — TRiC/CCT chaperonins do fold proteins and maintain proteostasis — but it incorrectly assumed that a chaperone gene must be pro-longevity. In C. elegans, cct-6 (and other TRiC subunits) have been shown to have anti-longevity effects, likely because the TRiC complex assists in folding proteins that promote growth and reproduction at the expense of longevity (e.g., via IIS pathway components or other pro-aging factors). The model failed to consider that chaperones can also fold pro-aging proteins, and that RNAi knockdown of TRiC subunits can actually extend lifespan in C. elegans. The model was moderately confident (0.72) in the wrong direction. The mechanistic reasoning, while internally consistent, led to the wrong conclusion.
Raw API responses
solver
{
"reasoning": "cct-6 encodes the zeta subunit of the TRiC/CCT chaperonin complex, which uses ATP hydrolysis to fold newly synthesized and stress-denatured proteins. Maintenance of proteostasis is a central hallmark of longevity; the TRiC complex is essential for folding cytoskeletal proteins (e.g., actin, tubulin) and preventing toxic protein aggregation. In C. elegans, robust chaperone activity suppresses the accumulation of misfolded and aggregated proteins that drive age-related proteotoxicity. Loss of TRiC subunits accelerates protein aggregation and shortens lifespan, while enhanced chaperone capacity is associated with longevity. The ATP-dependent unfolded protein binding activity of CCT-6 directly supports proteome integrity across the organism's lifespan.",
"confidence": 0.72,
"key_pathways": [
"TRiC/CCT chaperonin-mediated protein folding",
"proteostasis network",
"ATP-dependent chaperone activity"
],
"mechanism_class": "loss_of_proteostasis",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model predicted pro_longevity but the ground truth is anti_longevity. The model's reasoning is plausible on the surface — TRiC/CCT chaperonins do fold proteins and maintain proteostasis — but it incorrectly assumed that a chaperone gene must be pro-longevity. In C. elegans, cct-6 (and other TRiC subunits) have been shown to have anti-longevity effects, likely because the TRiC complex assists in folding proteins that promote growth and reproduction at the expense of longevity (e.g., via IIS pathway components or other pro-aging factors). The model failed to consider that chaperones can also fold pro-aging proteins, and that RNAi knockdown of TRiC subunits can actually extend lifespan in C. elegans. The model was moderately confident (0.72) in the wrong direction. The mechanistic reasoning, while internally consistent, led to the wrong conclusion.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 3,
"ground_truth_questionable": false
}