unc-60
C. elegans
Actin-depolymerizing factor 2
What the model saw
Gene: unc-60 Organism: Caenorhabditis elegans Known functions: Actin-depolymerizing factor 2. actin filament binding.
View unredacted entry
Actin-depolymerizing factor 2. actin filament binding.
Solver output
UNC-60B is an ADF/cofilin-family actin-depolymerizing factor that binds actin filaments and promotes their turnover and dynamic remodeling. Proper actin cytoskeleton dynamics are essential for muscle function, intracellular trafficking, and autophagosome formation; loss of ADF/cofilin activity leads to actin filament stabilization and aggregation, impairing sarcomere organization in C. elegans body-wall muscle. Maintenance of actin dynamics supports proteostasis by enabling autophagic flux and preventing cytoskeletal protein aggregation, both of which are linked to healthspan and longevity. Additionally, actin remodeling is required for efficient mitochondrial fission/fusion dynamics and stem cell maintenance. Thus, the normal pro-depolymerizing function of UNC-60 is expected to support organismal health and longevity rather than oppose it.
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 unc-60. The mechanistic reasoning is sound and well-grounded: UNC-60B is indeed an ADF/cofilin-family protein involved in actin dynamics, and the model correctly identifies that maintaining proper actin cytoskeleton dynamics supports muscle function, proteostasis, and autophagic flux. The reasoning about loss of ADF/cofilin activity leading to actin aggregation and impaired sarcomere organization is accurate for C. elegans. The model appropriately connects these functions to longevity. Confidence of 0.62 is reasonable given the indirect nature of the connection. The mechanism class "other" is a bit vague but not incorrect. Overall a solid prediction with good mechanistic reasoning.
Raw API responses
solver
{
"reasoning": "UNC-60B is an ADF/cofilin-family actin-depolymerizing factor that binds actin filaments and promotes their turnover and dynamic remodeling. Proper actin cytoskeleton dynamics are essential for muscle function, intracellular trafficking, and autophagosome formation; loss of ADF/cofilin activity leads to actin filament stabilization and aggregation, impairing sarcomere organization in C. elegans body-wall muscle. Maintenance of actin dynamics supports proteostasis by enabling autophagic flux and preventing cytoskeletal protein aggregation, both of which are linked to healthspan and longevity. Additionally, actin remodeling is required for efficient mitochondrial fission/fusion dynamics and stem cell maintenance. Thus, the normal pro-depolymerizing function of UNC-60 is expected to support organismal health and longevity rather than oppose it.",
"confidence": 0.62,
"key_pathways": [
"actin cytoskeleton dynamics / ADF-cofilin pathway",
"autophagy and proteostasis",
"muscle sarcomere maintenance"
],
"mechanism_class": "other",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model correctly predicted pro_longevity for unc-60. The mechanistic reasoning is sound and well-grounded: UNC-60B is indeed an ADF/cofilin-family protein involved in actin dynamics, and the model correctly identifies that maintaining proper actin cytoskeleton dynamics supports muscle function, proteostasis, and autophagic flux. The reasoning about loss of ADF/cofilin activity leading to actin aggregation and impaired sarcomere organization is accurate for C. elegans. The model appropriately connects these functions to longevity. Confidence of 0.62 is reasonable given the indirect nature of the connection. The mechanism class \"other\" is a bit vague but not incorrect. Overall a solid prediction with good mechanistic reasoning.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 4,
"ground_truth_questionable": false
}