tufm-1
C. elegans
Elongation factor Tu, mitochondrial
What the model saw
Gene: tufm-1 Organism: Caenorhabditis elegans Known functions: Elongation factor Tu, mitochondrial. GTP binding. GTPase activity. translation elongation factor activity.
View unredacted entry
Elongation factor Tu, mitochondrial. GTP binding. GTPase activity. translation elongation factor activity.
Solver output
TUFM-1 encodes the mitochondrial elongation factor Tu (EF-Tu), a GTPase that delivers aminoacyl-tRNAs to the mitochondrial ribosome during translation elongation. Proper mitochondrial translation is essential for synthesizing the 13 core subunits of the oxidative phosphorylation complexes encoded by the mitochondrial genome. Paradoxically, in C. elegans, partial reduction of mitochondrial translation (including via RNAi of EF-Tu homologs) activates the mitochondrial unfolded protein response (UPRmt) and has been shown to extend lifespan through retrograde signaling involving ATFS-1. This hormetic mitochondrial stress response improves mitochondrial quality control and stress resilience. However, the normal (wild-type) function of tufm-1 supports efficient mitochondrial protein synthesis, which maintains respiratory chain integrity and reduces ROS-mediated damage — both pro-longevity effects. The balance of evidence in C. elegans suggests that the gene's normal function, by sustaining mitochondrial homeostasis, is net pro-longevity, though partial loss-of-function can also extend life via UPRmt.
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 actually acknowledges the key paradox — that partial loss of mitochondrial translation (including EF-Tu homologs) can extend lifespan via UPRmt — but then incorrectly concludes that the gene's normal function is "net pro-longevity." In C. elegans, tufm-1 is classified as anti_longevity, meaning its normal function suppresses longevity (i.e., reducing its activity extends lifespan). The model correctly identified the UPRmt mechanism but drew the wrong conclusion about which direction the gene influences longevity. The model essentially had the right mechanistic picture but assigned the wrong label, likely because it conflated "supports mitochondrial homeostasis" with "pro-longevity" rather than recognizing that in C. elegans, mitochondrial translation reduction is a well-established lifespan-extending intervention. Confidence was 0.62, which is moderate but still wrong.
Raw API responses
solver
{
"reasoning": "TUFM-1 encodes the mitochondrial elongation factor Tu (EF-Tu), a GTPase that delivers aminoacyl-tRNAs to the mitochondrial ribosome during translation elongation. Proper mitochondrial translation is essential for synthesizing the 13 core subunits of the oxidative phosphorylation complexes encoded by the mitochondrial genome. Paradoxically, in C. elegans, partial reduction of mitochondrial translation (including via RNAi of EF-Tu homologs) activates the mitochondrial unfolded protein response (UPRmt) and has been shown to extend lifespan through retrograde signaling involving ATFS-1. This hormetic mitochondrial stress response improves mitochondrial quality control and stress resilience. However, the normal (wild-type) function of tufm-1 supports efficient mitochondrial protein synthesis, which maintains respiratory chain integrity and reduces ROS-mediated damage — both pro-longevity effects. The balance of evidence in C. elegans suggests that the gene's normal function, by sustaining mitochondrial homeostasis, is net pro-longevity, though partial loss-of-function can also extend life via UPRmt.",
"confidence": 0.62,
"key_pathways": [
"mitochondrial translation elongation",
"oxidative phosphorylation complex assembly",
"mitochondrial unfolded protein response (UPRmt)"
],
"mechanism_class": "mitochondrial_dysfunction",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model predicted pro_longevity but the ground truth is anti_longevity. The model's reasoning actually acknowledges the key paradox — that partial loss of mitochondrial translation (including EF-Tu homologs) can extend lifespan via UPRmt — but then incorrectly concludes that the gene's normal function is \"net pro-longevity.\" In C. elegans, tufm-1 is classified as anti_longevity, meaning its normal function suppresses longevity (i.e., reducing its activity extends lifespan). The model correctly identified the UPRmt mechanism but drew the wrong conclusion about which direction the gene influences longevity. The model essentially had the right mechanistic picture but assigned the wrong label, likely because it conflated \"supports mitochondrial homeostasis\" with \"pro-longevity\" rather than recognizing that in C. elegans, mitochondrial translation reduction is a well-established lifespan-extending intervention. Confidence was 0.62, which is moderate but still wrong.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 2,
"ground_truth_questionable": false
}