sir-2.1
C. elegans
NAD-dependent protein deacetylase sir-2.1
What the model saw
Gene: sir-2.1 Organism: Caenorhabditis elegans Known functions: NAD-dependent protein deacetylase sir-2.1. NAD+ binding. NAD-dependent protein lysine deacetylase activity. deacetylase activity. histone H3K14 deacetylase activity, NAD-dependent. histone H3K9 deacetylase activity, NAD-dependent. histone H4K deacetylase activity. histone H4K16 deacetylase activity, NAD-dependent. histone deacetylase activity. protein binding. transcription corepressor activity.
View unredacted entry
NAD-dependent protein deacetylase sir-2.1. NAD+ binding. NAD-dependent protein lysine deacetylase activity. deacetylase activity. histone H3K14 deacetylase activity, NAD-dependent. histone H3K9 deacetylase activity, NAD-dependent. histone H4K deacetylase activity. histone H4K16 deacetylase activity, NAD-dependent. histone deacetylase activity. protein binding. transcription corepressor activity.
Solver output
sir-2.1 is the C. elegans ortholog of yeast Sir2 and mammalian SIRT1, a founding member of the sirtuin family of NAD+-dependent protein deacetylases. Its NAD+-dependent deacetylase activity links cellular metabolic status (NAD+/NADH ratio) directly to chromatin remodeling via deacetylation of histone H3K9, H3K14, H4K16, and other lysine residues, promoting transcriptional silencing and genome stability. In C. elegans, sir-2.1 overexpression extends lifespan in a DAF-16/FOXO-dependent manner, as SIR-2.1 deacetylates and activates DAF-16, enhancing stress resistance and metabolic homeostasis. Its transcription corepressor activity further modulates gene expression programs associated with longevity, including suppression of pro-aging metabolic genes. The strict requirement for NAD+ as a cofactor positions sir-2.1 as a key sensor coupling nutrient/energy sensing to epigenetic regulation of aging.
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 sir-2.1 in C. elegans with high confidence (0.85). The mechanistic reasoning is accurate and detailed: sir-2.1 is indeed the C. elegans SIRT1 ortholog, its NAD+-dependent deacetylase activity links metabolic status to chromatin remodeling, and its lifespan extension via DAF-16/FOXO is well-established in the literature. The model correctly identifies the epigenetic mechanism, key pathways, and the nutrient-sensing role. The reasoning is thorough and scientifically sound.
Raw API responses
solver
{
"reasoning": "sir-2.1 is the C. elegans ortholog of yeast Sir2 and mammalian SIRT1, a founding member of the sirtuin family of NAD+-dependent protein deacetylases. Its NAD+-dependent deacetylase activity links cellular metabolic status (NAD+/NADH ratio) directly to chromatin remodeling via deacetylation of histone H3K9, H3K14, H4K16, and other lysine residues, promoting transcriptional silencing and genome stability. In C. elegans, sir-2.1 overexpression extends lifespan in a DAF-16/FOXO-dependent manner, as SIR-2.1 deacetylates and activates DAF-16, enhancing stress resistance and metabolic homeostasis. Its transcription corepressor activity further modulates gene expression programs associated with longevity, including suppression of pro-aging metabolic genes. The strict requirement for NAD+ as a cofactor positions sir-2.1 as a key sensor coupling nutrient/energy sensing to epigenetic regulation of aging.",
"confidence": 0.85,
"key_pathways": [
"NAD+/sirtuin-DAF-16/FOXO signaling",
"histone deacetylation and chromatin silencing",
"deregulated nutrient sensing via NAD+ metabolism"
],
"mechanism_class": "epigenetic_alterations",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model correctly predicted pro_longevity for sir-2.1 in C. elegans with high confidence (0.85). The mechanistic reasoning is accurate and detailed: sir-2.1 is indeed the C. elegans SIRT1 ortholog, its NAD+-dependent deacetylase activity links metabolic status to chromatin remodeling, and its lifespan extension via DAF-16/FOXO is well-established in the literature. The model correctly identifies the epigenetic mechanism, key pathways, and the nutrient-sensing role. The reasoning is thorough and scientifically sound.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 5,
"ground_truth_questionable": false
}