Sirt2
D. melanogaster
Sirtuin 2
What the model saw
Gene: Sirt2 Organism: Drosophila melanogaster Known functions: Sirtuin 2. sirtuin 2. NAD binding. NAD+ binding. NAD-dependent protein lysine deacetylase activity. catalytic activity. histone deacetylase activity. histone deacetylase activity, NAD-dependent. protein lysine deacetylase activity.
View unredacted entry
Sirtuin 2. sirtuin 2. NAD binding. NAD+ binding. NAD-dependent protein lysine deacetylase activity. catalytic activity. histone deacetylase activity. histone deacetylase activity, NAD-dependent. protein lysine deacetylase activity.
Solver output
Sirt2 is a NAD+-dependent protein lysine deacetylase (sirtuin family) that removes acetyl groups from histone and non-histone substrates, directly linking cellular energy/redox status (NAD+/NADH ratio) to chromatin regulation and protein function. Sirtuins are broadly conserved longevity factors; in Drosophila, NAD+-dependent deacetylase activity modulates histone acetylation landscapes, helping maintain epigenetic fidelity that declines with age. By coupling NAD+ availability to deacetylation of histones and key metabolic/stress-response proteins, Sirt2 activity supports genomic and epigenetic stability, suppresses age-associated hyperacetylation, and promotes stress resistance. The NAD-dependence also ties Sirt2 function to nutrient-sensing pathways (e.g., AMPK/mTOR axis), further reinforcing its pro-longevity role. Loss of sirtuin deacetylase activity in model organisms is generally associated with shortened lifespan and accelerated aging phenotypes.
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 Drosophila Sirt2. The mechanistic reasoning is sound - sirtuins are well-established longevity factors, and the NAD+-dependent deacetylase activity linking energy sensing to epigenetic regulation is a legitimate mechanism. The reasoning is somewhat generic (applies to sirtuins broadly rather than Sirt2 specifically in Drosophila), but it's not wrong. The model appropriately notes the sirtuin family's conserved role in longevity and correctly identifies epigenetic alterations as the primary mechanism class. Confidence of 0.78 is reasonable given the general knowledge about sirtuins.
Raw API responses
solver
{
"reasoning": "Sirt2 is a NAD+-dependent protein lysine deacetylase (sirtuin family) that removes acetyl groups from histone and non-histone substrates, directly linking cellular energy/redox status (NAD+/NADH ratio) to chromatin regulation and protein function. Sirtuins are broadly conserved longevity factors; in Drosophila, NAD+-dependent deacetylase activity modulates histone acetylation landscapes, helping maintain epigenetic fidelity that declines with age. By coupling NAD+ availability to deacetylation of histones and key metabolic/stress-response proteins, Sirt2 activity supports genomic and epigenetic stability, suppresses age-associated hyperacetylation, and promotes stress resistance. The NAD-dependence also ties Sirt2 function to nutrient-sensing pathways (e.g., AMPK/mTOR axis), further reinforcing its pro-longevity role. Loss of sirtuin deacetylase activity in model organisms is generally associated with shortened lifespan and accelerated aging phenotypes.",
"confidence": 0.78,
"key_pathways": [
"NAD+-dependent deacetylation / sirtuin signaling",
"Histone acetylation and epigenetic regulation",
"Nutrient sensing and metabolic homeostasis"
],
"mechanism_class": "epigenetic_alterations",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model correctly predicted pro_longevity for Drosophila Sirt2. The mechanistic reasoning is sound - sirtuins are well-established longevity factors, and the NAD+-dependent deacetylase activity linking energy sensing to epigenetic regulation is a legitimate mechanism. The reasoning is somewhat generic (applies to sirtuins broadly rather than Sirt2 specifically in Drosophila), but it's not wrong. The model appropriately notes the sirtuin family's conserved role in longevity and correctly identifies epigenetic alterations as the primary mechanism class. Confidence of 0.78 is reasonable given the general knowledge about sirtuins.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 4,
"ground_truth_questionable": false
}