Sirt7
M. musculus
sirtuin 7
What the model saw
Gene: Sirt7 Organism: Mus musculus Known functions: sirtuin 7. NAD-dependent protein deacetylase sirtuin-7. NAD+ binding. NAD-dependent protein lysine deacetylase activity. NAD-dependent protein-lysine depropionylase activity. chromatin binding. histone H3K18 deacetylase activity, NAD-dependent. protein binding. protein methyltransferase activity. protein-glutaryllysine deglutarylase activity. protein-succinyllysine desuccinylase activity.
View unredacted entry
sirtuin 7. NAD-dependent protein deacetylase sirtuin-7. NAD+ binding. NAD-dependent protein lysine deacetylase activity. NAD-dependent protein-lysine depropionylase activity. chromatin binding. histone H3K18 deacetylase activity, NAD-dependent. protein binding. protein methyltransferase activity. protein-glutaryllysine deglutarylase activity. protein-succinyllysine desuccinylase activity.
Solver output
SIRT7 is a nuclear NAD+-dependent deacylase with well-characterized histone H3K18 deacetylase activity, a mark associated with transcriptional repression of stress-response and oncogenic programs. By maintaining proper H3K18ac patterns through chromatin binding, SIRT7 preserves epigenetic homeostasis and suppresses aberrant gene expression that accumulates with age. Additionally, SIRT7 desuccinylates and deglutarylates mitochondrial and ribosomal proteins, supporting proteostasis and ribosome biogenesis fidelity. Sirt7 knockout mice display accelerated aging phenotypes including cardiac hypertrophy, inflammatory cardiomyopathy, and reduced lifespan, directly implicating its normal function in longevity promotion. Its dependence on NAD+ also links it to the broader NAD+/sirtuin axis of aging, where declining NAD+ levels with age reduce sirtuin activity and accelerate epigenetic drift.
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 Sirt7 in Mus musculus. The reasoning is excellent and mechanistically accurate: it correctly identifies SIRT7's role as a nuclear NAD+-dependent deacylase with H3K18 deacetylase activity, its role in chromatin homeostasis, and critically cites the key experimental evidence that Sirt7 knockout mice display accelerated aging phenotypes including cardiac hypertrophy and reduced lifespan. The mechanism class of epigenetic_alterations is appropriate. The model also correctly notes the broader NAD+/sirtuin axis connection and proteostasis roles. Confidence of 0.72 is reasonable given the specificity of the evidence.
Raw API responses
solver
{
"reasoning": "SIRT7 is a nuclear NAD+-dependent deacylase with well-characterized histone H3K18 deacetylase activity, a mark associated with transcriptional repression of stress-response and oncogenic programs. By maintaining proper H3K18ac patterns through chromatin binding, SIRT7 preserves epigenetic homeostasis and suppresses aberrant gene expression that accumulates with age. Additionally, SIRT7 desuccinylates and deglutarylates mitochondrial and ribosomal proteins, supporting proteostasis and ribosome biogenesis fidelity. Sirt7 knockout mice display accelerated aging phenotypes including cardiac hypertrophy, inflammatory cardiomyopathy, and reduced lifespan, directly implicating its normal function in longevity promotion. Its dependence on NAD+ also links it to the broader NAD+/sirtuin axis of aging, where declining NAD+ levels with age reduce sirtuin activity and accelerate epigenetic drift.",
"confidence": 0.72,
"key_pathways": [
"H3K18 deacetylation and chromatin homeostasis",
"NAD+/sirtuin longevity signaling",
"ribosome biogenesis and proteostasis via deacylation"
],
"mechanism_class": "epigenetic_alterations",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model correctly predicted pro_longevity for Sirt7 in Mus musculus. The reasoning is excellent and mechanistically accurate: it correctly identifies SIRT7's role as a nuclear NAD+-dependent deacylase with H3K18 deacetylase activity, its role in chromatin homeostasis, and critically cites the key experimental evidence that Sirt7 knockout mice display accelerated aging phenotypes including cardiac hypertrophy and reduced lifespan. The mechanism class of epigenetic_alterations is appropriate. The model also correctly notes the broader NAD+/sirtuin axis connection and proteostasis roles. Confidence of 0.72 is reasonable given the specificity of the evidence.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 5,
"ground_truth_questionable": false
}