Gene
SIRT6
Last updated Sat May 30 2026 00:00:00 GMT+0000 (Coordinated Universal Time)
Why SIRT6 stands out
Among the seven mammalian sirtuins, SIRT6 has the clearest single-protein impact on lifespan in mice:
- Knockout mice show extreme progeria phenotypes (hypoglycaemia, organ failure, ~4-week lifespan).
- Overexpression in males extends lifespan by ~15%.
- Adenoviral SIRT6 delivery to old mice extends remaining lifespan.
Mechanisms
- Maintains telomere integrity through H3K9 deacetylation at telomeric chromatin.
- Represses LINE-1 retrotransposons, which de-repress with age and contribute to inflammaging.
- Promotes DNA double-strand break repair.
- Regulates glucose homeostasis.
Therapeutic interest
- Small-molecule SIRT6 activators are in pre-clinical development.
- Gene-therapy approaches (AAV-SIRT6) are being explored.
- Naked mole-rats have especially robust SIRT6 activity — another reason for comparative-biology focus on this gene (Gorbunova & Seluanov).
Practical takeaway
No clinical genotyping for SIRT6 variants is recommended. Lifestyle interventions that raise NAD+ support all sirtuins.
Related entries
Sirtuins, NAD+ precursors, Telomere attrition, Vera Gorbunova & Andrei Seluanov.
References
- Roichman, A. et al. Restoration of energy homeostasis by SIRT6 extends healthy lifespan. Nat. Commun. 12, 3208 (2021).