Sirtuins (SIRT1–SIRT7)

What they are

Sirtuins are seven (SIRT1–7) NAD⁺-dependent deacylase enzymes descended from the yeast Sir2 gene. They sit in different cellular compartments and act on different substrates:

• SIRT1, SIRT6, SIRT7 — nucleus, chromatin.
• SIRT3, SIRT4, SIRT5 — mitochondria.
• SIRT2 — cytoplasm.

Why they matter

Sirtuin overexpression extends lifespan in worms, flies, and mice (in sex- and isoform-specific ways). They couple nutrient state (NAD⁺ availability) to chromatin remodelling, DNA repair, mitochondrial function, and metabolic flexibility.

SIRT6 stands out

SIRT6 knock-out mice show progeroid phenotype; SIRT6 transgenic males live longer. SIRT6 maintains telomere integrity and represses LINE-1 retrotransposons that accumulate with age.

Activators

• NAD⁺ raising compounds: NR/NMN.
• Sirtuin-activating compounds (STACs): resveratrol, pterostilbene (controversial mechanistic literature).
• Caloric restriction and exercise (indirect via NAD⁺).

Related entries

NAD+ precursors, Epigenetic alterations, mTOR, AMPK.