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Sirtuin — Activators

Sirtuins are a family of 7 proteins (SIRT1–SIRT7) that regulate longevity, DNA repair, inflammation, and metabolism. They require NAD+ to function — and they can be activated by specific compounds.

SIRT1 & SIRT2
Nuclear sirtuins. SIRT1 regulates gene expression, inflammation and circadian rhythm. Activated by resveratrol, NAD+, and caloric restriction.
SIRT3, SIRT4 & SIRT5
Mitochondrial sirtuins. SIRT3 protects against oxidative stress and improves mitochondrial efficiency. Key target for longevity interventions.
SIRT6 & SIRT7
DNA repair and metabolic regulation. SIRT6 overexpression extends lifespan in mice. One of the most exciting longevity targets in current research.
KEY SIRTUIN ACTIVATORS
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Resveratrol — the original sirtuin activator
Activates SIRT1 directly. Works synergistically with NAD+. Famously part of David Sinclair's protocol at 1g/day. Must be taken with fat for absorption. Pterostilbene is the more bioavailable, longer-lasting analogue.
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Fisetin — senolytic and sirtuin activator
A flavonoid with dual action: SIRT1 activation and senolytic activity. One of the most potent compounds in the longevity stack. Human trials ongoing at Mayo Clinic.
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Apigenin — SIRT1 activator & CD38 inhibitor
Inhibits CD38 (which breaks down NAD+) while activating SIRT1. Found in chamomile and parsley. At 50–100mg/day it preserves NAD+ and amplifies sirtuin activity.
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NMN / NAD+ — the fuel sirtuins run on
Without NAD+, sirtuins cannot function regardless of how many activators you take. NAD+ is the essential cofactor — activators without adequate NAD+ levels have limited effect.
Read: NAD+ synergists — what stacks with NMN and why
Covers resveratrol, apigenin, quercetin and more in detail
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