Sirtuins: The Master Regulators of Longevity

Sirtuins 1-7: Functions and Activation Strategies

SIRT1 – Metabolic & Anti-Aging Master

• Regulates glucose metabolism, boosts mitochondria, reduces inflammation, and enhances DNA repair.

• Activation Strategies: Resveratrol, fasting, NMN/NR (NAD+ precursors), HIIT, and strength training.

SIRT2 – Cellular Defense Shield

• Prevents neurodegeneration, controls stress response, and maintains the cell cycle.

• Activation Strategies: Curcumin, ketogenic diet, fasting, DHA (omega-3s).

SIRT3 – The Mitochondrial Longevity Switch

• Enhances ATP production, reduces oxidative stress, and supports metabolic health.

• Activation Strategies: Cold exposure (cryotherapy, cold showers), NAD+ boosters, ketones.

SIRT4 – The Energy Gatekeeper

• Regulates insulin secretion, fatty acid oxidation, and amino acid metabolism.

• Activation Strategies: Intermittent fasting, L-carnitine, metformin/berberine.

SIRT5 – The Cellular Detoxifier

• Regulates ammonia detoxification, removes metabolic waste, and protects against oxidative stress.

• Activation Strategies: Glycine, NAC, sulforaphane (broccoli sprouts), alpha-ketoglutarate (AKG).

SIRT6 – The Genome Guardian

• Controls DNA repair, inflammation, skin health, and collagen synthesis.

• Activation Strategies: Fisetin, quercetin, Urolithin A (pomegranate extract), avoiding blue light at night.

SIRT7 – The Silent Longevity Guardian

• Supports protein synthesis, cardiovascular health, and DNA repair.

• Activation Strategies: Reishi and cordyceps mushrooms, EGCG (green tea extract), deep sleep optimization.

Best Practices to Activate Sirtuins for Longevity

• Intermittent fasting & ketosis – Triggers multiple sirtuins.

• HIIT & strength training – Increases SIRT1 and mitochondrial function.

• Cold exposure & sauna – Enhances metabolic efficiency.

• NAD+ precursors (NMN/NR) & resveratrol – Key for cellular repair.

• Polyphenols – Natural compounds that activate various sirtuins.

• Deep sleep & circadian rhythm optimization – Essential for SIRT7 activation.

Key Takeaways

• Sirtuins regulate aging, metabolism, and DNA repair, but decline with age.

• Each sirtuin requires specific activation strategies like fasting, exercise, NAD+ supplementation, and hormetic stress.

• Longevity is about systems thinking, not just one hack—combining diet, lifestyle, and supplements is key.

The question isn’t if you should be activating sirtuins—it’s how. Which one are you optimizing right now?