Sirtuins (SIRT1-7) are the longevity proteins at the centre of anti-aging research. Complete guide to what they are, how they work and how to activate them.
⚡ Quick AnswerLast Reviewed: July 2026
Sirtuins (SIRT1-7) are a family of NAD+-dependent proteins involved in cellular longevity, metabolic regulation, DNA repair and stress resistance. They are activated by trans-resveratrol and require NAD+ (provided by NMN supplementation) to function. Declining NAD+ with age reduces sirtuin activity.
What Are Sirtuins?
Sirtuins are a family of seven proteins (SIRT1-7) that were identified as key regulators of lifespan in model organisms and have since been extensively studied in human cells. They are classified as protein deacylases — they remove acyl groups (typically acetyl groups) from lysine residues on target proteins, regulating their activity.
What Each Sirtuin Does
SIRT1: The most studied — regulates gene expression, metabolism, inflammation and circadian rhythm
SIRT3: Mitochondrial — regulates mitochondrial function and oxidative stress responses
SIRT5: Mitochondrial — regulates ammonia metabolism and fatty acid oxidation
SIRT6: Nuclear — DNA repair, telomere maintenance, inflammation regulation
SIRT7: Nuclear — ribosomal DNA transcription regulation
How to Activate Sirtuins
Sirtuins require NAD+ as a co-substrate to function — without adequate NAD+, sirtuin activity is impaired regardless of other activation signals. The two primary supplement interventions are: NMN (raises NAD+ levels) and trans-resveratrol (directly activates SIRT1 by lowering its activation threshold).
Sirtuins (SIRT1-7) are NAD+-dependent proteins that regulate cellular longevity, metabolic function, DNA repair and stress resistance.
Two approaches: raise NAD+ levels (via NMN supplementation) and directly activate SIRT1 (via trans-resveratrol). Caloric restriction and exercise also activate sirtuins.
NAD+ is a co-substrate for sirtuin deacylase activity — sirtuins consume NAD+ to perform their regulatory functions. Without adequate NAD+, sirtuins cannot function at optimal levels.
Sirtuin activity declines with age as NAD+ declines. Restoring sirtuin function via NAD+ supplementation is a primary target of longevity research.
Trans-resveratrol activates SIRT1 in cell and animal models. NMN raises NAD+ in published human trials. The downstream longevity effects in humans are still being characterised.
Disclaimer: For informational purposes only. Dietary supplements — not medicines. Not intended to diagnose, treat, cure or prevent any disease. FDA/MHRA not evaluated. Individual results vary. Consult healthcare professional. Affiliate commissions may be earned. Full disclaimer →