Sirtuin Activation

Sirtuins are NAD+-dependent deacetylases that link cellular energy status to gene expression, DNA repair and mitochondrial biogenesis. Their activity depends on NAD+ availability, which declines with age. The field's credibility problem stems from the original resveratrol activation assays, which used a fluorophore-tagged substrate that produced activation not seen with native substrates. Human trials of resveratrol and NAD+ precursors reliably raise blood NAD+ but have not yet demonstrated meaningful clinical outcomes. Treat sirtuin activation as a promising mechanism, not a proven intervention.

1) Exercise regularly — the most reliable physiological sirtuin and NAD+ activator, particularly aerobic and interval training. 2) Practise time-restricted eating or intermittent caloric restriction, the intervention with the strongest mechanistic and animal evidence. 3) Avoid chronic caloric surplus, which suppresses sirtuin activity through high NADH ratios. 4) Get adequate sleep, since circadian disruption directly impairs NAD+ cycling. 5) Eat niacin-containing foods to supply NAD+ precursors from the diet. 6) Limit alcohol, which consumes NAD+ during metabolism. 7) Treat NAD+ precursor supplements as experimental: they raise blood NAD+ but have not yet shown clinical benefit in humans. 8) Be sceptical of anti-ageing marketing built on the discredited resveratrol activation assays.

• •Regular aerobic and interval exercise
• •Time-restricted eating
• •Avoiding chronic caloric surplus
• •Sleep and circadian regularity
• •Alcohol moderation
• •Dietary niacin sources