How sirtuins use NAD+ to edit protein activity
Sirtuins are a family of seven enzymes in mammals (SIRT1 through SIRT7) that remove acetyl groups, and in some cases other acyl groups, from lysine residues on histones and other proteins. What sets them apart from classical deacetylases is their dependence on NAD+ as a co-substrate: for each deacetylation they consume one NAD+ molecule and release nicotinamide. This ties their activity directly to the cell's metabolic and energy state.
By deacetylating histones, sirtuins can tighten chromatin and silence genes; by acting on transcription factors and metabolic enzymes, they reprogram pathways governing fuel use, stress responses, and DNA repair.
Where the family acts and what is still uncertain
The seven sirtuins differ in location and role: SIRT1, SIRT6, and SIRT7 work largely in the nucleus, SIRT3, SIRT4, and SIRT5 in mitochondria, and SIRT2 mainly in the cytoplasm. Their NAD+ dependence is why declining NAD+ with age is thought to blunt sirtuin function.
Claims that activating sirtuins (for example with resveratrol or NAD+ precursors) slows human aging remain preliminary and debated. This is general educational information on cell biology, not medical or supplement advice; consult a qualified professional.