PeptideCompareSirtuin — Activators
Sirtuins are a family of seven NAD+-dependent proteins (SIRT1–SIRT7) involved in longevity, DNA repair, inflammation and metabolism. This topic covers the compounds studied as sirtuin activators.
The seven sirtuins
SIRT1 & SIRT2. SIRT1 is mainly nuclear and linked to regulation of gene expression, inflammation and circadian rhythm. SIRT2 is mainly found in the cytoplasm.
SIRT3, SIRT4 & SIRT5. Mitochondrial sirtuins. SIRT3 is studied for its role in oxidative stress defence and mitochondrial efficiency.
SIRT6 & SIRT7. Involved in DNA repair and metabolic regulation. Overexpression of SIRT6 extended lifespan in male mice in one study; this has not been shown in humans.
Compounds studied as sirtuin activators
Resveratrol. The best-known reported SIRT1 activator. Whether it activates SIRT1 directly has been disputed, and human evidence of benefit is limited. Pterostilbene is an analogue with higher bioavailability in animal studies.
Fisetin. A flavonoid studied both for senolytic activity and for sirtuin-related effects, mostly in cell and animal models. Human trials have been registered.
Apigenin. A flavone found in chamomile and parsley. It is reported to inhibit CD38, an enzyme that consumes NAD+. Data are preclinical.
NAD+. The essential cofactor of sirtuins: without it they cannot function, so NAD+ availability limits sirtuin activity.