[2][3] They are ancient in animal evolution and appear to possess a highly conserved structure throughout all kingdoms of life.

From in vitro studies, sirtuins were thought to be implicated in influencing cellular processes like aging, transcription, apoptosis, inflammation[8] and stress resistance, as well as energy efficiency and alertness during low-calorie situations.

[9] As of 2018, there was no clinical evidence that sirtuins affect human aging,[10] and a 2022 review criticized researchers who propagate this claim.

[12] This hydrolysis yields O-acetyl-ADP-ribose, the deacetylated substrate and nicotinamide, which is an inhibitor of sirtuin activity itself.

[16] Mammals possess seven sirtuins (SIRT1–7) that occupy different subcellular compartments: SIRT1, SIRT6 and SIRT7 are predominantly in the nucleus, SIRT2 in the cytoplasm, and SIRT3, SIRT4 and SIRT5 in the mitochondria.

[17][18] Interest in the metabolism of NAD+ heightened after the year 2000 discovery by Shin-ichiro Imai and coworkers in the Guarente laboratory that sirtuins are NAD+-dependent protein deacetylases .

These genes are designated as belonging to different classes (I-IV), depending on their amino acid sequence structure.

[29] SIRT6 is a chromatin-associated protein and in mammalian cells is required for base excision repair of DNA damage.