SIRT1 is an enzyme located primarily in the cell nucleus that deacetylates transcription factors that contribute to cellular regulation (reaction to stressors, longevity).

[10] Furthermore, SIRT1 was shown to de-acetylate and affect the activity of both members of the PGC1-alpha/ERR-alpha complex, which are essential metabolic regulatory transcription factors.

[33][34] In the roundworm, Caenorhabditis elegans, Sir-2.1 is used to denote the gene product most similar to yeast Sir2 in structure and activity.

[35][36] Sirtuins act primarily by removing acetyl groups from lysine residues within proteins in the presence of NAD+; thus, they are classified as "NAD+-dependent deacetylases" and have EC number 3.5.1.

The HDAC activity of Sir2 results in tighter packaging of chromatin and a reduction in transcription at the targeted gene locus.

[38] In particular, the silencing activity of Sir2, in complex with Sir3 and Sir4, at the HM loci prevents simultaneous expression of both mating factors which can cause sterility and shortened lifespan.

[40] However, mice lacking the SIRT1 gene (the sir2 biological equivalent) were smaller than normal at birth, often died early or became sterile.

NF-κB increases the levels of the microRNA miR-34a (which inhibits nicotinamide adenine dinucleotide NAD+ synthesis) by binding to its promoter region.

[52] WRN protein is a RecQ helicase, and in its mutated form gives rise to Werner syndrome, a genetic condition in humans characterized by numerous features of premature aging.

These findings link SIRT1 function to HR, a DNA repair process that is likely necessary for maintaining the integrity of the genome during aging.