Mice lacking the SIRT1 gene (the sir2 biological equivalent) were smaller than normal at birth, often died early or became sterile.
- Lamin A is a protein that had been identified as a direct activator of Sirtuin 1 during a study on Progeria.
- Resveratrol has been claimed to be an activator of Sirtuin 1, but this effect has been disputed based on the fact that the initially used activity assay, using a non-physiological substrate peptide, can produce artificial results.Resveratrol increases the expression of SIRT1, meaning that it does increase the activity of SIRT1, though not necessarily by direct activation. However, resveratrol was later shown to directly activate Sirtuin 1 against non-modified peptide substrates. Resveratrol also enhances the binding between Sirtuin 1 and Lamin A.
- SRT-1720 was also claimed to be an activator, but this now has been questioned
- Sir2 (whose homolog in mammals is known as SIRT1) was the first gene of the sirtuin genes to be found. It was found in budding yeast, and, since then, members of this highly conserved family have been found in nearly all organisms studied.Sirtuins are hypothesized to play a key role in an organism’s response to stresses (such as heat or starvation) and to be responsible for the lifespan-extending effects of calorie restriction.
In the roundworm, Caenorhabditis elegans, Sir-2.1 is used to denote the gene product most similar to yeast Sir2 in structure and activity.