Sirtuine

Sirtuins, also known as Sir2 like proteins, form a family of multifunctional enzymes from the group of histone deacetylases (HDAC class III). Sirtuins are evolutionarily highly conserved and occur in all living organisms from viruses to mammals (including humans). Sirtuins deacetylate the histone proteins via a NAD+-dependent mechanism. These post-translational changes in the side chains of individual amino acids of histone proteins regulate the activation and silencing of certain gene segments (such control mechanisms of gene expression beyond the DNA sequence, which itself is not altered, are called epigenetics). Sirtuins can also interact with non-histone proteins such as the tumour suppressor protein p53.

In humans 7 different sirtuins are distinguished (Sirituin1- Sirtuin7).

Because of their ability to modify numerous enzymes and proteins that play a key role in various diseases, the role of sirtuins in carcinogenesis and cell ageing, Alzheimer's disease, Parkinson's disease, diabetes mellitus and obesity is being studied intensively.

The observation that activation of the SIR2 gene can prolong the lifespan of Saccharomyces cerevisiae cultures, as well as of Caenorhabditis elegans and Drosophila melanogaster (the so-called Methuselah gene), inspired the fantasies of researchers into ageing for a long time. These earlier research results could not be reproduced later (Burnett C et al. 2011).

In yeast cultures, however, it was shown that a niacin deficiency leads to an upregulation of sirtuin 2 and sirtuin 4 and to increased DNA damage. This effect was reversible by niacinamide (ZhaoY 2016). Sirtuin activation further increases the sensitivity to UV damage. Nicotinamide and also resveratol inhibit sirtuin 1 activation (Bayerl C 2017).

The name Sirtuin is derived from the gene Sir2 (silent mating type information regulation 2).

1. Bayerl C (2017) Vitamin B3 in cosmetic dermatology. Act dermatol 43: 431-433.
2. Burnett C et al (2011) Absence of effects of Sir2 overexpression on lifespan in C. elegans and Drosophila. Nature 477:482-485.
3. Wood JG et al (2004) Sirtuin activators mimic calorie restriction and delay ageing in metazoans. Nature 430: 686-689.
4. Zhao Y (2016) Nicotinamide for Skin-Cancer Chemoprevention. N Engl J Med 374:789.