The silent information regulator (SIR) genes code for a highly conserved family of proteins from bacteria to mammals – sirtuins. Sirtuins are NAD+-dependent protein deacetylases with diverse physiological functions relating to cell survival, inflammation, energy metabolism, cancer. They are a part of complicated biological response system that influences many other regulator molecules and pathways. Sirtuins respond in an epigenetic manner to a variety of environmental factors, such as: dietary, lifestyle, toxins, etc. The data on the importance of vitamin B3 in supporting the sirtuin enzyme activity and a role of nicotinamide in inhibiting this activity are summarized. This mode of regulation may be exploited to manipulate the sirtuins activity in the context of various pathological conditions.