title: SIRT1 and NAD as regulators of ageing.
abstract: The recent research on ageing processes in mammals throws new light on the biochemistry of circadian clock. The already known regulatory pathways for biological rhythms and metabolism, combined with newly discovered functions of sirtuins, unveil a perspective for new hypotheses, regarding possible links between ageing and circadian rhythms. The NAD World hypothesis - postulated as a systemic regulatory network for the metabolism and ageing, linked with mammalian, NAD+ dependent Sirtuin 1 - conceptually involves two critical elements. One is the systemic, Nampt-controlled NAD+ (nicotinamide phosphoribosyltransferase) biosynthesis, where Nampt (nicotinamide phosphoribosyltransferase) acts as "propulsion" for metabolism and the other is NAD+ dependent deacetylase (SIRT1) - a regulator responsible for various biological effects, depending on its localisation in organism. In this approach, the role of sirtuins, which are evolutionary conservative, NAD+ dependent histone deacetylases, may be very important for the mammalian metabolic clock. This paper is a review of current research on possible links among SIRT1 (Sirtuin 1), metabolism and ageing with particular consideration of the NAD World hypothesis.
authors.affiliation: Leopold Rehan, Department of Internal Medicine, Occupational Diseases and Hypertension, Clinical Centre of Wroclaw Medical University, ul. Borowska 213, 50-556 Wrocław, Poland.
authors.forename: Leopold
authors.initials: L
authors.lastname: Rehan
authors.affiliation: Department of Pathophysiology, Wroclaw Medical University, Poland.
authors.forename: Krystyna
authors.initials: K
authors.lastname: Laszki-Szcząchor
authors.affiliation: Department of Pathophysiology, Wroclaw Medical University, Poland.
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Sobieszczańska
authors.affiliation: Department of Paediatric Nephrology, Wroclaw Medical University, Poland. Electronic address: dorota.polak-jonkisz@umed.wroc.pl.
authors.forename: Dorota
authors.initials: D
authors.lastname: Polak-Jonkisz
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D002940:Circadian Rhythm / Q000502:physiology*; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans; D053858:Metabolic Networks and Pathways / Q000502:physiology*; D008954:Models, Biological; D009243:NAD / Q000096:biosynthesis* / Q000378:metabolism; D054409:Nicotinamide Phosphoribosyltransferase / Q000378:metabolism*; D056564:Sirtuin 1 / Q000378:metabolism*
chemical_list: D009243:NAD; D054409:Nicotinamide Phosphoribosyltransferase; C447939:SIRT1 protein, human; D056564:Sirtuin 1; D006655:Histone Deacetylases
keywords: Ageing; Central metabolic clock; Circadian rhythm; NAD World; NAD+; Nampt; SIRT1; Sirtuins