title: AMPK and SIRT1: a long-standing partnership?
abstract: AMP-activated protein kinase (AMPK) and the histone/protein deacetylase SIRT1 are fuel-sensing molecules that have coexisted in cells throughout evolution. When a cell's energy state is diminished, AMPK activation restores energy balance by stimulating catabolic processes that generate ATP and downregulating anabolic processes that consume ATP but are not acutely needed for survival. SIRT1 in turn is best known historically for producing genetic changes that mediate the increase in longevity caused by calorie restriction. Although the two molecules have been studied intensively for many years, only recently has it become apparent that they have similar effects on diverse processes such as cellular fuel metabolism, inflammation, and mitochondrial function. In this review we will examine the evidence that these similarities occur because AMPK and SIRT1 both regulate each other and share many common target molecules. In addition, we will discuss the clinical relevance of these interactions and in particular the possibility that their dysregulation predisposes to disorders such as type 2 diabetes and atherosclerotic cardiovascular disease and is a target for their therapy.
authors.affiliation: Departments of Medicine, Physiology, and Biophysics, Boston University School of Medicine and Boston Medical Center, Boston, Massachusetts 02118, USA. nrude@bu.edu
authors.forename: Neil B
authors.initials: NB
authors.lastname: Ruderman
authors.forename: X Julia
authors.initials: XJ
authors.lastname: Xu
authors.forename: Lauren
authors.initials: L
authors.lastname: Nelson
authors.forename: José M
authors.initials: JM
authors.lastname: Cacicedo
authors.forename: Asish K
authors.initials: AK
authors.lastname: Saha
authors.forename: Fan
authors.initials: F
authors.lastname: Lan
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Ido
mesh_terms: D000818:Animals; D017868:Cyclic AMP-Dependent Protein Kinases / Q000235:genetics / Q000502:physiology*; D003924:Diabetes Mellitus, Type 2 / Q000201:enzymology; D004734:Energy Metabolism / Q000502:physiology*; D004789:Enzyme Activation / Q000502:physiology; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D056564:Sirtuin 1 / Q000235:genetics / Q000502:physiology*
chemical_list: D017868:Cyclic AMP-Dependent Protein Kinases; C447939:SIRT1 protein, human; D056564:Sirtuin 1