title: Sirtuin function in aging heart and vessels.
abstract: Age is the most important risk factor for metabolic alterations and cardiovascular accidents. Although class III histone deacetylases, alias Sirtuins, have been appealed as "the fountain of youth" their role in longevity control and prevention of aging-associated disease is still under debate. Indeed, several lines of evidence indicate that sirtuin activity is strictly linked to metabolism and dependent on NAD(+) synthesis both often altered as aging progresses. During aging the cardiovascular system is attacked by a variety of environmental stresses, including those determined by high blood glucose and lipid levels, or by the presence of oxidized lipoproteins which, among others, determine important oxidative stress signals. In such a milieu, heart and vessels develop a functional impairment leading to atherosclerosis, ischemia, heart insufficiency and failure. Sirtuins, which are believed to have a positive impact on cardiovascular physiology and physiopathology, are distributed in different subcellular compartments including the nucleus, the cytoplasm and the mitochondria, where they regulate expression and function of a large variety of target genes and proteins. Remarkably, experimental animal models indicate resveratrol, the first natural compound described to positively regulate the activity of sirtuins, as able to protect the endothelium and the heart exposed to a variety of stress agents. This review will focus on the regulation and function of mammalian sirtuins with special attention paid to their role as cardiovascular "defenders" giving indication of their targets of potential relevance for the development of future therapeutics. This article is part of a Special Issue entitled CV Aging.
authors.affiliation: Division of Cardiovascular Epigenetics, Department of Cardiology, Goethe University, Frankfurt am Main 60596, Germany. Electronic address: pitini@hotmail.it.
authors.forename: Chiara
authors.initials: C
authors.lastname: Cencioni
authors.affiliation: Division of Cardiovascular Epigenetics, Department of Cardiology, Goethe University, Frankfurt am Main 60596, Germany. Electronic address: fspallotta@gmail.com.
authors.forename: Francesco
authors.initials: F
authors.lastname: Spallotta
authors.affiliation: Pasteur Institute - Cenci-Bolognetti Foundation, Department of Drug Chemistry and Technologies, Sapienza University of Rome, Rome, Italy. Electronic address: antonello.mai@gmail.com.
authors.forename: Antonello
authors.initials: A
authors.lastname: Mai
authors.affiliation: Molecular Cardiology Laboratory, IRCCS-Policlinico San Donato, San Donato Milanese, Milan 20,097, Italy. Electronic address: fabio.martelli@grupposandonato.it.
authors.forename: Fabio
authors.initials: F
authors.lastname: Martelli
authors.affiliation: Consiglio Nazionale delle Ricerche, Istituto di Biologia Cellulare e Neurobiologia, Roma, Italy. Electronic address: afarsetti@gmail.com.
authors.forename: Antonella
authors.initials: A
authors.lastname: Farsetti
authors.affiliation: Internal Medicine Clinic III, Department of Cardiology, Goethe University, Frankfurt am Main 60,596, Germany. Electronic address: zeiher@em.uni-frankfurt.de.
authors.forename: Andreas M
authors.initials: AM
authors.lastname: Zeiher
authors.affiliation: Division of Cardiovascular Epigenetics, Department of Cardiology, Goethe University, Frankfurt am Main 60596, Germany. Electronic address: gaetano@em.uni-frankfurt.de.
authors.forename: Carlo
authors.initials: C
authors.lastname: Gaetano
mesh_terms: D000375:Aging / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D001808:Blood Vessels / Q000378:metabolism / Q000473:pathology; D002316:Cardiotonic Agents / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology; D005786:Gene Expression Regulation; D006333:Heart Failure / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008928:Mitochondria / Q000378:metabolism* / Q000473:pathology; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D018384:Oxidative Stress; D015398:Signal Transduction; D037761:Sirtuins / Q000145:classification / Q000235:genetics / Q000378:metabolism*
chemical_list: D002316:Cardiotonic Agents; D037761:Sirtuins
keywords: Acetylation; Aging; Endothelium; Metabolism; Myocardium; Sirtuins