title: Mitochondrial Sirtuins and Molecular Mechanisms of Aging.
abstract: Advancing age is the major risk factor for the development of chronic diseases and is accompanied by changes in metabolic processes and mitochondrial dysfunction. Mitochondrial sirtuins (SIRT3-5) are part of the sirtuin family of NAD+-dependent deacylases and ADP-ribosyl transferases. The dependence on NAD+links sirtuin enzymatic activity to the metabolic state of the cell, poising them as stress sensors. Recent insights have revealed that SIRT3-5 orchestrate stress responses through coordinated regulation of substrate clusters rather than of a few key metabolic enzymes. Additionally, mitochondrial sirtuin function has been implicated in the protection against age-related pathologies, including neurodegeneration, cardiopathologies, and insulin resistance. In this review, we highlight the molecular targets of SIRT3-5 and discuss their involvement in aging and age-related pathologies.
authors.affiliation: Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Robert A H
authors.initials: RAH
authors.lastname: van de Ven
authors.affiliation: Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA; CNC-Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, Portugal.
authors.forename: Daniel
authors.initials: D
authors.lastname: Santos
authors.affiliation: Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA. Electronic address: marcia_haigis@hms.harvard.edu.
authors.forename: Marcia C
authors.initials: MC
authors.lastname: Haigis
mesh_terms: D000375:Aging; D000818:Animals; D034381:Hearing Loss / Q000378:metabolism; D006801:Humans; D008928:Mitochondria / Q000378:metabolism*; D009243:NAD / Q000378:metabolism; D019636:Neurodegenerative Diseases / Q000378:metabolism; D060066:Protein Interaction Maps; D037761:Sirtuins / Q000032:analysis / Q000378:metabolism*; D013312:Stress, Physiological
chemical_list: D009243:NAD; D037761:Sirtuins
keywords: aging; metabolism; mitochondrial sirtuins; sirtuin networks; stress response