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Sirtuin Functions in Health and Disease

Institut de Génétique et de Biologie Moléculaire et Cellulaire (H.Y., K.S., J.A.), Centre National de la Recherche Scientifique/Institut National de la Santé et de la Recherche Médicale/Université Louis Pasteur, 67404 Illkirch, France; and Institut Clinique de la Souris (J.A.), 67404 Illkirch, France

Address all correspondence and requests for reprints to: Johan Auwerx, M.D., Ph.D., Institut de Génétique et de Biologie Moléculaire et Cellulaire, 1 Rue Laurent Fries, Boîte Postale 10142, 67404 Illkirch, France. E-mail: auwerx{at}igbmc.u-strasbg.fr.

Sirtuins or Sir2 (silent information regulator 2)-related enzymes have originally been defined as a family of nicotinamide adenine dinucleotide-dependent enzymes that deacetylate lysine residue on various proteins. Certain sirtuins have in addition an ADP-ribosyltransferase activity. The sirtuins are remarkably conserved throughout evolution from archaebacteria to eukaryotes. The mammalian sirtuins SIRT1–SIRT7 are implicated in a variety of cellular functions ranging from gene silencing, over the control of the cell cycle and apoptosis, to energy homeostasis. On a whole-body level, the wide range of cellular activities of the sirtuins suggests that they could constitute therapeutic targets to combat metabolic, neurodegenerative, and proliferative diseases. Here, we review some of the recent data related to the sirtuins and discuss their mode of action, their biological role in cellular and organismal models, and their possible association to age-related human diseases.

NURSA Molecule Pages Link:

Nuclear Receptors:   PPARγ  |  HNF4α  |  AR

Coregulators:   PGC-1  |  Sirt1

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