title: Molecular bases of progeroid syndromes.
abstract: Progeroid syndromes (PSs) constitute a group of disorders characterized by clinical features mimicking physiological aging at an early age. In some of these syndromes, biological hallmarks of aging are also present, whereas in others, a link with physiological aging, if any, remains to be elucidated. These syndromes are clinically and genetically heterogeneous and most of them, including Werner syndrome and Hutchinson-Gilford progeria, are known as 'segmental aging syndromes', as they do not feature all aspects usually associated to physiological aging. However, all the characterized PSs enter in the field of rare monogenic disorders and several causative genes have been identified. These can be separated in subcategories corresponding to (i) genes encoding DNA repair factors, in particular, DNA helicases, and (ii) genes affecting the structure or post-translational maturation of lamin A, a major nuclear component. In addition, several animal models featuring premature aging have abnormal mitochondrial function or signal transduction between membrane receptors, nuclear regulatory proteins and mitochondria: no human pathological counterpart of these alterations has been found to date. In recent years, identification of mutations and their functional characterization have helped to unravel the cellular processes associated to segmental PSs. Recently, several studies allowed to establish a functional link between DNA repair and A-type lamins-associated syndromes, evidencing a relation between these syndromes, physiological aging and cancer. Here, we review recent data on molecular and cellular bases of PSs and discuss the mechanisms involved, with a special emphasis on lamin A-associated progeria and related disorders, for which therapeutic approaches have started to be developed.
authors.affiliation: Inserm U491, Génétique Médicale et Développement, Université de la Méditerranée, Faculté de Médecine, 13385 Marseille Cedex 05, France.
authors.forename: Claire L
authors.initials: CL
authors.lastname: Navarro
authors.forename: Pierre
authors.initials: P
authors.lastname: Cau
authors.forename: Nicolas
authors.initials: N
authors.lastname: Lévy
mesh_terms: D000328:Adult; D002648:Child; D003057:Cockayne Syndrome / Q000209:etiology / Q000235:genetics / Q000503:physiopathology; D004260:DNA Repair / Q000235:genetics; D006801:Humans; D034904:Lamin Type A / Q000235:genetics; D000071518:Liver X Receptors; D008928:Mitochondria / Q000378:metabolism; D008954:Models, Biological; D008957:Models, Genetic; D057093:Orphan Nuclear Receptors; D011371:Progeria / Q000209:etiology / Q000235:genetics* / Q000503:physiopathology; D053484:RecQ Helicases / Q000235:genetics; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics; D013577:Syndrome; D014898:Werner Syndrome / Q000209:etiology / Q000235:genetics / Q000503:physiopathology
chemical_list: D034904:Lamin Type A; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D018160:Receptors, Cytoplasmic and Nuclear; D053484:RecQ Helicases