title: Genetic alterations in accelerated ageing syndromes. Do they play a role in natural ageing?
abstract: The molecular mechanisms leading to human senescence are still not known mostly because of the complexity of the process. Different research approaches are used to study ageing including studies of monogenic segmental progeroid syndromes. None of the known progerias represents true precocious ageing. Some of them, including Werner (WS), Bloom (BS), and Rothmund-Thomson syndromes (RTS) as well as combined xeroderma pigmentosa-Cockayne syndrome (XP-CS) are characterised by features resembling precocious ageing and the increased risk of malignant disease. Such phenotypes result from the mutations of the genes encoding proteins involved in the maintenance of genomic integrity, in most cases DNA helicases. Defective functioning of these proteins affects DNA repair, recombination, replication and transcription. Other segmental progeroid syndromes, such as Hutchinson-Gilford progeria (HGPS) and Cockayne syndrome are not associated with an increased risk of cancer. In this paper we present the clinical and molecular features of selected progeroid syndromes and describe the potential implications of these data for studies of ageing and cancer development.
authors.affiliation: Department of Endocrinology, Medical Research Center, Polish Academy of Sciences, 1a Banacha Street, 02-097 Warsaw, Poland. monika@amwaw.edu.pl
authors.forename: Monika
authors.initials: M
authors.lastname: Puzianowska-Kuznicka
authors.forename: Jacek
authors.initials: J
authors.lastname: Kuznicki
mesh_terms: D000375:Aging / Q000235:genetics*; D019588:Aging, Premature / Q000235:genetics*; D001816:Bloom Syndrome / Q000209:etiology / Q000235:genetics; D003057:Cockayne Syndrome / Q000209:etiology / Q000235:genetics; D006801:Humans; D011371:Progeria / Q000209:etiology / Q000235:genetics; D011038:Rothmund-Thomson Syndrome / Q000209:etiology / Q000235:genetics; D014898:Werner Syndrome / Q000209:etiology / Q000235:genetics