title: Accelerated aging syndromes, are they relevant to normal human aging?
abstract: Hutchinson-Gilford Progeria (HGPS) and Werner syndromes are diseases that clinically resemble some aspects of accelerated aging. HGPS is caused by mutations in theLMNA gene resulting in post-translational processing defects that trigger Progeria in children. Werner syndrome, arising from mutations in the WRN helicase gene, causes premature aging in young adults. What are the molecular mechanism(s) underlying these disorders and what aspects of the diseases resemble physiological human aging? Much of what we know stems from the study of patient derived fibroblasts with both mutations resulting in increased DNA damage, primarily at telomeres. However, in vivo patients with Werner's develop arteriosclerosis, among other pathologies. In HGPS patients, including iPS derived cells from HGPS patients, as well as some mouse models for Progeria, vascular smooth muscle (VSM) appears to be among the most severely affected tissues. Defective Lamin processing, associated with DNA damage, is present in VSM from old individuals, indicating processing defects may be a factor in normal aging. Whether persistent DNA damage, particularly at telomeres, is the root cause for these pathologies remains to be established, since not all progeroid Lmna mutations result in DNA damage and genome instability.
authors.affiliation: Institute of Medical Biology, 8A Biomedical Grove, #06-06 Immunos, 138648 Singapore.
authors.forename: Oliver
authors.initials: O
authors.lastname: Dreesen
authors.forename: Colin L
authors.initials: CL
authors.lastname: Stewart
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D002648:Child; D004249:DNA Damage; D004195:Disease Models, Animal; D005090:Exodeoxyribonucleases / Q000235:genetics; D042822:Genomic Instability; D006801:Humans; D034904:Lamin Type A / Q000235:genetics; D051379:Mice; D009154:Mutation; D011371:Progeria / Q000235:genetics / Q000503:physiopathology*; D053484:RecQ Helicases / Q000235:genetics; D014898:Werner Syndrome / Q000235:genetics / Q000503:physiopathology*; D000071657:Werner Syndrome Helicase; D055815:Young Adult
chemical_list: D034904:Lamin Type A; D005090:Exodeoxyribonucleases; D053484:RecQ Helicases; C098785:WRN protein, human; D000071657:Werner Syndrome Helicase