title: Genetic modulation of senescent phenotypes in Homo sapiens.
abstract: Single-gene mutations can produce human progeroid syndromes--phenotypes that mimic usual or "normative" aging. These can be divided into two classes--those that have their impacts upon multiple organs and tissues (segmental progeroid syndromes) and those that have their major impacts upon a single organ or tissue (unimodal progeroid syndromes). The prototypic example of the former is the Werner syndrome, a condition caused by mutations of the RecQ family of DNA helicases. Research on the Werner syndrome and a surprising number of other progeroid syndromes support the importance of the maintenance of genomic stability as a partial antidote to aging. The prototypic examples of the latter are Alzheimer type dementias. The three gene products that cause rare autosomal-dominant early-onset varieties of these disorders all participate in the modulation of the beta amyloid precursor protein. They thus support the importance of the maintenance of proper protein processing and folding as a partial antidote to aging.
authors.affiliation: Department of Pathology, University of Washington, Seattle, Washington 98195, USA. gmmartin@u.washington.edu
authors.forename: George M
authors.initials: GM
authors.lastname: Martin
mesh_terms: D000375:Aging / Q000235:genetics* / Q000502:physiology; D000544:Alzheimer Disease / Q000235:genetics / Q000503:physiopathology; D016564:Amyloid beta-Protein Precursor / Q000235:genetics* / Q000378:metabolism; D001260:Ataxia Telangiectasia / Q000235:genetics / Q000503:physiopathology; D003923:Diabetes Mellitus, Lipoatrophic / Q000235:genetics / Q000503:physiopathology; D006801:Humans; D009154:Mutation / Q000235:genetics* / Q000502:physiology; D009223:Myotonic Dystrophy / Q000235:genetics / Q000503:physiopathology; D010641:Phenotype; D011371:Progeria / Q000235:genetics / Q000503:physiopathology; D014898:Werner Syndrome / Q000235:genetics* / Q000503:physiopathology
chemical_list: D016564:Amyloid beta-Protein Precursor