title: Model of human aging: recent findings on Werner's and Hutchinson-Gilford progeria syndromes.
abstract: The molecular mechanisms involved in human aging are complicated. Two progeria syndromes, Werner's syndrome (WS) and Hutchinson-Gilford progeria syndrome (HGPS), characterized by clinical features mimicking physiological aging at an early age, provide insights into the mechanisms of natural aging. Based on recent findings on WS and HGPS, we suggest a model of human aging. Human aging can be triggered by two main mechanisms, telomere shortening and DNA damage. In telomere-dependent aging, telomere shortening and dysfunction may lead to DNA damage responses which induce cellular senescence. In DNA damage-initiated aging, DNA damage accumulates, along with DNA repair deficiencies, resulting in genomic instability and accelerated cellular senescence. In addition, aging due to both mechanisms (DNA damage and telomere shortening) is strongly dependent on p53 status. These two mechanisms can also act cooperatively to increase the overall level ofgenomic instability, triggering the onset of human aging phenotypes.
authors.affiliation: Department of Nursing, Kang-Ning Junior College of Medical Care and Management,Taipei,Taiwan. slding@knjc.edu.tw
authors.forename: Shian-Ling
authors.initials: SL
authors.lastname: Ding
authors.forename: Chen-Yang
authors.initials: CY
authors.lastname: Shen
mesh_terms: D000368:Aged; D000375:Aging / Q000235:genetics* / Q000378:metabolism; D004247:DNA / Q000235:genetics; D005090:Exodeoxyribonucleases / Q000235:genetics / Q000378:metabolism; D006801:Humans; D034904:Lamin Type A / Q000235:genetics / Q000378:metabolism; D008060:Lipodystrophy; D008958:Models, Molecular; D009154:Mutation; D011371:Progeria / Q000235:genetics* / Q000378:metabolism; D053484:RecQ Helicases / Q000235:genetics / Q000378:metabolism; D014898:Werner Syndrome / Q000235:genetics* / Q000378:metabolism; D000071657:Werner Syndrome Helicase
chemical_list: C494847:LMNA protein, human; D034904:Lamin Type A; D004247:DNA; D005090:Exodeoxyribonucleases; D053484:RecQ Helicases; C098785:WRN protein, human; D000071657:Werner Syndrome Helicase