title: Klotho modulates the stress response in human senescent endothelial cells.
abstract: Lack of Klotho expression in mice leads to premature aging and age-related diseases, including vascular diseases. The aim of this study was to determine how endothelial cell line senescence affects Klotho expression and whether intra- or extracellular Klotho has any effect on the response of senescent cells to oxidative stress. The study was performed using human endothelial cells (HUVEC); cell aging was obtained by prolongation of cell division to 42 population doublings (PD). Senescence was also obtained by exposure to TNFα, which causes cell changes resembling cellular senescence. The decline in Klotho preceded the manifestations of cell ageing: telomere shortening and β-galactosidase expression. Klotho was also reduced in cells exposed to the proinflammatory cytokine TNFα. The addition of exogenous Klotho to aging cells did not modify the proportion of cells with short telomeres or any other feature of cell aging; however, exogenous Klotho prevented the changes resembling premature cellular senescence associated with TNFα, such as the decrease in telomere length and the increase in β-galactosidase-positive cells. Likewise exogenous Klotho prevented the increases in reactive oxygen species (ROS) activity, mitochondrial potential and cell apoptosis induced by TNFα.
authors.affiliation: Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC)/Fundación de Investigaciones Biomédicas de Córdoba (FIBICO), Reina Sofía University Hospital, Córdoba, Spain. julia.carracedo.exts@juntadeandalucia.es
authors.forename: Julia
authors.initials: J
authors.lastname: Carracedo
authors.forename: Paula
authors.initials: P
authors.lastname: Buendía
authors.forename: Ana
authors.initials: A
authors.lastname: Merino
authors.forename: Juan Antonio
authors.initials: JA
authors.lastname: Madueño
authors.forename: Esther
authors.initials: E
authors.lastname: Peralbo
authors.forename: Alberto
authors.initials: A
authors.lastname: Ortiz
authors.forename: Alejandro
authors.initials: A
authors.lastname: Martín-Malo
authors.forename: Pedro
authors.initials: P
authors.lastname: Aljama
authors.forename: Mariano
authors.initials: M
authors.lastname: Rodríguez
authors.forename: Rafael
authors.initials: R
authors.lastname: Ramírez
mesh_terms: D000375:Aging; D000818:Animals; D049109:Cell Proliferation; D016922:Cellular Senescence; D042783:Endothelial Cells / Q000166:cytology*; D005786:Gene Expression Regulation; D005966:Glucuronidase / Q000378:metabolism*; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D000090265:Klotho Proteins; D008297:Male; D018384:Oxidative Stress; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species; D016615:Telomere / Q000648:ultrastructure; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D001616:beta-Galactosidase / Q000378:metabolism
chemical_list: D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D001616:beta-Galactosidase; D005966:Glucuronidase; D000090265:Klotho Proteins