title: Generating Late-Onset Human iPSC-Based Disease Models by Inducing Neuronal Age-Related Phenotypes through Telomerase Manipulation.
abstract: Modeling late-onset disorders such as Parkinson's disease (PD) using iPSC technology remains a challenge, as current differentiation protocols yield cells with the properties of fetal-stage cells. Here, we tested whether it is possible to accelerate aging in vitro to trigger late-onset disease phenotypes in an iPSC model of PD. In order to manipulate a factor that is involved in natural aging as well as in premature aging syndromes, we used telomere shortening as an age-inducing tool. We show that shortened telomeres result in age-associated as well as potentially disease-associated phenotypes in human pluripotent stem cell (hPSC)-derived midbrain dopamine (mDA) neurons. Our approach provides proof of concept for the further validation of telomere shortening as an induced-aging tool for late-onset-disease modeling.
authors.affiliation: Center for Stem Cell Biology, Sloan-Kettering Institute, 1275 York Ave., New York, NY 10065, USA; Developmental Biology Program, Sloan-Kettering Institute, 1275 York Ave., New York, NY 10065, USA. Electronic address: verae@mskcc.org.
authors.forename: Elsa
authors.initials: E
authors.lastname: Vera
authors.affiliation: Laboratory for Cell Biology and Genetics, The Rockefeller University, 1230 York Avenue, Box 159, New York, NY 10065, USA.
authors.forename: Nazario
authors.initials: N
authors.lastname: Bosco
authors.affiliation: Center for Stem Cell Biology, Sloan-Kettering Institute, 1275 York Ave., New York, NY 10065, USA; Developmental Biology Program, Sloan-Kettering Institute, 1275 York Ave., New York, NY 10065, USA.
authors.forename: Lorenz
authors.initials: L
authors.lastname: Studer
mesh_terms: D000375:Aging / Q000473:pathology*; D000818:Animals; D002454:Cell Differentiation; D004195:Disease Models, Animal; D015536:Down-Regulation; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism / Q000473:pathology*; D010641:Phenotype; D019098:Telomerase / Q000378:metabolism*; D016615:Telomere / Q000378:metabolism
chemical_list: D019098:Telomerase
keywords: aging; disease modeling; iPSC; induced aging; late-onset disease; neuronal aging; telomerase; telomeres