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.
Keywords: aging; disease modeling; iPSC; induced aging; late-onset disease; neuronal aging; telomerase; telomeres.
Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.