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.
Vera, E., Bosco, N., & Studer, L. (2016). Generating Late-Onset Human iPSC-Based Disease Models by Inducing Neuronal Age-Related Phenotypes through Telomerase Manipulation. Cell Reports, 17(4), 1184–1192. https://doi.org/10.1016/j.celrep.2016.09.062