When rejuvenation is a problem: challenges of modeling late-onset neurodegenerative disease

In contrast to the successful modeling of early-onset disorders using patient-specific cells, modeling of late-onset neurodegenerative diseases such as Parkinson's disease remains a challenge. This might be related to the often ignored fact that current induced pluripotent stem cell (iPSC) differentiation protocols yield cells that typically show the behavior of fetal stage cells. Acknowledging aging as a contributing factor in late-onset neurodegenerative disorders represents an important step on the road towards faithfully recreating these diseases in vitro. Here, we summarize progress in the field and review the strategies and challenges for triggering late-onset disease phenotypes.