Modeling diseases that have a late onset is more challenging, because cells differentiated from human iPSCs in general exhibit fetal-like properties41. However, induced cellular aging has been used to aid in successful modeling of late-onset diseases43–46. One way to induce aging in cells differentiated from human iPSCs is to treat cells with cellular stressors, including compounds that target mitochondrial function or protein degradation, such as pyraclostrobin and MG-13243,44,46,47. Another way to induce cellular aging is to ectopically express gene products that induce premature aging, such as progerin45. However, whether cellular stressors or progerin expression can elicit cellular aging through a mechanism that is similar to normal aging remains to be determined41. Moreover, recent studies indicate that cellular maturation and aging may be distinct events41,48. It remains unclear whether the cellular aging inducers can promote both cellular maturation and aging, as opposed to triggering cellular aging in immature cells48. Alternatively, the direct reprogramming approach that involves direct conversion of human fibroblasts into other lineage-specific cells, such as neurons, does not erase cellular aging markers49. Indeed, neurons derived from aged fibroblasts through
