iPSC-based disease modeling is widely used for studying disorders caused by a single gene mutation (monogenic disorders) that have an early onset39,40, as the approach is ideally suited to such disorders — because iPSCs can be easily derived from patients with these disorders and differentiated into disease-relevant cells, such as neurons. Furthermore, given the relative immaturity of cells differentiated from iPSCs41, there is greater confidence that the phenotypes of cells differentiated from iPSCs provide a good model for diseases with an early onset versus late onset, for which cellular aging may be important in disease pathology41. For example, neurons differentiated from patient iPSCs were used to model spinal muscular atrophy (SMA), an early-onset disease caused by mutations in the gene encoding the survival motor neuron 1 (SMN1)39. Mutations in the SMN1 gene led to degeneration of motor neurons and subsequent muscular atrophy. Type 1 SMA patients usually show symptoms at 6 months from birth, with a rapid disease progression that kills them by the age of two42. In an initial iPSC-based disease modeling study39, iPSCs were derived from fibroblasts of
