In Huntington's disease (HD), expansion of CAG codons in the huntingtin gene 
(HTT) leads to the aberrant formation of protein aggregates and the differential 
degeneration of striatal medium spiny neurons (MSNs). Modeling HD using 
patient-specific MSNs has been challenging, as neurons differentiated from 
induced pluripotent stem cells are free of aggregates and lack an overt cell 
death phenotype. Here we generated MSNs from HD patient fibroblasts through 
microRNA-based direct neuronal conversion, bypassing the induction of 
pluripotency and retaining age signatures of the original fibroblasts. We found 
that patient MSNs consistently exhibited mutant HTT (mHTT) aggregates, 
mHTT-dependent DNA damage, mitochondrial dysfunction and spontaneous 
degeneration in culture over time. We further provide evidence that erasure of 
age stored in starting fibroblasts or neuronal conversion of presymptomatic HD 
patient fibroblasts results in differential manifestation of cellular phenotypes 
associated with HD, highlighting the importance of age in modeling late-onset 
neurological disorders.