Tracing Mitochondrial Marks of Neuronal Aging in iPSCs-Derived Neurons and Directly Converted Neurons - Data

This study aimed to determine if neurons derived from induced pluripotent stem cells (iPSCsNs) and directly converted neurons (iNs) from the same source cells exhibit changes in mitochondrial properties related to aging. This research addresses the uncertainty around whether aged iPSCsNs retain aging-associated mitochondrial impairments upon transitioning through pluripotency while direct conversion maintains these impairments. We found that both aged models exhibited characteristics of aging, such as decreased ATP, mitochondrial membrane potential, respiration, NAD+/NADH ratio, and increased radicals and mitochondrial mass. In addition, both neuronal models showed a fragmented mitochondrial network. However, aged iPSCsNs did not exhibit a metabolic shift towards glycolysis, unlike aged iNs. Furthermore, mRNA expression differed significantly between aged iPSCsNs and aged iNs. The study concludes that aged iPSCsNs may differ in transcriptomics and the aging-associated glycolytic shift but can be a valuable tool for studying specific feature of mitochondrial neuronal aging in vitro alongside aged iNs.