Sequelae and reversal of age-dependent alterations in mitochondrial dynamics via autophagy enhancement in reprogrammed human neurons.

ABSTRACT: How aging of human neurons affects dynamics of essential organelle such as mitochondria and autophagosomes remains largely unknown. MicroRNA-induced directly reprogrammed neurons (miNs) derived from adult fibroblasts retain age-associated signatures of the donor, enabling the study of age-dependent features in human neurons, including longitudinal isogenic samples. Transcriptomic analysis revealed that neurons derived from elderly individuals are characterized by gene expression changes associated with the regulation of autophagosomes, lysosomes, and mitochondria, compared to young counterparts. To clarify these changes at the cellular level, we performed live-cell imaging of cellular organelles in miNs from donors of different ages. Older donor miNs exhibit decreased mitochondrial membran

SUBMITTER: Klinman E 

PROVIDER: S-EPMC12621752 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature