Telomere shortening in hiPSCs results in neuronal and astrocyte aging

Telomerase reverse transcriptase (TERT) plays a crucial role in maintaining telomere length, which are specialised protective caps at the end of chromosomes. The lack of in vitro aging models, particularly for the central nervous system (CNS), has impeded progress in understanding aging and age-associated neurodegenerative diseases. In this study, we aimed to explore the possibility of accelerating aging in vitro using hiPSC (human induced pluripotent stem cell) technology. To achieve this, we utilised CRISPR/Cas9 to generate TERT loss-of-function hiPSCs, resulting in a loss of telomerase function and shortened telomeres. Through directed differentiation, we generated motor neurons and astrocytes to investigate whether telomere shortening could lead to age-associated phenotypes in CNS cell types. RNA-seq analysis of neural progenitor cells, astrocytes and motor neurons speciments obtained either from wild type human induced pluripotent stem cells (hiPSC) or from hi PSCs with TERT loss-of-function generated via the CRISPR/Cas9 technology.