Exploring the impact of partial reprogramming on astrocyte biology and its implications for brain homeostasis and aging

In order to address the limited regenerative capacity of the mammalian brain and the challenges posed by aging-related neurological disorders, we harness reprogramming technology, focusing specifically on neural cell rejuvenation through transient expression of the 4 Yamanaka Factors (4Fs). As the brain ages and undergoes cognitive decline, homeostatic loss and neuroinflammation, our project focuses on the potential of partial reprogramming (PR) to reshape the epigenetic landscape, offering a promising avenue for cellular rejuvenation. We focus primarily on astrocytes, fundamental cells that control central nervous system homeostasis, with crucial roles in neuroprotection, immune response and aging-associated processes. Through a comprehensive analysis including quantification of age-related epigenetic markers, measurements of cellular metabolism and assessment of nuclear envelope erosion, we aim to unravel the impact of partial reprogramming in astrocytes. Promisingly, our in vivo experiments demonstrate robust improvements in motor function, spatial memory and recognition memory following RP treatment. We propose that rejuvenation-by-reprogramming of brain cells could have therapeutic potential to modify the course of aging and thereby reduce disease susceptibility in the central nervous system.