Stem cells possess a unique metabolic landscape that controls their survival and function. The finetuning of redox and metabolic processes is essential for stem cells’ self-renewal, proliferation, and differentiation, which in turn is fundamental to their regenerative capacity. Deviations from this metabolic balance, by contrast, can contribute to ageing and age-associated pathologies, which can particularly impact a person’s quality of life when it is linked to cognitive decline.
It is important to continue deepening our understanding of the ageing brain and the potentially rejuvenating neural stem cells (NSCs) that lie dormant or damaged within. The majority of mammalian NSCs remain in a quiescent state and undergo self-renewal via a slow cell cycle. However, certain stimuli activate these quiescent NSCs causing them to proliferate and differentiate into neurons, astrocytes, or oligodendrocytes depending on the received cue. Metabolite utilization via primary metabolic pathways is a key regulator in the context of NSCs’ survival and regenerative function.
While transcriptional changes have received scholarly attention for many decades, RNA-binding proteins (RBPs) have only recently taken centre stage as regulators of metabolism. RBPs are a versatile group of proteins that can facilitate short- and long-term metabolic adjustments of cells undergoing cell division and differentiation. Furthermore, RBPs can integrate metabolic stimuli through, for example, post-translational modifications, changes in localization or metabolite availability. Our overarching aim is to utilize the metabolically dynamic system of quiescent and activated NSCs during ageing to elucidate the following questions and discover the involvement of canonical and non-canonical RBPs therein:
- What regulates the metabolic alterations that ageing NSCs undergo?
- What role does metabolism play in the ageing process of NSCs?
- What coordinates cytosolic and mitochondrial metabolic pathways in ageing NSCs?