There is compelling evidence that senescence drives ageing. The senescence-associated secretory phenotype (SASP) is composed of soluble and small extracellular vesicular (sEV) components, and individual senescent triggers can lead to unique SASP profiles . Therefore, secondary senescence in neighbouring cells can have divergent consequences.
We have preliminary evidence to suggest that proteostasis dysregulation (PD) can trigger senescence. Therefore, this project seek to explore the temporal kinetics of PD in primary senescence initiation, to determine how PD drives secondary senescence in mitotic cells versus post-mitotic neurons, and to explore if PD-driven secondary senescence can be uncoupled from primary senescence using senostatics.
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