Uncovering the role of proteostasis dysregulation in primary and secondary senescence

Cleo Bishop (primary)
Blizard Institute
Barts and The London School of Medicine and Dentistry, Queen Mary University of London
Kei Cho (secondary)
Basic and Clinical Neuroscience
Institute of Psychiatry, Psychology and Neuroscience, King’s College London


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 [1]. 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.


1. Gorgoulis et al., Cellular Senescence: Defining a Path Forward (2019) Cell 179(4): 813-827.
2. Wallis et al., Isolation methodology is essential to the evaluation of the extracellular vesicle component of the senescence-associated secretory phenotype (2021) Journal of Extracellular Vesicles In press.
3. Avelar et l., A multidimensional systems biology analysis of cellular senescence in aging and disease (2020) Genome Biology 21: 91-94.
4. Wallis et al., The bright and dark side of extracellular vesicles in the senescence-associated secretory phenotype (2020) Mech. Ageing Dev. 189:111263.
5. Regan et al., Tau phosphorylation at serine 396 residue is required for hippocampal LTD (2015) J Neurosci 35: 4804-4812.

Genes, development and STEM* approaches to biology
Area of Biology
Techniques & Approaches
BioinformaticsImage ProcessingMicroscopy / ElectrophysiologyMolecular Biology