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Senescent endothelial cells promote the accumulation of pathogenic perivascular mast cells in ageing tissues

Code: BC-DTP_2026_31

Title: Senescent endothelial cells promote the accumulation of pathogenic perivascular mast cells in ageing tissues

Primary Supervisor: Loic Rolas

Email: l.rolas@qmul.ac.uk

Institute: Wolfson Institute of Population Health

Secondary Supervisor: Mathieu-Benoit Voisin

Email: m.b.voisin@qmul.ac.uk

Institute: Wolfson Institute of Population Health

Lay Summary:

As people live longer, the number of older adults continues to rise, placing growing pressure on healthcare systems. Many age-related diseases are linked to the decline of the cardiovascular system, which supplies the body with oxygen, nutrients and immune support. Immune cells located near blood vessels, such as mast cells, help maintain healthy tissues by regulating blood flow and supporting repair. Ageing disrupts these processes and increases vulnerability to disease. A major driver of this decline is cellular senescence, a state in which cells stop dividing and release large amounts of inflammatory molecules. When endothelial cells, which form the inner lining of all blood vessels, become senescent, they can impair vessel function and affect neighbouring cells. It remains unclear whether senescent endothelial cells influence mast cell behaviour, and this question is central to the research. Using advanced microscopy, we have found that mast cell numbers increase in aged tissues, particularly near senescent endothelial cells. This rise appears to be linked to leakier blood vessels during inflammation, which leads to tissue damage. The project will investigate how senescent endothelial cells drive mast cell accumulation and activation, and how these interactions contribute to age-related disease. The analysis will focus on mast cells in a mouse model of early endothelial cell senescence and human tissues to uncover the mechanisms and consequences for conditions common in older adults, such as ischaemia-reperfusion injury. This work will advance our understanding of vascular ageing and help identify new approaches to treat age-related cardiovascular disease. 

Aims:

AIM 1: To quantify the numbers and localisation of MCs in relation to EC senescence. (Year 1)

AIM 2: To investigate the mechanisms through which EC senescence promotes increased MC number.  (Year 2)

AIM3: To investigate the activation state of mast cell in senescent mouse and  human vasculature. (Year 3)

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