Project

The interaction and clearance of senescent vascular cells by the innate immune system

Goal: Cell senescence plays a paradoxical but important role in physiology; it protects organisms against cancer but also contributes to age-related loss of tissue function. Senescent cells accumulate during ageing, particularly at sites of age-related pathologies such as vascular tissue, contributing to fibrotic cardiovascular disease. Therefore, the aim of this research is to understand why senescent cells accumulate later in life for the purpose of identifying potential therapeutic strategies for eliminating senescent cells. This project, founded in an emerging field of ageing research, will determine the interaction and clearance of senescent cells by ageing innate immune cells.

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Dominick G.A Burton
added a research item
In response to persistent DNA damage, induction into cell senescence promotes an immunogenic program which facilitates immune clearance of these damaged cells. Under physiological conditions, senescent cells can activate both innate and adaptive immune responses, functioning to maintain tissue homeostasis. In addition, emerging findings suggest that programmed induction of cell senescence may be important for regulating reproductive processes, partly facilitated by immune clearance. However, likely owing to ageing of the immune system, a failure to eliminate senescent cells can contribute to their persistence in tissues, leading to the development and progression of age-related diseases. Such immune failure may in part be due to activation of the senescence program in immune cells, leading to their dysfunction. Furthermore, senescent cells under certain biological contexts have been shown to instead promote immune suppression, a response that may reflect differences between an acute verses chronic senescent phenotype. In this review, we provide an overview of the research to date concerning senescence immunosurviellance, including a focused discussion on the mechanisms by which macrophages may recognise senescent cells. Senescence immunotherapy strategies as an alternative to senolytics for the removal of senescent cells will also be discussed.
Dominick G.A Burton
added an update
Currently writing a paper on the role of an acute and chronic senescent secretome on monocyte/macrophage function.
 
Dominick G.A Burton
added a project goal
Cell senescence plays a paradoxical but important role in physiology; it protects organisms against cancer but also contributes to age-related loss of tissue function. Senescent cells accumulate during ageing, particularly at sites of age-related pathologies such as vascular tissue, contributing to fibrotic cardiovascular disease. Therefore, the aim of this research is to understand why senescent cells accumulate later in life for the purpose of identifying potential therapeutic strategies for eliminating senescent cells. This project, founded in an emerging field of ageing research, will determine the interaction and clearance of senescent cells by ageing innate immune cells.