My research is focused on understanding the interaction between senescent cells and cells of the immune system, with particular emphasis on cardiovascular disease. Senescent cells are not “old” or “aged” cells as the name confusingly suggests, but rather represent a change in cell state, much in the same way the cancer cells are not “young” cells because they can proliferate indefinitely.
The senescent state is commonly induced by persistent DNA damage within cells, consequently leading to permanent proliferative arrest. When cells activate this senescent state, they also become immunogenic-meaning they can signal, activate, and be recognised by immune cells. As such, it appears that the senescent state functions to eliminate damaged cells via immunogenic cell death.
Despite the ability of the immune system to destroy senescent cells, they appear to accumulate with age. This accumulation is thought to be due to an age-related decline in immune function leading to inefficient elimination of senescent cells. This means that senescent cells persist in our bodies, constantly secreting proteins that try to communicate with an impaired immune system. However, some of these secreted proteins include pro-inflammatory factors that can damage the surrounding tissues. As such, the accumulation of senescent cells with ageing is thought to promote many age-related pro-inflammatory diseases, including cardiovascular disease. Therefore, the ability to target and eliminate senescent cells through therapeutic strategies (similar to targeting cancer cells) has the potential to alleviate age-related disease and increase health-span- the period of healthy life.
Whilst one way of targeting senescent cells (senotherapeutics) is through the use of drugs, another approach could involve directed elimination of senescent cells by boosting an immune response or preventing its decline. However, very little is known about how senescent cells and immune cells interact with each other, an understanding of which would be greatly beneficial for future research focused on targeting senescent cells.
As such, part of my Marie Curie Fellowship involves investigating the mechanisms by which senescent cells and immune cells interact with each to facilitate immune clearance of senescent cells. My initial focus is on monocytes/macrophages, but as I learn more about immunology and as new findings present themselves, I will likely investigate other immune cells types such as T-cells and Neutrophils. I will keep you updated on my progress.
To learn more about my research subject, check out my review article HERE