Dominick Burton

My current research interests are focused on understanding how senescent cells and immune cells interact with each other to facilitate immune clearance of senescent cells. In particular, I am interested in determining whether immunosenescence contributes to the accumulation of senescent cells in aged and diseased tissues by failing to remove them.

Cellular senescence in non-immune cells such as fibroblasts is characterized by irreversible cell-cycle arrest and the development of an immunogenic phenotype that facilitates self-elimination by the immune system. Senescent cells become immunogenic by secreting chemoattractants for attracting and activating immune cells, expressing intercellular adhesion molecules for binding immune cells and expressing NKG2D ligands that can be recognized by receptors on Natural Killer cells and T-cells. Immunosurveillance of senescent cells facilitates short-term activation of the senescence program that appears to beneficially function in both tumour prevention and wound repair. However, if senescent cells persist in tissues, their pro-inflammatory secretome can induce local tissue damage, thereby promoting age-related disease.

Whilst there has been a correlated increase in the percentage of senescent cells in tissues with age and their presence observed in tissues associated with various age-related diseases, it is not known why senescent cells may accumulate when they are known to be eliminated by the immune system. It has been speculated that immunosenescence, ageing of the immune system, may consequently lead to impaired elimination of senescent cells. If this is indeed the case, then it may suggest that immunosenescence contributes to age-related disease, partly through promoting the accumulation of senescent cells. As such, therapeutically rejuvenating an ageing immune system or preventing its decline could prove beneficial for extending healthspan, the time spent healthy and free from disease.