Grant: Catalyst Grant: Pilot Projects in Aging - Biological & Clinical Aspects of Aging

Cellular senescence or cell aging prevents the proliferation of damaged cells and is an essential mechanism to suppress cancer. Senescent cells can persist for extended periods and can modify their microenvironment. It is proposed that their accumulation can alter tissue functions to favor age-associated pathologies such as inflammation and cancer. The rate of accumulation of senescent cells in aging tissues or following cancer therapy is believe to result from the balance between their appearance and clearance. Senescent cells can contribute to tissue dysfunction by actively secreting factors that creates a pro-inflammatory milieu. Interestingly, previous studies have suggested an important role for white blood cells such as the natural killers for the clearance of senescent cells. However, the contribution of other important white blood cells such as the macrophages has not been well explored yet. Macrophages can be pro-inflammatory leading to more tissue destruction or anti-inflammatory to promote tissue repair. The local environment or milieu will affect how they will become. Also, they can ingest various forms of dead cells. The influence of factors secreted by senescent cells on macrophage functions and their contribution in senescent cell clearance are ill defined. In this project, we propose to study how senescent cells can influence the macrophages and if the macrophages are important in aged cell killing and clearance. This knowledge will provide crucial insights into the pro-inflammatory nature of aging-related diseases such as cancer. This information could lead to the development of new forms of therapies to promote an ordered resolution of the inflammation associated with aging.