Catalyst Awardee

Project Description

Investigating the Mechanisms of Age Dependent Decline in the Immunosurveillance of Senescent Cells by Natural Killer Cells

Amit Sharma, Ph.D. | SENS Research Foundation; and Judith Campisi, Ph.D. | Buck Institute
Competition Sponsor: National Academy of Medicine
Awardee Year: 2020

Senescent cells are characterized by an irreversible arrest of the cell cycle and secrete a milieu of pro-inflammatory cytokines, chemokines, and growth factors collectively referred to as the Senescence-Associated Secretory Phenotype (SASP) due to which these cells have been implicated in a large number of age-related diseases, and recent efforts to develop therapeutic interventions are centered around either selectively eliminating senescent cells (senolytics) or by reducing secretion of inflammatory factors from these cells (senomorphic) While these approaches present possible avenues for reducing the impact of senescent cells, they still lack specificity. Innate immune cells like Natural Killer (NK) cells can selectively eliminate senescent cells, thus providing another avenue for removal of senescent cells. However, a lack of understanding as to how aging influences the specificity and sensitivity of NK cell to target senescent cells is a major hurdle in realizing potential therapy. Based on our preliminary data from FACS analysis of blood samples of healthy human subjects, we hypothesize that NK cell functions decline with age, and as a consequence senescent cells accumulate faster in aged organisms. Our animal experiments demonstrate that blood (including young NK cells) transferred from young mice to old mice drastically reduces senescent cell burden in older mice. The central aim of the proposed project is to determine if the NK cells lose their ability to selectively target senescent cells and if this can be restored. We would use ex vivo and mouse model to test if these ‘activated’ NK cells improve various markers of health-span.

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View this project poster, first displayed at the 2021 Global Innovator Summit.

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