Abstract: Cellular senescence is conventionally defined as a state of permanent cell cycle arrest in response to multiple stress factors such as DNA damage but also aging. Excessive accumulation of senescent cells can negatively impact different tissues, creating a proinflammatory environment leading to development of various age-related diseases. This project is focus on the analysis of senescent and senescent-like cells that express a high level of the cell cycle inhibitor gene, p16. Specifically, we found that there is a small but noticeable fraction of mouse oocytes (around 9%) that activate a state of high expression of p16, that normally reflects a strong DNA damage or senescence activation, resulting in irreversible cell cycle arrest. This should be incompatible with fertilization of such oocytes and subsequent embryogenesis. In contrast, we found that p16′ oocytes could be efficiently fertilized and give rise to visually healthy mice. More in depth analysis, revealed that such mice after reaching the adult stage exhibit several abnormalities with most pronounced changed observed in the hematopoietic system. One of them is the fact that these mice in adult stage have a strong reduction in the number of immune cell subsets, resulting in immune system exhaustion. This project aims to unveil the molecular mechanism(s) behind the program activated in p16High oocytes. This program persists across fertilization and remains partially active in adult animals, contributing to lasting phenotypes. My goal
is to identify such lasting phenotypes with the focus on the hematopoietic system.