SENESCENCE CLEARANCE (256451)

  https://cordis.europa.eu/project/id/256451

  FP7 (2007-2013)

  Mechanisms of immune surveillance of senescent cells

  Marie Curie Action: "Reintegration Grants" (FP7-PEOPLE-2009-RG)

  immunology  ·  oncology  ·  RNA

  2010-07-01 Start Date (YY-MM-DD)

  2014-06-30 End Date (YY-MM-DD)

  € 100,000 Total Cost

  Description

Cellular senescence, a stable form of cell cycle arrest, is a mechanism limiting the proliferative potential of cells. Recent studies demonstrate that cellular senescence imposes a potent barrier to tumorigenesis and contributes to the cytotoxicity of certain anticancer agents. In addition to sites of persistent damage and precancerous lesions, senescent cells have also been observed in tissues of aged individuals and can contribute to decline of tissue function with age. Therefore, mechanisms responsible for control over presence of senescent cells play central role in cancer prevention and aging. In my post-doctoral training I was first to demonstrate that cellular senescence protects against liver fibrosis, and that senescent cells can be cleared by the innate immune system to insure return to the pre-damage state. Components of the innate immune system, macrophages and NK cells were also demonstrated to clear senescent cell from tumors. However, molecular mechanisms of the recognition and the killing of senescent cells remain to be understood. Therefore, I propose to study contribution of NK cells and macrophages to recognition and elimination of senescent cells. Molecular mechanisms responsible for these interactions will be studied using engineered cell lines were senescence can be induced. Elaborate short hairpin RNA techniques will allow discovery of genes in senescent cells that are responsible for signaling to immune cells from one side, and from the other side identification of molecules in immune cells that can contribute to senescent cell elimination. Uncovering the mechanisms of interaction of senescent cells with the immune system will reveal the role of these interactions in diseases and aging and might ultimately lead to development of novel treatments.

  Complicit Organisations

1 Israeli organisation participates in SENESCENCE CLEARANCE.