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Content archived on 2024-06-18

Generation of mouse models for the study of cellular senescence in aging and cancer

Objective

Cellular senescence is a central biological mechanism for cancer prevention in mammals. Cells enter senescence when tumor-inducing genes are aberrantly activated, and in response undergo an arrest in proliferation accompanied by dramatic changes in metabolism and morphology, thus preventing their further development into tumors. Various types of physiologic stresses can also induce senescence, and this process is thought to play a central role in promoting aging, possibly by limiting the proliferative potential of stem-cell pools. While much is known about senescence in cultured cells, basic questions regarding the roles of this process in the living organism are still unanswered. In this proposal we describe the development of systems for the study of senescence in the living organism. We utilize the two central molecular activators of senescence: the p16INK4a and p19ARF genes. These genes are specifically induced during cellular senescence, and their expression is sufficient to induce this state. We will develop and characterize mice in which the expression of p16INK4a or p19ARF can be induced in multiple tissues through tetracycline administration, in order to induce cellular senescence in these tissues. This will allow us to experimentally generate senescent cells in the adult mouse and characterize their molecular and functional traits. We will study the effects of cellular senescence on tissue and organism physiology, and assess whether induction of senescence induces aging-like phenotypes. This system will provide the first genetic system to study this central biological program in its proper physiologic context, shedding light on aging processes and cancer prevention mechanisms.

Fields of science (EuroSciVoc)

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Keywords

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Topic(s)

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Call for proposal

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FP7-PEOPLE-2007-4-3-IRG
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Funding Scheme

Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.

MC-IRG - International Re-integration Grants (IRG)

Coordinator

THE HEBREW UNIVERSITY OF JERUSALEM
EU contribution
€ 100 000,00
Address
EDMOND J SAFRA CAMPUS GIVAT RAM
91904 JERUSALEM
Israel

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Activity type
Higher or Secondary Education Establishments
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

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