Objective
Research over the last decade has convincingly evidenced that cellular senescence and low oxygen (O2) availability (hypoxia) are distinctive features involved in the physiopathology of age-related disorders including lung cancer and Alzheimer’s disease (AD). Cellular senescence is characterised by a permanent and irreversible cell cycle arrest and the acquisition of an intense senescence associated secretory phenotype (SASP). Mounting evidence has shown that the SASP accounts for most of the detrimental effects of senescent cells accumulated in aged tissues. Therefore, understanding the mechanisms that modulate the composition and intensity of the SASP is a fundamental biological question with significant translational implications in age-related disorders.
Senescent cells accumulate in tissues where O2 is very limited. To live under these conditions, senescent cells must adapt to hypoxia via the stabilisation of hypoxia inducible transcription factor (HIF). I hypothesise that local hypoxia determines the composition and intensity of the SASP in age-related disorders, a concept that I will name hSASP. Given the intrinsic heterogeneity of the SASP across tissues, I will test this hypothesis in lung cancer and AD models where there is a concomitant accumulation of senescent cells in hypoxic areas. I will use a variety of genotoxic agents to induce cellular senescence in lung cancer and stromal cells as well as in murine primary astrocytes exposed to a decreasing range of O2 tensions. I will elucidate the role of hypoxia in regulating the composition and intensity of the hSASP and its paracrine effects on nearby cells. Finally, I will identify relevant hSASP factors and define their functional effects on lung cancer and microglial cells.
Targeting specific hSASP factors may offer new therapeutic opportunities to attenuate the adverse effects of senescent cells accumulated in age-related disorders such as lung cancer or AD.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- medical and health sciences basic medicine neurology dementia alzheimer
- medical and health sciences clinical medicine oncology lung cancer
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Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions
MAIN PROGRAMME
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H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility
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Topic(s)
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
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.
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.
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)
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Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) H2020-MSCA-IF-2020
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Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.
41013 Sevilla
Spain
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.