Project description
How extracellular matrix composition influences ageing
In ageing, damaged senescent cells accumulate in organs, disrupting normal tissue function and contributing to ageing. It was recently found that damaged cells rely on integrins, critical cellular receptors that bind to the surrounding extracellular matrix (ECM). The ERC-funded ChECMate senescence project will investigate, for the first time, how the ECM composition and status can influence the accumulation of senescent cells by impacting the choice between senescence and cell death after injury. The project will study whether certain ECM proteins may promote abnormal senescence instead of cell death, examining multiple models to uncover the mechanisms controlling this phenomenon. It will establish a new approach to address ageing and tissue fibrosis.
Objective
The increasing elderly population poses a dual challenge to the viability of both global health and our current welfare systems. One of the pivotal aspects of aging involves the accumulation of damaged cells, known as senescent cells, in organs. While these cells play a role in coordinating tissue repair whenever damage occurs, their aberrant accumulation disturbs normal tissue function, resulting in an unbearable burden that ultimately leads to aging. Understanding how these cells accumulate within the organism, a yet unresolved question, would offer invaluable insights into the aging process. We have recently reported that damaged cells rely on Integrins, a family of membrane proteins, to implement senescence over cell death, leading to their accumulation within injured tissues. Remarkably, Integrins are known as the major cellular receptors binding to the surrounding extracellular matrix (ECM). Considering these precedents, we aim to take a step further and investigate whether the composition and status of the ECM can influence the buildup of senescent cells by impacting the choice between senescence and cell death upon injury, a possibility not explored before. Here, we aim to assess whether certain ECM proteins might act as pro-senescence factors by desensitizing damaged cells to death, favoring survival and aberrant senescence instead. We will thoroughly characterize multiple cell culture and mouse models of senescence implementation following damage, aiming to unveil the mechanisms controlling this phenomenon. Leveraging these findings, we will modulate the occurrence of cell senescence through ECM reengineering in mice, seeking to establish a revolutionary approach to address aging and tissue fibrosis. In sum, by uncovering unsuspected links between the ECM status and cell senescence implementation, ChECMate senescence would signify a paradigm change that would enable an unprecedented strategy in targeting cellular senescence in detrimental scenarios.
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.
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Programme(s)
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Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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HORIZON.1.1 - European Research Council (ERC)
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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.
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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.
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(opens in new window) ERC-2024-STG
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50009 Zaragoza
Spain
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