Project description
Understanding centromeres’ role in ageing genome instability
The occurrence of chronic diseases becomes common in the process of ageing, mainly due to genomic instability. In studies about telomeres and mutations, few have focused on centromeres which play an important role in the segregation of chromosomes. Recent studies indicate the occurrence of genome instability in immune cells because of centromere instability. The ERC-funded CenAGE project explores how ageing is influenced by instability in centromeres – key regions of chromosomes essential for correct cell division. It investigates how genetic, epigenetic and environmental factors, including viral infections, affect centromere function and contribute to inflammation, immune decline and cellular ageing. Using advanced genomic tools, it also tests whether targeting centromeres can slow ageing and improve health outcomes.
Objective
Ageing is the primary risk factor for chronic diseases. Amongst the ageing hallmarks, genomic instability has emerged as a unifying cause of ageing, since it drives most of the other hallmarks, namely senescence and chronic inflammation. These hallmarks are all typically portrayed by the aged immune system, with compelling evidence pointing to genomic instability in immune cells as a driver of organismal ageing. Intriguingly, while the role of telomeres, mutations, transposons, etc, in age-related genomic instability has been widely investigated, the centromeres have remained largely overlooked. Centromeres are unique specialised regions of repetitive sequences regulated epigenetically that ensure chromosome segregation fidelity. Emergent evidence shows that centromeres are inherently unstable, and recent findings from our labs indicate that centromere instability can lead to genome instability, inflammation, and senescence, including in non-cycling immune cells. In CenAGE, we propose a multi-layer synergistic approach to deliver a ‘centromeric’ view on ageing by: i) characterizing age-associated changes in centromere features in cellular models; ii) identifying the intrinsic (genetic and epigenetic) and extrinsic (viral infection) mechanisms behind centromere-driven senescence hallmarks; iii) establishing the role of centromere dysfunction in physiological decline, focusing on the immune system; and iv) testing how geroprotective interventions that implicate centromeres impact immunosenescence and systemic ageing. There is a timely opportunity to study centromeres in ageing now due to technological advances that enable the sequencing of these ‘blind spots’ of the genome. We expect the CenAGE project, grounded in solid preliminary results and complementary expertise, will deliver a transformative breakthrough in the field: centromeres as key players of genomic instability in ageing.
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 immunology
- natural sciences biological sciences genetics mutation
- natural sciences biological sciences genetics chromosomes
- natural sciences biological sciences genetics genomes
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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)
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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.
HORIZON-ERC-SYG - HORIZON ERC Synergy Grants
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Call for proposal
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(opens in new window) ERC-2025-SyG
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75654 Paris
France
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