Project description
The impact of ageing on stem cell regenerative potential
Tissue regeneration is facilitated by quiescent resident stem cells that become activated upon injury or the need to replace tissue-specific cells. Accumulating evidence indicates that with ageing, muscle stem cells known as satellite cells (SCs) lose their regenerative capacity, decrease autophagy and reprogram their circadian transcriptome. With this in mind, scientists of the EU-funded CIRCautophAGING project will investigate the mechanisms required to preserve stem cell regenerative fitness throughout life. They are working under the hypothesis that SC fitness is driven by an interplay between active autophagy and circadian regulation. Using transgenic animals, they will provide fundamental knowledge on stem cell biology and ageing, opening new avenues for regenerative therapies.
Objective
Regeneration of skeletal muscle relies on its stem cells, also called satellite cells (SCs). These cells remain quiescent throughout their life, and only activate in response to injury to form new muscle fibers. The regenerative capacity of these cells declines with aging. In the past years, Pura Muñoz Cánoves’ lab showed that, with aging, quiescent SCs 1) lose basal autophagy and 2) reprogram their circadian transcriptome (including the autophagic transcriptome). The molecular bases of these processes, their potential interrelation and the consequences of their failure with aging, are unknown. Our integrating hypothesis is that active autophagy and circadian regulation are interconnected and required to preserve stem cell regenerative fitness throughout life. We aim to answer the following questions: Which is the relative contribution of the stem-cell-intrinsic versus the organismal clock to muscle regeneration during aging? Are circadian and autophagy processes interconnected? This is, does circadian clock disruption alter autophagy in SCs? Conversely, does autophagy disruption affect their circadian regulation? If so, does autophagy re-induction by nutritional regimes restore circadian and regenerative functions in aged SCs? Mice genetically-modified for depletion of 1) selected circadian clocks or 2) autophagy will allow us to assess the relative contribution and interrelation of autophagic and circadian machineries to muscle regeneration during aging. We expect that completion of this project will provide new fundamental knowledge on stem cell biology, regeneration and aging, which will open opportunities for stem cell rejuvenation.
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.
- engineering and technology mechanical engineering vehicle engineering aerospace engineering satellite technology
- natural sciences biological sciences cell biology
- medical and health sciences medical biotechnology cells technologies stem cells
- natural sciences biological sciences genetics RNA transcriptomes
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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-2019
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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.
08002 Barcelona
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.