Project description
Mitochondrial DNA and cell senescence
Cellular senescence is a stress response that involves irreversible proliferative arrest and the expression of inflammatory factors known as the senescence-associated secretory phenotype (SASP). While senescence acts as a tumour-suppressing mechanism by limiting the proliferation of potentially cancerous cells, the accumulation of senescent cells in ageing and disease can lead to harmful effects, particularly due to the SASP. With the support of the Marie Skłodowska-Curie Actions programme, the MitoDNASen project aims to explore the role of mitochondrial DNA (mtDNA) maintenance in SASP expression, as alterations in mtDNA and its replication have been linked to senescence. Preliminary results suggest that increased mtDNA copy number promotes SASP expression. The goal is to identify potential targets to modulate SASP and mitigate the negative impact of senescent cells.
Objective
In response to various stresses such as DNA damage, telomere erosion, or oncogene activation, human cells can enter senescence. This process is characterized by irreversible proliferative arrest, deep transcriptional reprogramming, and expression of a collection of inflammatory factors termed the SASP (senescence-associated secretory phenotype). As it limits the proliferation of cells potentially bearing neoplastic potential, the triggering of cellular senescence is an essential tumor suppressing mechanism. However, the persistence and accumulation of senescent cells in aging and pathological contexts can have deleterious effects, particularly due to the SASP. It is thus fundamental to understand the basic physiology of senescent cells to develop so-called senomorphic drugs that modulate SASP expression. Changes in mitochondrial physiology elicited during cellular senescence onset strongly suggest that the maintenance and integrity of their mitochondrial DNA (mtDNA) may be altered. For instance, cytosolic leakage of mtDNA has been shown to take place in senescent cells and participate in SASP expression via immune pathways activation, but the contribution of mtDNA metabolism and replication in SASP expression has not yet been explored. My preliminary results show that mtDNA copy number increases continuously during senescence progression, accompanied by recomposing of the mitochondrial replisome. I also showed that this increase in mtDNA copy number promotes SASP expression. In the present project, I will characterize in details the alterations in mtDNA maintenance and integrity during senescence; profile the evolution of mitochondrial replisome composition; and characterize how the previous regulate SASP expression. The perspective of this project is to identify new senomorphic targets for controlling SASP expression and hereby alleviate the adverse effects of senescent cells in pathological contexts.
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.
- natural sciences biological sciences genetics DNA
- natural sciences biological sciences cell biology cell metabolism
- medical and health sciences basic medicine immunology
- medical and health sciences basic medicine physiology
You need to log in or register to use this function
We are sorry... an unexpected error occurred during execution.
You need to be authenticated. Your session might have expired.
Thank you for your feedback. You will soon receive an email to confirm the submission. If you have selected to be notified about the reporting status, you will also be contacted when the reporting status will change.
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.
-
HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA)
MAIN PROGRAMME
See all projects funded under this programme
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.
HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships
See all projects funded under this funding scheme
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) HORIZON-MSCA-2023-PF-01
See all projects funded under this callCoordinator
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.
901 87 UMEA
Sweden
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.