Skip to main content
Go to the home page of the European Commission (opens in new window)
English en
CORDIS - EU research results
CORDIS

Deciphering the interplay between mitophagy, epigenetic regulation, and neurodegeneration in ageing

Project description

Cracking the code of brain ageing

As we get older, our brain starts to accumulate damaged mitochondria. It undergoes subtle changes in gene regulation, which can contribute to neurodegeneration. Mitophagy, the natural process that clears faulty mitochondria, starts to slow with age. This is why boosting it has shown promise for protecting neurons. Supported by the Marie Skłodowska-Curie Actions programme, the MitoEpigeNeAge project will use the model organism Caenorhabditis elegans (C. elegans), along with optogenetics and super-resolution imaging, to uncover how mitophagy influences redox-regulated epigenetic changes in ageing neurons. By identifying molecular links between mitochondrial quality control and gene regulation, the project could open new paths to tackling age-related neurodegenerative diseases.

Objective

"The ""MitoEpigeNeAge"" research proposal seeks to uncover the molecular mechanisms of age-related neurodegeneration by focusing on the interplay between mitophagy, redox-regulated histone methylation, and neuronal death. Brain ageing is characterized by the accumulation of damaged mitochondria and epigenetic changes, leading to neurodegeneration. Mitophagy, the process that clears damaged mitochondria, declines with age but extends lifespan and offers neuroprotection when activated. However, its impact on the epigenome remains unclear. The project will utilize Caenorhabditis elegans due to its well-defined nervous system and evolutionary conservation of neuronal ageing mechanisms. Advanced technologies will analyse chromatin accessibility and gene expression in redox-sensitive neurons. Super-resolution imaging and optogenetics will allow precise manipulation of mitochondrial damage and mitophagy in live animals. Key objectives include: 1) Monitoring chromatin accessibility, histone methylation, and gene expression in wild-type and mitophagy-deficient worms; 2) Developing in vivo reporters to track chromatin modifications during ageing and mitophagy induction; 3) Using optogenetics to assess the effects of mitochondrial damage on histone methylation in neurons; 4) Exploring if mitophagy-inducing interventions provide neuroprotection through changes in histone methylation linked to redox homeostasis; 5) Conducting a genetic screen to find mitophagy modulators that enhance mitochondrial quality control, histone methylation, and resistance to neurodegeneration. This project supports the researcher’s long-term goals and the MSCA's mission to promote innovative research. Its successful completion will greatly enhance understanding of age-related neuronal decline, with significant benefits for human health. The MSCA grant would be transformative, providing essential resources to advance the research and establish the researcher as a group leader in the ageing field."

Fields of science (EuroSciVoc)

Keywords

Programme(s)

Topic(s)

Funding Scheme

HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships

See all projects funded under this funding scheme

Call for proposal

(opens in new window) HORIZON-MSCA-2024-PF-01

See all projects funded under this call

Coordinator

ETHNIKO KAI KAPODISTRIAKO PANEPISTIMIO ATHINON
Net EU contribution
€ 181 423,68
Address
6 CHRISTOU LADA STR
105 61 ATHINA
Greece
Region
Αττική Aττική Κεντρικός Τομέας Αθηνών
Activity type
Higher or Secondary Education Establishments
Links
Total cost
No data