Mitochondrial dysfunction in ageing and new therapies
Description: Mitochondrial DNA (mtDNA) depletion and deletions are linked to severe genetic disorders and age-related diseases, yet their causal role remains unclear. In this project, we investigate both the mechanistic causes of these mtDNA changes and whether restoring mtDNA homeostasis can mitigate disease phenotypes. Our recent work, now advancing to clinical trials, has led to the development of small-molecule activators that enhance mutant mitochondrial DNA polymerase gamma (POLγ) function, restoring mtDNA levels. We will extend these findings by exploring pharmacological strategies to modulate nucleotide availability and prevent mtDNA instability. Using advanced sequencing, biochemical, and disease modeling approaches, we will define how mtDNA alterations drive pathology in mitochondrial and common age-related disorders, including inclusion body myositis. This project is embedded within the Center for Advanced Mitochondrial Studies (CAMS), fostering collaborations between fundamental and clinical researchers to accelerate the development of mitochondria-targeted therapies.
Funder: Vetenskapsrådet
Amount: SEK 30,800,000
Funding type: research
Funder scheme: Research environment
Start date: 2026-01-01
End date: 2033-12-31
Investigator: Claes Gustafsson
Institution: University of Gothenburg
Funded outputs count: 1
Funder award ID: 2025-01111
OpenAlex ID: G3537955675