by Gabriele Meseg-Rutzen, University of Cologne

Molecular consequences of mitochondria dysfunction in cartilage for skeletal aging processes. Credit: Science Advances (2025). DOI: 10.1126/sciadv.ads1842

An interdisciplinary research team led by Professor Dr. Bent Brachvogel has examined how mitochondria influence the premature aging of the skeleton. Mitochondria play a key role in the production of energy by way of cellular respiration. Researchers have discovered that a development-dependent, premature impairment of mitochondrial respiration is responsible for speeding up the process of skeletal aging.

The study was published under the title "Metabolic rewiring caused by mitochondrial dysfunction promotes mTORC1-dependent skeletal aging" in Science Advances.

The researchers undertook a specific in vivo analysis of the mitochondrial malfunction in the skeletal system using a mouse model. They were able to show that a development-dependent impairment of the mitochondrial cellular respiration in cartilage cells leads to long-term change in cell metabolism. As a result of this metabolic adaptation, the cells lose their ability to regenerate in the long term and die, so that aging processes in the skeleton are accelerated.

According to Professor Dr. Bent Brachvogel, the responsible last author of the study, "The fundamental processes identified here could establish the basis for new treatment strategies to influence cartilage degeneration and skeletal aging in the context of mitochondrial disorders at an early stage."

Skeletal aging processes are accelerated in mutant mice with a defective mtRC in chondrocytes. Credit: Science Advances (2025). DOI: 10.1126/sciadv.ads1842

The study was conducted in connection with the FOR2722 Research Unit. The research unit is examining the role of the extracellular matrix in the musculoskeletal system, the part of connective tissue that lies in the space between cells. The development of chronic degenerative diseases within the musculoskeletal system represents a particular area of focus here.

The study was led by the experimental neonatology team at University Hospital Cologne. Also participating in the study were researchers from the CECAD Cluster of Excellence for Aging Research, the Max Planck Institute for Biology of Aging and from the Faculties of Mathematics and Natural Sciences at the Universities of Cologne and Erlangen-Nürnberg.

More information: Kristina Bubb et al, Metabolic rewiring caused by mitochondrial dysfunction promotes mTORC1-dependent skeletal aging, Science Advances (2025). DOI: 10.1126/sciadv.ads1842  Journal information: Science Advances