An interdisciplinary research team led by Professor Dr. Bent Brachvogel has studied how mitochondrial malfunctions contribute to premature skeletal aging.

Disorders affecting mitochondrial function are linked to skeletal issues like stunted growth and premature cartilage degeneration, but the underlying molecular mechanisms were previously unclear.

A study from the University of Cologne reveals that mitochondrial dysfunction can trigger early-onset skeletal aging by disrupting cartilage metabolism.

The study utilized a genetically modified mouse model with a mutation in the Twinkle gene, impairing mitochondrial DNA replication and respiratory chain function.

This research demonstrated long-term metabolic changes in cartilage cells due to mitochondrial dysfunction.

The research focused on growth plate cartilage, which shifts from glycolysis to oxidative phosphorylation after birth; disruptions in this shift can accelerate skeletal aging.

Impaired cartilage cells lose their regenerative capabilities and eventually die, leading to accelerated aging processes in the skeleton.

This metabolic adaptation initially helps cells cope with stress but eventually causes overactivation of the mTORC1 signaling pathway, disrupting essential cellular processes.

The activation of mTORC1 was linked to abnormal accumulation of matrix proteins and signs of premature aging in cartilage cells.

The findings suggest that targeting mitochondrial metabolism and modulating mTORC1 activity could lead to new treatments for cartilage degeneration and age-related skeletal conditions.

Supplementation with nicotinamide mononucleotide (NMN) helped restore redox balance and improve cell survival, indicating potential therapeutic avenues.

Further research is needed to confirm these mechanisms in human cartilage and to assess the long-term effects of potential interventions.