Brachvogel, Bent - C 03

Progressive decline in mitochondrial respiratory chain (mtRC) activity is a hallmark of aging, linked to metabolic adaptation responses. Patients with impaired mtRC function often exhibit early growth retardation as a sign of accelerated aging, but the mechanisms by which metabolic reprogramming contributes to this process is unclear. Our recent work showed that an initially beneficial activation of the reductive TCA cycle in transgenic mice with mtRC dysfunction ultimately triggers premature growth retardation driven by mTORC1 hyperactivation, impaired extracellular matrix formation and increased cell death (Bubb et al. Sci Adv. 2025). This cell death-driven tissue degradation occurs too early relative to chronological age and is considered a sign of accelerated aging. Notably, correcting reductive imbalance restores cell survival, highlighting redox imbalance as a key metabolic target in cells with mtRC dysfunction. The primary focus of this project is to investigate the mechanisms by which reductive insults accelerates age-related tissue degeneration, particularly in a human context, using a human organoid 'in-a-dish' system. 

Our overarching goal is to precisely define the underlying mechanisms and assess the translational potential of these approaches.

Reductive imbalance is a key therapeutic target in age-related mitochondrial diseases, yet how their correction leads to improved outcomes is not known. This project aims to uncover how redox imbalance drive aging processes and will provide crucial fundamental insights for targeting reductive insults in this process, with broader implications for related conditions such as metabolic syndrome, cardiovascular disorders, and neurodegenerative diseases.

Human induced pluripotent stem cell–derived organoid cultures are employed to dissect the mechanistic consequences of reductive imbalance in aging processes and to develop targeted therapeutic approaches. 

• Center for Molecular Medicine Cologne (CMMC)
• Experimental Neonatology (UHC)
• CECAD Research Center
• FOR 2722

For more information, please check the research page of Prof Brachvogel.