Mitochondrial Dysfunction in Aging and Neurodegeneration

The CECAD Excellence Cluster has a vision: to understand the molecular basis of the aging process. To this end, scientists work to identify the processes implicated in triggering aging-associated diseases when they fail. The research projects in Research Area A are designed to explore the role of the mitochondria, the “powerhouses of the cell”, in these processes.

As the human body ages, mitochondrial dysfunctions increase and can lead to neurodegenerative diseases, especially in the brain. Aging correlates with an accumulation of mutations in mitochondrial DNA and a decline in the function of the respiratory chain that generates energy in the presence of the oxygen we breathe in. Whether a deterioration of mitochondrial activities is due to a downregulation of respiratory capacity or the accumulation of defects inside the mitochondria is still unclear.

This leads to a central issue CECAD research seeks to address: How can the quality of the mitochondria, their DNA, proteins and lipids be maintained throughout the entire lifecycle? The researchers’ work focuses on improving the understanding of the mechanisms that maintain the functional integrity of mitochondria with increasing age and protect us from neurodegeneration.

Strengthened by excellent scientific appointments in the first funding period, CECAD scientists in Research Area A are pursuing the following objectives:


  • The mechanisms that maintain mitochondrial genome integrity and its expression during aging
  • The mechanisms that regulate the production of energy via mitochondrial respiration during the aging process
  • The key components and signaling pathways that mediate increased longevity by regulating mitochondrial function
  • The mitochondrial quality control mechanisms that counteract an aging-association decline in mitochondrial activities
  • The mechanisms that underlie neurodegenerative disorders which are caused by a disruption of mitochondrial quality control

The CECAD scientists in Research Area A use a range of different model systems to explore these topics. Different mouse models are essential for researching neurodegenerative disorders triggered by mitochondrial dysfunction. These disorders include Parkinson’s disease, cerebellar ataxia (lack of muscle coordination caused by a dysfunction of the cerebellum), spastic paraplegia (increasing spasticity in the limbs), and a range of mitochondrial encephalopathies (a term that refers to pathological changes in the brain with a variety of causes and expressions). One important goal of this research is to improve our understanding of the processes that determine the activity and functionality of the mitochondria. These findings could then serve as a basis for developing new, long-term therapeutic approaches to counteract the aging process and the progression of aging-associated disorders.


Prof. Dr. Thomas Langer
Head of Research Area 1, Principal Investigator, Managing Director of MPI for Biology of Ageing
 +49 (0)221 379 70 502

Max-Planck-Institut für Biologie des Alterns
Joseph-Stelzmann-Str. 9b
50931 Köln


Prof. Dr. Elena I. Rugarli
Principal Investigator, Institute for Genetics
 +49 221 478 842 44

CECAD Forschungszentrum
Joseph-Stelzmann-Str. 26
50931 Köln


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Figure 1: Purkinje nerve cells link the granular to the molecular layer of the cerebellar cortex. This brain region controls balance and muscle coordination.

Figure 2: View of the network of nerve cells in the brain.

Figure 3 and 6: Absence of mitochondrial fusion leads to mitochondrial fragmentation and respiratory incompetence. Fzo1 is essential for the presence of tubular mitochondria. Mitochondrial morphology of (a) wild-type and (b) Δfzo1 yeast cells expressing a mitochondrial-targeted GFP protein. Cellular (Nomarsky) and mitochondrial (GFP) morphology were visualized by fluorescence microscopy.

Figure 4: An example of a model organism used for research: the threadworm C. elegans.

Figure 5: Mitochondria are dynamic parts of the cell.