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The Aging of Membranes

A key research question is why the lipid composition of the cell membrane changes with age. The aging process seems to alter the composition of lipids (fats), the building blocks of cell membranes. As a result, the structural properties of the cell membrane change as well. The lipid composition of membranes plays an important role in regulating the activity of cell surface membrane receptors, which transmit external signals to the cell interior and thereby control cell fate. In their search for definitive answers, scientists at CECAD combine mass spectrometry of membrane lipids with genetically defined deficiencies for specific enzymes involved in lipid metabolism to gain new insight into the characteristics of age-dependent changes of the lipid composition of cellular membranes and their impact on age-related diseases secondary to loss of cell function. By analysing the cellular lipidome, CECAD scientists have succeeded in improving our understanding of the changes of lipid composition occurring in aging membranes in mice and humans. The structural and functional characterization of aging membranes is an important component of CECAD’s ultimate goal: to identify the mechanisms that lead to aging.

Research Area D investigates the following research topics:

  • A precise understanding of the functional role of specific members of the ceramide synthase family that generate specific ceramide species (sphingolipids that are abundant building blocks of cellular membranes) in aging-associated disorders such as hair loss, muscle weakness or obesity.
  • Ceramide-specific control of mitochondrial functions in metabolic homeostasis.
  • Research into aging-associated changes in plasma membrane structure and inflammatory status caused by altered saturation and elongation of the polyunsaturated fatty acids (PUFA)
  • Effects of aging-associated changes in the lipids and the effect on mitochondrial membrane permeability and function, and ion channel function at the glomerular filter barrier in the kidney

CECAD expects these research activities will contribute considerably to the elucidation of triggers and progression factors driving aging-associated inflammation, neurodegenerative diseases, ceramide synthase-associated metabolic disorders, lipid-associated epidermal barrier function, mitochondrial-linked neurodegenerative diseases, and kidney failure.

Prof. Dr. Martin Krönke
Head of Research Area D – Principal Investigator, Institute for Medical Microbiology, Immunology and Hygiene (IMMIH)
Tel.  +49 221 478 32000
m.kroenke[at]uni-koeln.de

Institut für medizinische Mikrobiologie, Immunologie und Hygiene
Uniklinik Köln
Goldenfelsstr. 19-21
50935 Köln
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Martin Krönke
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Figures
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
 

Figure 1: Lipid bilayer of cellular membranes

Figure 2: ER association of GFP-tagged Ceramide synthase 1 in COS cells (super resolution microscopy, stimulated emission depletion (STED))

Figure 3: Building blocks of the lipid bilayer

Figure 4 AND 5: Enzymatic activity and tissue specific expression of ceramide synthases 1–6