Metabolism in Aging Processes, Diabetes and Obesity

Why is the sensation of hunger generated in the brain? Obesity and diabetes depend on neuronal signaling processes. Research Area F explores metabolic signaling pathways, those metabolic processes that regulate food intake and energy expenditure. These signaling pathways play a complex role in the genesis of aging-associated diseases. The TOR signaling network pass on metabolic signals. They play a key role in the development, growth, stress resistance, fertility, and aging process in human beings and so-called model organisms such as worms and flies.

Processes like insulin signaling cascades are crucial for regulating lifespan. Lower signal activity in this metabolic signaling network can increase longevity, improve function and health during aging, and protect from aging-associated diseases such as diabetes. In contrast, altered insulin signaling can also lead to obesity and type 2 diabetes mellitus (T2DM). Many molecules in the insulin/insulin-like growth factor/TOR signaling networks are potential drug targets. Indeed rapamycin, an effective and specific inhibitor of the kinase enzyme from the TOR network, prolongs the life of fruit flies and mice.

It is therefore essential to identify the exact changes in signalling, gene expression and physiology that promote health and minimise side effects. The central nervous system (CNS) plays a key role in the regulation of the peripheral metabolism. Determining these active mechanisms and identifying other peripheral tissue that further processes and conveys metabolic signals will lead to new drugs.

Here CECAD has derived research projects in three areas:

  1. System biology in the metabolic signaling processes
  2. Neuronal circuits and metabolic signaling processes
  3. New (non-standard) types of tissue as targets for metabolic signaling processes

CECAD’s research is highly socially relevant. Obesity is on the rise in Western cultures where around 30% of the population is affected. Excess fat and weight are directly linked to the genesis of insulin resistance and as such type 2 diabetes, diabetic complications and a range of skin problems, which come at a high cost to society.

Prof. Dr. Jens C. Brüning
CECAD Coordinator – Head of Research Area F, Principal Investigator – MPI for Metabolism Research
Tel.  +49 221 4726 202

Max-Planck-Institut für Stoffwechselforschung
Gleuler Str. 50
50931 Köln
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Jens C. Brüning

Prof. Dr. Linda Partridge
Head of Research Area F – Principal Investigator, Director of the Max Planck Institute for Biology of Ageing
Tel.  +40 (0) 221 4726 0

Max-Planck-Institut für Biolgie des Alterns
Gleueler Str. 50 A
50931 Köln
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Linda Partridge

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Figure 1: Important diagnostic: Magnetic Resonance Imaging

Figure 2: How does the reward circuitry work? What are the characteristic features of the nerve cells involved? Researchers at CECAD locate individual nerve cells and use techniques such as patch-clamp recordings to study their properties (shown here in the picture).

Figure 3: In the laboratory Drosophila melanogaster is kept in vials.

Figure 4: What is measured on an MRI? The human brain and its structure can be viewed under MRI. With the aid of a functional scanner, it is also possible to measure brain activity, e.g. in the reward center.

Figure 5: Focusing on neurons. Antibody staining of dopamine-secreting nerve cells of the midbrain – some of them are part of the limbic reward center (shown here in green).

Figure 6: A fruit fly (Drosophila melanogaster) on a grape (picture by courtesy of Sebastian Grönke).

Figure 7: Unraveling metabolism in aging, diabetes, obesity: The human brain plays a crucial role in metabolic signaling leading to aging-associated diseases.