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Dr. Thomas G. Hofmann

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Head of the junior research group "cellular senescence" at the German Cancer Research Center in Heidelberg

 

Hofmann; Foto von Michael Doh, NAR

Interview of March 19, 2009 with Dr. Birgit Teichmann

 

You are the head of the junior research group “cellular senescence”.  How do you explain cellular senescence?

Cellular senescence is a genetically controlled program, which limits the life span of cells. As a rule, normal cells divide 40-50 times and then the potential to divide is exhausted and cells fall into sort of a retirement, called cellular senescence, also known as aging of the cells.

 

 

 

 

What activates the senescence program?

There are a number of causes. In the meantime there is consensus that stress signals may be the main cause. If you think about aging of the skin for instance, increased UV exposure, e.g. through excessive sun bathing, promotes aging of the skin because UV-light damages the DNA. These DNA damages are accumulative in the cells and eventually it calls for the apoptosis or senescence program: the cells are killed or frozen in the cell cycle. The ability of the skin to regenerate decreases faster and the skin ages prematurely.

 

 

 

What connection is there between senescence and cancer?

Cancer cells have the ability to get around the senescence program. It is interesting that the senescence program is also a protective mechanism, which keeps damaged cells from passing on their genetic information by inhibiting division. Cancer cells avoid the program by potentially becoming immortal, meaning they are able to continuously divide and pass on their cancer promoting genetic defects to the daughter cell.

 

 

 

Why do we age? Do all cells age equally fast?

Aging of the organism is naturally much more complex than the aging process on a cellular level, as we view it in my working group. Many factors play a role. What we know in the meantime is that cells in the organism show certain markers for cellular senescence. This points to the fact that aged and functionally disturbed cells can be found more often in an aging organism. The cause of this may be that the regeneration potential that is necessary to keep our body fit and to replace old cells in tissues is simply eventually depleted. This may have several reasons: The stem cell reservoir ages or the stem cells die of apoptosis and there is no more supply of new cells. Cells in tissue are no longer replaced which leads to aging, respectively to the aging phenomenon. 

 

 

 

The C. elegans or the mouse is often used as a model organism for cell aging. Why not the turtle for instance, which really ages?

Aside from the fact that it would be interesting to keep a turtle in the laboratory, the reason for the C. elegans  is that the worm has a short life span and is easily genetically manipulated as a model organism, for instance, to test for a higher life span. One can perform complete genomic screenings in these worms and therefore identify new genes for longevity.

The mouse is already more complex, but has the advantage that it is a mammal and the result is transferable to higher organism, such as the human. It is a model system, much closer to the human than the round worm. On the other hand, genetic manipulations on the mouse are much more complex and difficult.

 

 

 

How does the citizen benefit from your research results?

Our goal is to understand how cancer cells are able to by-pass the cellular senescence program to become potentially immortal. We want to identify new components, building blocks which are important to call up the senescence and apoptosis program. Finally we want to test how they have changed in tumours. By reconstructing these building blocks, tumours may be disarmed and forced into cell aging and cell death stopping the tumour growth.

 

 

 

What advantage do you expect by integrating into the Network Aging Research, in which scientists of many research areas work together?

Based on the fact, that cell aging and also organic aging is a very complex process, it is very profitable to examine this question within a network in which aging is looked at from all aspects and as a whole, which could not be covered by laboratory work. Because of the Network the aging process can be viewed from different standpoints, which is positive for each particular project and it enables us to look and test for new cross links, which we could not attempt as a single institution.

 

 

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Latest Revision: 2018-06-13