Molecular mechanisms in ageing and age-related diseases: How can we age healthily?

Despite being tempted by the idea of eternal youth, to many, the thought of becoming frail in old age is frightening. For the life sciences, the ageing population poses a double challenge. The first challenge involves investigating fundamental ageing processes at the molecular biological level. The second challenge faced by researchers involves searching for effective therapies or methods of preventing age-related diseases such as diabetes, osteoporosis, arthritis and, not least, cancer.
Scientists at Ulm University have joined forces to conduct interdisciplinary research into these issues, with the ultimate objective of facilitating 'healthy ageing'. The expertise of basic science researchers and clinically oriented scientists is bundled at the aging research center (arc uulm). This translational approach is a special strength of Ulm's ageing research.

Deutsche Forschungsgemeinschaft (DFG)
Federal Ministry of Education and Research (BMBF)
European Union (incl. ERC Advanced Grants)
state funds, private trusts et al.
Endowed Professorship for Neurodegeneration (Charcot Foundation)
Endowed Professorship for Neuroanatomy of Vascular Diseases (Corona Foundation)
DFG Heisenberg professorship integrative genomic and epigenomic analyses of acute myeloid leukaemia

Networking in Ulm
Cooperation with various departments of the University Hospital
aging research center (arc uulm)
CEMMA Research Training group in aging

International Graduate School in Molecular Medicine Ulm (IGradU)
Comprehensive Cancer Center Ulm (CCCU)
Boehringer Ingelheim Ulm University BioCenter (BIU)
Else Kröner research training group on stem cells, ageing and malignant transformation
Agaplesion Bethesda Clinik Ulm (geriatric hospital)

Topics et all.
Cross-section aging of cells, stem cells and organs
Development of novel therapies
Haematology and Oncology

Prof. Dr. Hartmut Geiger, Institute of Moleculare Medicine

Participating institutes and clinics

Institute for Molecular Medicine
Prof. Dr. Hartmut Geiger
Institute of Anatomy and Cell Biology
Prof. Dr. Tobias Böckers, Prof. Dr. Nikola Golenhofen
Institute of Molecular Virology
Prof. Dr. Frank Kirchhoff, Prof. Dr. Jan Münch
Institute of Physiological Chemistry
Prof. Dr. Thomas Wirth, Prof. Dr. Bernd Knöll
Institute for Clinical Transfusion Medicine and Immunogenetics
Prof. Dr. Hubert Schrezenmeier
Institute of Human Genetics
Prof. Dr. Reiner Siebert, Prof. Dr. Guntram Borck, Prof. Dr. Ole Ammerpohl
Institute of Applied Physiology
Prof. Dr. Birgit Liss, Prof. Dr. S. Grissmer
Institute of Pharmacology and Toxicology
Prof. Dr. Peter Gierschik, Prof. Dr. Holger Barth, Prof. Dr. Oliver Zolk
Institute of Pathology
Prof. Dr. Peter Möller
Institute of Immunology
Prof. Dr. Hassan Jumaa
Institute for Experimental Tumor Research
Prof. Dr. Christian Buske
Institute of Anaesthesiological Pathophysiology and Process Development
Prof. Dr. Dr. h.c. Peter Radermacher
Institute of Biochemistry and Molecular Biology
Prof. Dr. Michael Kühl, Prof. Dr. Gilbert Weidinger
Institut of Medical Systems Biology
Prof. Dr. Hans Kestler
Institute of Epidemiology and Medical Biometry
Prof. Dr. Dietrich Rothenbacher
Clinik for Dermatology and Allergology
Prof. Dr. Karin Scharffetter-Kochanek
Clinic for Neurology
Prof. Dr. Albert Ludolph
Internal Medicine Clinic III
Prof. Dr. Hartmut Döhner
Gynaecological Clinic
Prof. Dr. Lisa Wiesmüller
Department of Paediatrics and Adolescent Medicine
Prof. Dr. Klaus-Michael Debatin
Prof. Dr. Pamela Fischer-Poszovsky
Internal Medicine Clinic I
Prof. Dr. Thomas Seufferlein

Molecular mechanisms in ageing

Ageing is an elementary part of life, and yet many of the physiological processes associated with it are still poorly understood. Ageing research, successfully established as a key area at Ulm University’s Faculty of Medicine, strives to remedy this situation. Investigations focus both on the molecular mechanisms in degenerative ageing processes as well as on the emergence of ‘age-related’ diseases, which are more prevalent in the older population. In the long term, the objective is to develop preventive and therapeutic strategies which will enable people to achieve a state of ‘healthy ageing’. In addition to exploring primary ageing processes that occur in the organism – without external stimulus – scientists are also exploring secondary ageing processes caused by the effects of environmental factors.

Important research questions in this context are:

  • How do connective tissue cells protect themselves from oxidative stresss?
  • Which signalling pathways promote ageing proceses, and which inhibit them?
  • How do repair enzymes protect DNA from ageing-related damage?
  • How does the ageing of stem cells influence the ageing of different tissues?
  • Can the ageing of cells be reversed?

Regeneration and stem cell therapy

Simply put, ageing involves a complex interplay between regeneration and degeneration. For this reason, stem cells play a key role in ageing. Thanks to their regenerative potential, stem cells can partially compensate for or, ideally, repair injured tissue and organs. But the older stem cells are, the weaker their 'healing' powers become. Scientists in Ulm want to retain the repair potential of stem cells by rejuvenating them. The reversibility of the ageing process of haematopoietic bone marrow stem cells has already been proven by the researchers around Professor Hartmut Geiger, Director of Ulm's Institute of Molecular Medicine.

Old and young stem cells

Systems biology approaches in ageing research

Both the regeneration and degeneration of cells, tissues and organs are controlled by genetically determined molecular mechanisms. A whole array of longevity genes have already been identified. At the same time, scientists are also aware of numerous factors that accelerate ageing processes or that trigger age-related diseases such as cancer. This knowledge also comes into play in ageing research in Ulm; not least using systems biology approaches, which combine knowledge generated from the lab with mathematical concepts, enabling computer-based processing.

Ultimately, the reason for combining experimental data with computer models is to advance the understanding of the genetic and molecular causes of age-related degenerative processes. The SyStaR consortium is an alliance comprising physicians, basic researchers, bioinformaticians and mathematicians in Ulm and receives funding through the BMBF (Federal Ministry of Education and Research) programme GerontoSys. Together, these experts are striving to identify the molecular mechanisms that contribute to the preservation of stem cell function and the regenerative capacity of organs. A second strain of research involves developing biomarkers to establish the ‘true biological age’ of an individual. This figure, which depends on individual factors such as a person’s genetic make-up and personal lifestyle, varies accordingly from person to person. However, more and more interconnections are being discovered between the previously distinctly separate theories on ageing.

Age-related diseases

Ageing is a significant risk factor for personal health. Although ageing itself should not be regarded as a disease of course, incidences of certain ailments are more common in older people. These illnesses are the result of the organism's heightened susceptibility to damage as it loses its capacity for adaptation and resistance. Another research objective is therefore to go beyond the mere expansion of the lifespan through prevention and therapy of age-related diseases and enable humanity to "age healthily".

Typical age-related diseases are the classic neurodegenerative illnesses such as Alzheimer’s and Parkinson's disease, but also cardiovascular diseases as well as musculoskeletal disorders such as osteoporosis and arthrosis. Added to these are lipid and glucose metabolism disorders (obesity and type II diabetes mellitus) and cancer.

At Ulm University, physicians and natural scientists research together in numerous interdisciplinary projects on the causes of these diverse "old-age diseases". Their goal is to transfer basic scientific findings into clinical application. Other groups also investigate the progressive loss of body functions itself. One of their main interests are age-related changes in the immune system or the connective tissue, which are accompanied by impaired wound healing.

Apoptosis research uses a completely different approach; this speciality explores the prerequisites and consequences of "programmed" cell death, as this cellular "suicide programme" protects regenerative processes from uncontrolled growth effects and thus helps prevent the development of tumours, among other things.

The research training programme on ageing – CEMMA

The more the population ages, the more pressing it becomes to fully understand ageing processes and age-related diseases. Not least, it is essential to make sure that young scholars are equipped to meet these challenges. In addition to the opportunities provided within the Emmy Noether Programme, Ulm University has established a research training programme on Cellular and Molecular Mechanisms in Ageing (CEMMA) to familiarise young physicians and natural scientists with the key issues concerning ageing research.
Investigations focus on the molecular and cellular mechanisms of ageing processes, and the resulting potential for new therapeutic approaches. The research training programme CEMMA is part of the International Graduate School in Molecular Medicine Ulm (IGradU) (Link). It is funded by the German Research Foundation (DFG) within the framework of the Excellence Initiative. At the end of 2017, the research training programme was granted an extension of another four and a half years.


Watch Prof. Hartmut Geiger at TEDx Talks in Linz: Engineering healthy aging, one stem cell at a time