Molecular mechanisms in ageing and age-associated diseases

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 aging population poses a double challenge. The first challenge involves investigating fundamental aging 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 join forces to conduct interdisciplinary research into these issues, with the ultimate objective of facilitating “healthy aging”.

Molecular mechanisms in ageing

Ageing is an elementary part of life, and yet many of the physiological processes associated with it are still not understood. Ageing research, successfully established as a key area at Ulm University’s Faculty of Medicine, should remedy this situation. Research focuses not only on the molecular mechanisms in degenerative aging processes, but also on the emergence of ‘age-related’ diseases, which occur more frequently in old age. In the long term, the objective is to develop preventive and therapeutic strategies which will enable people to achieve ‘healthy ageing’. In addition to exploring primary ageing processes that occur in the organism – without external stimulus – scientists are also investigating secondary ageing processes caused by the effects of environmental factors.

Old and young stemm cells
Old and young stemm cells

A wide range of research issues is being explored

Here are just a few examples:

  • How do connective tissue cells protect themselves from oxidative stress?
  • Which signalling pathways promote ageing processes, and which inhibit them?
  • How do repair enzymes protect DNA from damage resulting from ageing?
  • What influence do telomeres – i.e. the ends of chromosomes – have on cell division rates and lifespans?

From apoptosis research to stem cell therapy

Put simply, 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 at Ulm are now studying how to retain the repair potential of stem cells by rejuvenating them. Apoptosis research follows a completely different approach. In this strain of research, scientists are exploring the determinants and consequences of “programmed” cell death. After all, this cellular “suicide programme” protects regeneration processes against uncontrolled growth effects, helping to prevent the development of tumours, for example.

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 at 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 help us understand better the genetic and molecular causes of age-related degenerative processes. The SyStaR consortium, funded within the BMBF (German Federal Ministry of Education and Research) programme GerontoSys, is an alliance comprising Ulm hospitals, basic researchers, bioinformaticians and mathematicians. Together, they are pursuing two central research objectives.

Research focuses on identifying the molecular mechanisms that contribute to preserving stem cell function and retaining 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 makeup and personal lifestyle, varies accordingly from individual to individual.

Working with UV at the Institute of Experimental Cancer Research.
Working with UV at the Institute of Experimental Cancer Research.

Age-related diseases

Age is a significant risk factor for human health. That is, whereas ageing per se is not viewed as an illness, certain diseases occur more frequently with age. These age-related diseases are a result of the increased susceptibility to damage of the organism, which loses its adaptability and resilience over time. An additional objective of ageing research is, then, not only to extend the life span by supporting prevention and treatment, but also to ideally enable people to achieve "healthy ageing".

Typical age-related diseases are cardiovascular diseases; musculoskeletal disorders such as osteoporosis and arthrosis; and lipid and glucose metabolism disorders (obesity and type II diabetes mellitus). Added to these are neurodegenerative diseases such as Alzheimer’s and, of course, cancer.

 

 

At Ulm University, medical experts join forces with natural scientists to conduct research in numerous interdisciplinary projects on the causes of a variety of age-related diseases. The objective is to transfer basic knowledge to clinical practice. In addition, other scientists are exploring the progressive loss of body functions per se. This entails, for example, age-related alterations of the immune system or connective tissue, which are associated with wound healing disorders.

The research training programme Cellular and Molecular Mechanisms in Ageing

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. By establishing a research training programme on Cellular and Molecular Mechanisms in Ageing (CEMMA), Ulm University has a tailor-made training programme 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 Cellular and Molecular Mechanisms in Ageing (CEMMA) is part of the International Graduate School in Molecular Medicine Ulm (IGradU). It is funded by the Deutsche Forschungsgemeinschaft (German Research Foundation, DFG) within the framework of the Excellence Initiative.

Investigation of molecular and cellular mechanisms of ageing processes in the lab.
Investigation of molecular and cellular mechanisms of ageing processes in the lab.