Ageing is a complex biological process characterized by the organism’s failing ability to maintain one or more biochemical
functions. Therefore ageing often leads to an increase of various different age-related diseases including cancer, dementia,
cardiac and vascular diseases plus other conditions which lead to a fast weakening of the individual.
The Danish Centre for Molecular Gerontology (DCMG) was established in 1996. At the end of 2001 a
grant from the Danish Government for continuation of part of the Centre has enabled further scientific research
to be undertaken within the network aiming at obtaining results in the field of molecular biology and genetics. The centre is now embedded at the Faculty of Science at Aarhus University, Denmark.
The overall goal of DCMG is to understand the basic molecular biological mechanisms that result in a progressive impairment
of functional ability, which leads to the occurrence of several age-related diseases. Since the incidence of various
disorders, including cancer, cardiovascular disease, diabetes and osteoporosis increases dramatically with age, it
is crucial to understand why and how old individuals become prone to these diseases, and what effective means of
intervention and prevention can be developed.
Age-associated diseases are very costly to the society, both in terms of finances and in terms of the loss of quality of life.
Main foci of research and collaborations in DCMG:
- The role of DNA damage in ageing and age-associated disease
It has been shown that during ageing, there is a steady accumulation of damage to the genetic material, DNA. We are investigating the underlying causes of this, which may be related to a defective DNA repair processes. We are also studying the consequences of the DNA damage, which might be related to the high degree of genomic instability seen with ageing. Furthermore, our research focuses on the mechanisms of DNA damage processing and the role of specific enzymes in this process.
- Human ageing and premature ageing syndromes
We are carrying out molecular and biochemical studies of cells and purified proteins from patients with the so-called premature ageing syndromes. These include Werner’s syndrome, Cockayne syndrome, Xeroderma Pigmentosum and Hutchinson Guilford syndrome. These human diseases are characterized by a phenotype or appearance where the individuals appear much older than their chronological age. In addition, we also investigate underlying causes of Alzheimer’s and Parkinson’s disease.
- Telomeric-regulation of cellular ageing
A hallmark of cellular ageing is the Hayflick phenomenon that reflects that normal, diploid and differentiated cells only undergo a limited number of doublings before they senesce. One of the mechanisms of replicative senescence is the progressive loss of chromosomal ends known as telomeres. We are exploring this process at various levels in order to find a potential relationship between ageing, age-related diseases, lifespan and chromososme-specific telomeric alterations.
- Changes in gene expression and function with ageing
An important aspect of the ageing process is the changes that occur in the extent, speed and accuracy of protein synthesis, modifications and turnover. These changes can lead to inefficient functional ability, including a decline in maintenance and repair, reduced capacity to respond and adapt, and appearance of abnormal phenotypes. Using the Hayflick system of cellular ageing in various cell types, such as skin fibroblasts, keratinocytes, bone marrow cells and trabecular osteoblasts, we are analysing the types, amounts and activities of proteins involved in proteasome functioning, antioxidant defence pathways and signal transduction. We have also used this system to discover compounds, such as kinetin with potential anti-ageing properties.
- Modulating ageing and preventing the loss of cell function by repeated challenge
Low-level exposure to stress such as mild heat shock seems to have beneficial effects on the structural and functional integrity of cells and organisms. In exploring this phenomenon, known as hormesis, we have shown that repeated mild heat shock slows down various biochemical characteristics associated with cellular ageing, especially the accumulation of damaged and abnormal proteins. We aim at further characterizing the beneficial effects at the levels of maintenance of stress protein profile, maintenance of signal transduction pathways, reduction in accumulation of damaged proteins, stimulation of the proteasomal machinery of protein degradation, and maintenance of differentiated cell functions during ageing.