Revealing processes behind ageing
A "mission impossible" solved in two years. Ten years ago, Maria Eriksson was asked to find the gene for a rare genetic disease not much known about.
"Within two years we discovered the gene and the genetic mechanism for this disorder," says Maria Eriksson, today a group leader at the Department of Biosciences and Nutrition. Her team is currently expanding the knowledge about this disease, called progeria, and using this knowledge to understand more about the factors of normal ageing. Progeria is a very rare but severe disease that causes several of the classic ageing features.
Maria Eriksson and colleagues are looking into genetic mechanisms of ageing. From left: Ylva Rosengardten, Eva Schmidt, Tomas McKenna, Maria Eriksson, Diana Grochova and Sofia Rodriguez
Already within the first years of their life the progeria carriers develop symptoms and all the affected children suffer from osteoporosis and atherosclerosis. The progeria children die in their early teens, usually from myocardial infarction or stroke. The mutated gene in progeria that Maria Eriksson discovered is called LMNA and encodes for the proteins lamin A and C which are essential for nuclear stability. The mutation leads to a defective lamin A protein called progerin.
On and off mice
The main tool in Maria Eriksson's research is an animal model that she brought with her from the US to Karolinska Institutet. The model is an inducible tissue-specific mouse.
"We can turn on and off the progeria mutation in a certain tissue and at a certain point in time. The tissue-specific technique is especially useful when studying multi-systemic severe disorders, since it enables us to study the tissues one by one."
When Maria Eriksson and colleagues turned off the gene for progeria in their model system with fully developed disease in skin, the symptoms repealed within 13 weeks.
"We have proven that it is possible to reverse progeria as long as you can get rid of the mutant protein," says Maria Eriksson.
This discovery gives hope for recovery and future treatment for a currently untreatable disease.
The link to normal ageing
Another branch of the research of Maria Eriksson's team is to look into the genetic mechanisms of normal ageing. The research team has performed studies where they have aged normal human cells in cultures from healthy young persons,
from persons with progeria, and from elderly persons.
Comparing these three groups, they could show an increase
of progerin in the latter two, but not in the cells from the younger individuals. This indicates that there is a similar genetic mechanism in progeria and normal ageing.
"Ageing is a very complex process which not much is known about. But we have found a direct link between normal ageing and progeria! This emphasizes the usefulness with studying a very rare disorder to find information about more common phenomena in the human body."
Text: Jill Jönsson