Stored tissue samples can show how people age

Breaking new ground 12. jul 2018 4 min Professor Rudi GJ Westendorp Written by Morten Busch

Hospitals use samples of cells and tissue to determine whether people have diseases such as cancer. In Denmark, hospitals have taken thousands of samples every day, some of which are stored under high security at the Danish Pathology Databank. A large-scale Danish research project is seeking to discover the difference between people who die early and people who live long and to become better at diagnosing and treating people individually.

Many researchers forecast that most people alive today will live more than 100 years. But can we really predict who will live a long and happy life and who will develop disease and die early? A Danish-led international research project wants to answer this question, and the project will use a simple tool to solve this difficult question: time.

“Many people believe that we can answer many questions by analysing genetic material from living people, but the truth is that that many more answers lie hidden in the past. We have therefore started to analyse almost 14 million tissue samples collected in Denmark since the 1960s. We will not only find answers based on people who became ill but, equally importantly, based on who remained healthy,” explains Rudi Westendorp, leader of the project and Professor, Department of Public Health and Center for Healthy Aging, University of Copenhagen.

Storage generates value

The researchers will seek to determine how people age based on the Danish Pathology Databank. The Databank receives about 750,000 new samples every year from Denmark’s 14 departments of pathology, and even though the samples are stored because disease is suspected, the research goldmine is in a completely different place according to the researchers.

“The tremendous value is that we have samples from people who were ill and people who were healthy. With such a volume of samples, we are likely to discover the characteristics of the people who became ill and of those who remained healthy. In addition, some people had multiple samples, so we can also see how the tissue develops over time as an individual ages.”

Rudi Westendorp’s goal is to create electronic life histories based on the accessible data to show how people age and how ageing can make people ill. This is only possible because Denmark has systematically collected samples for many years that can be linked to the Danish ID number, which enables samples to be associated with a person’s life history while simultaneously maintaining the anonymity and privacy of each individual.

“Denmark has unique material in the millions of samples stored that are ready to be analysed, and it would be silly not to do this. Like most good wine, which becomes even more valuable when stored, each of these electronic life histories contains information that can give us greater insight into the diseases on which we should focus among people with various genetic profiles.”

Genes are one factor but not the only one the researchers will explore. In addition to the genome, the project will address the physical, social and environmental circumstances in which people were brought up and grow old – information that is stored in the archives of Statistics Denmark.

“This is the other side of the coin. The environment is equally important in studying disease and health. Think of smoking and lung cancer. There is almost no risk in not smoking. On the other hand, only one in three smokers develops lung cancer in the long term. So genetic action is important, but it critically depends on the environment in which it is expressed.”

A huge opportunity

The Danish Pathology Databank is a national registry that contains information on all tissue and cell samples taken in Denmark’s healthcare system. Today, the Databank contains data on tissue samples going back to 1970 and the diagnoses given to people suspected of having cancer and immune system, inflammatory and degenerative diseases and disorders.

“The reason why nobody could do this before is because we finally have adequate computer power and analytical methods to link the pathological findings with molecular biomarkers and the diagnoses of these millions of people. This means that we can now see connections that no one could see before.”

The researchers are especially seeking the mechanisms of ageing, specifically because old age and disease are very closely linked. Previously, researchers had suggested hundreds of possible biological mechanisms that were considered to influence ageing. The problem is simply that the mechanisms that could be the most important could never be confirmed with any certainty.

“This research was carried out on fruit flies and zebrafish, which have both many similarities and many differences with humans. Nevertheless, modifying people’s genes to investigate these mechanisms is not ethical. The information in the Databank therefore presents a huge opportunity to study human ageing for the first time, and we strongly suspect that we will discover the most important factors and completely new biomarkers and mechanisms.”

We still do not know the most important part

Although the possibilities are endless, the researchers involved in the project have taken a solemn oath to safeguard the vulnerable data. According to Rudi Westerdorp, the future of Denmark’s unique registries strongly depends on mutual respect between citizens and the state. All the data in the project will therefore be stored behind the securely locked doors of Statistics Denmark.

“Based on the current Facebook controversy, we emphasize that this research will not focus on getting a few rapid and easy results that can make us famous. We are building a rock-solid platform and some structures for the future that we can use to create value from this unique registry and databank of biological tissue. We have succeeded if we can retain the confidence of the general public in Denmark.”

Naturally, in addition to building a platform for the future, the researchers hope that the unique collaboration between statisticians, epidemiologists, pathologists and molecular biologists will harvest the low-hanging fruit in the form of unique biomarkers and mechanisms that seem to play a major role in ageing and disease. However, the researchers cannot yet formulate the questions that will lead to the most important answers sought by the project.

“Even though we think we have made great strides in our ability to extract information from biological data, nobody knows what opportunities will arise in the future. A tissue sample is the most efficient way of storing biological data. Thirty years ago, DNA analysis could only be performed in a few samples using a handful of markers. Nevertheless, samples from that time were retained, and today we can see the DNA – the blueprint of life – functioning in slow motion. We cannot imagine how people will be able to use our platform 20–30 years from now.”

The Novo Nordisk Foundation awarded Rudi Westendorp a 2018 Novo Nordisk Foundation Challenge Programme grant for the project Harnessing the Power of Big Data to Address the Societal Challenge of Aging.

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