Professor Gerald de Haan about ageing without problems

With ageing comes health problems. That is the way it is and always will be. ‘That is too easy’, says Gerald de Haan, Professor of Molecular Stem Cell Biology and Scientific Director of the European Research Institute for the Biology of Ageing (ERIBA) at the UMCG. ‘In my opinion, ageing and the development of ageing-related health problems should be slowed down as much as possible.’

We may not be aware of it, but we all try to prevent ageing. ‘This also goes for people who are not in favour of slowing down the ageing process’, De Haan says. ‘For instance, we brush our teeth using fluoride toothpaste each day. This helps to prevent early decay because fluoride makes tooth enamel stronger.’

‘Another example is applying sunscreen to protect your DNA against harmful ultraviolet radiation from the sun. Spending time in the sun each day without using sunscreen will result in rapid, premature ageing.’

Deal with it

ERIBA is a research institute at which 12 research groups focus on the underlying mechanisms of ageing. ‘People tend to think that ageing is inherent to life and must, therefore, be put up with’, De Haan says. ‘However, it is a biological process and must be caused by something. What causes the decline in the function of old cells? What causes the decline in muscle strength? And why do bones get weaker and wounds have a slower or absent healing process in people aged 95 years or over?’

‘Hopefully, understanding the underlying mechanisms of ageing will enable us to come up with solutions. Not to live up to 120 years, but to live healthier for longer. That will not only benefit us and our loved ones, but will also reduce the costs on society.’  

However, living healthier for longer also means an increase in life expectancy. Some are sceptical about this. De Haan explains: ‘Life expectancy has increased over time. The average life expectancy has increased by forty years over the last hundred years, not by coincidence but by developments in the field of biology, such as vaccines, improved hygiene and antibiotics. These are very specific interventions in biological processes. We are looking for quite similar things now.’  

Optimal metabolism

Our metabolism is among the mechanisms studied by the scientists at ERIBA. ‘One of our scientists studied mice that underwent a genetic modification to optimise their metabolism. As a result, these mice can eat whatever they want without gaining weight. In addition, they are protected against cancer and maintain muscle strength with age. Although it can undoubtedly be achieved, such genetic modification in humans is not desirable. But we may be able to discover substances with the same effect, i.e. an efficient composition of nutrients allowing each cell to be optimally fed.’

Sleeping cells           

Another research theme is senescent cells, also known as sleeping cells. These cells accumulate in all of our body tissues during the ageing process. Although they have lost their ability to divide, they are not dead. For a long time, we assumed that they were harmless.

De Haan elaborates: ‘It turns out that these cells excrete various substances that negatively affect their neighbouring cells. These include tiny inflammatory laesions causing tissue damage and degradation. In the past few years, senolytics have been developed, i.e. drugs with the capacity to target and eliminate these inflammatory cells. Elderly mice were shown to live healthier for longer after being administered this type of drug.’

‘Currently, several research projects are focusing on elderly patients with inflamed knee joints, e.g. caused by arthritis, in whom sleeping cells are found. They receive a local injection into their knee to kill these sleeping cells, after which the effectiveness is evaluated in terms of promotion of knee tissue repair.’   

Gene associated with Alzheimer’s disease          

What can we learn from all these studies? ‘I have become more and more convinced that the ageing process can be influenced in various ways’, De Haan says. ‘It is becoming easier and generally more accepted to use technology to interfere with biological mechanisms. A striking example is the ability that we have acquired over the last few years to use genetic engineering to specifically control the genetic material in cells.’

‘Suppose that we are able to discover a gene that would cause Alzheimer’s disease and suppose we could make alterations in this gene to prevent Alzheimer, without causing adverse effects. Although we may wonder if it is ethical to genetically modify someone’s cells, we will also ask ourselves whether not protecting individuals against Alzheimer’s disease is ethical either.’   

Society must be able and willing to invest in fundamental research, i.e. gaining a better understanding of underlying mechanisms of biological phenomena, according to De Haan. ‘Some people say that scientists conducting fundamental research are just fiddling about in a laboratory. And that is true’, De Haan says with a broad smile. ‘However, our ultimate goal is to allow interventions to be made. Our research is necessary to develop treatments for diseases and to develop everyday products such as fluoride toothpaste and sunscreen.’ Or indeed, to increase resilience of elderly individuals towards viral infections!