Life Goes on: Linda Partridge
Professor Dame Linda Partridge, an expert in ageing, talks to Tom Ireland about genetics, immortality and staying healthier for longer
The Biologist Vol 61(1) p28-31
Linda Partridge is a British geneticist who studies the biology and genetics of ageing. Her research looks at how healthy lifespans can be extended in model organisms and the pharmacological treatments that could keep us in good health for longer as we age. From helping to equip the lab in her convent school, to discovering genes that influence ageing, Partridge's long and successful contribution to science led to her being made a Dame Commander (DBE) in 2009. She is director of UCL's Institute of Healthy Ageing and founding director of the Max Planck Institute for Biology of Ageing.
How did you come to work on lifespan and ageing?
I was always interested in life histories – the costs of reproduction and how that can shorten life. As an evolutionary biologist, I was fascinated by those trade-offs. But what really led me to drop everything and focus on ageing mechanisms was the discovery of genes that could drastically alter the lifespan of organisms. It struck me as such a surprising result: that you could make one lesion in a gene and extend the life of an organism. That seemed to be a large flag waving in the wind to me.
How well did your convent school prepare you for a career in science?
The set-up was very well meaning – there was no hostility to science or anything, and there was some equipment. But there were no technicians and if we were to maintain the biology materials in the time between when teachers came in to teach us those things, we had to do it ourselves.
You discovered that there are universal genes found across different species which, when manipulated, can lead to increased lifespan. What do these genes normally do?
These genes produce the proteins that make a signalling network, which senses the nutrient intake of the organism and some of the stresses that it experiences. The network tunes expression of genes so that costly processes such as growth, reproduction and metabolism are matched to nutritional status. If the organism is short of nutrients or starving, then it can go into a stress-resistant mode, where costly activities are reduced.
My work owes much to a systematic search by a very clever scientist called Michael Klass. He was the first person to discover that mutation of certain genes could extend lifespan and slow ageing, working with nematode worms. In those days people were performing mutagenesis on worms (modifying their DNA), looking at how to change all kinds of traits – and Klass was looking specifically at how you could extend lifespan. His paper was published in the 1980s but it was not until 1996 that the exact identity of the genes was discovered.
Are these genes present in humans too? What prevents us from increasing the lifespan of humans?
Well, you can't mutate humans. The work being done on humans is not experimental but correlational – there are studies of people in advanced age, especially where it appears to be familial, with lots of siblings living into their 80s and 90s and beyond. They are compared to a control group to look at whether humans have the same genetic biomarkers of ageing. A lot of the work is very promising and suggests we do.
Drastically reducing the amount of food an animal has available can also restrict ageing. What is the theory behind that effect?
Dietary restriction is one of the oldest models, dating back to the 1930s. It is no small effect, either. In mice you can extend lifespan by about 50%. In experiments, generally, the composition of diet is exactly the same, but the control group has unrestricted access to food and the other group is restricted – up to 40% of what they'd normally eat. You get a dose-response relationship, down to a certain level of restriction. You don't want to starve your animals.
Eating less probably inhibits the same signalling networks that were discovered in the mutagenesis experiments. When short of food, the animals go into stress-response mode and increase the activity of processes responsible for quality control in cells and tissues. Essentially, the organism goes into 'looking after the body mode' not 'making babies mode'.
What are the side effects of such a diet?
There are surprisingly few in animal studies. Wound healing is slower and subjects are more vulnerable to certain viral infections. There are people who do dietary restriction – strangely it's almost all men – and were they to suffer from a car accident or trauma, they would probably be less able to cope with that. And, when they do get something like the flu, they have to eat up to shift it, so it is not without its downsides.
So you're working on drugs that could reproduce the effect without people having to follow a joyless dietary regime?
The idea is that we develop a pill that has this effect without any of the downsides and without people actually having to restrict their diet in that way, which realistically is off limits to most people.
Do you consider it part of your role to look at the social and socio-economic consequences of your research?
We are well aware of the demographics and economics of ageing but we are not trying to make people live longer. We want people to be healthier for longer, ideally healthy right up until they die in their sleep. Lifespan has been increasing for 2.5 years per decade since the 1900s and that is set to continue. Ageing is a risk factor in many of the long-term chronic illnesses that we are seeing more of, such as Alzheimer's and heart disease.
What does your role as a director of the Max Planck Institute for Biology of Ageing involve?
It is a new institute, part of many Max Planck research institutes across Germany. They decided ageing is a subject they wanted to look into. I got a call about six years ago from Munich and it has been really interesting setting it up from scratch. I'm one of several founding directors. It's quite basic science at the moment. The aim is to use animal and cell studies to better understand the ageing process and develop interventions to keep us healthier for longer.
If one of the institutes you direct found a way to stop ageing altogether – an immortality pill, say – what would you do with that discovery?
Whatever our views about it ethically, it is something some people would pay a huge amount of money for if it was discovered so I don't think – even if we wanted to – we'd be able to keep that quiet or control it. I suppose I just don't think it's that realistic. In mammals life seems to be limited to around 200 years at the very most, and so perhaps that might be the upper limit...evolution has had a long time to work on it.
Professor Dame Linda Partridge DBE is currently the Weldon professor of biometry at the department of genetics, evolution and environment of University College London, director of UCL's Institute of Healthy Ageing, and founding director of the Max Planck Institute for Biology of Ageing.