Prof David Gems - Healthy ageing

Kat - It's a sad fact of life that we all get older. And it's not just wrinkles and grey hair - there are many diseases of old age creeping up on us, from dementia and arthritis to cancer and heart disease. Cheery stuff. At the UCL Institute of Healthy ageing, researchers are investigating the genetics of ageing, and how understanding the fundamental biological changes that happen as we age could help us live longer, healthier lives. I spoke to David Gems, assistant director of the Institute and professor of biogerontology, and started by asking him what we mean by "ageing".

David -   The word 'ageing' is a very slippery term that causes a lot of confusion because it means multiple things.  I mean, ageing can mean just that you gain more years.  In that sense, anything, everything, ages - everything grows older over time.  Ageing can also mean in a broad sense any kind of change that happens over time.  So I mean, here's my coffee and you could say that as my coffee gets cold over time, that's an age change. 

And so in people, age changes can include all sorts of things.  I mean, that can include maturational changes, changes in temperament and all sorts of things.  But the ageing that I'm interested in is the deteriorative aspect of ageing which biologists sometimes call senescence to try to be clear about it.  So, the interest here is really in the biology of senescence.  Senescence is something which is really not understood in terms of its biology.

Kat -   This is the gradual conking out of our cells?

David -   People working on the biology of ageing still argue about how to even define ageing.  There are different ways of defining it.  I would say, the thing which is really characteristic about ageing, that is senescence, is the development of pathology, pathologies that come from within.  They're not caused by external things like germs or something.  They're actually coming from within your own body.  So, there's some sort of process which gives rise to a load of pathologies.  Those pathologies are - in the developed world - really the main cause of death.

Kat -   So, these are things like dementia, heart disease, all these kind of problems.

David -   Yeah.  I mean numerically, the overwhelming cause of disease in the developed is ageing itself.  I mean, there are a lot of aspects of ageing people don't really think of as ageing, but they are.  So for example, most cancer actually develops as part of the ageing process.  Dementia as you mentioned, type 2 diabetes tends to get worse with age.  Yeah, dementias like Alzheimer's disease, Parkinson's and others.  I mean, it's bewildering how many pathologies there are.  It's terrible, really.

Kat -   And depressing.

David -   Yeah, right.  I guess that's the human condition.

Kat -   So, what do we know in terms of say, human bodies or other animal bodies - what's going at a cellular or a genetic level as cells or organisms age?

David -   As a biogerontologist, working on the biology of ageing, I can say with some authority that we really don't know and it's actually one of the things which is very exciting about working on biology of ageing.  It's the main cause of disease in the world.

Kat -   And no one knows anything!

David -   Well, there's lots of ideas and the state to play at the moment is - there's a lot of research at the moment on the fundamentals of ageing, but there isn't really an agreement about what sort of process ageing is.  So, I think traditionally, most of the ideas about ageing over the last 50 years have been based around the idea of ageing as a kind of a 'wear and tear' type process.  So, it's a bit like machines that wear out.

Kat -   Your parts get a bit rusty, everything stops working quite as well.

David -   Yeah, 'rusty' exactly puts a finger on it because rust is metal oxidation and one of the ideas is that we are living in this high oxygen atmosphere and oxygen burns.  So, you have a process of oxidisation in living systems, just like you do in mechanical systems.  But I think in the last 5 years or so, there are many different theories based around damage of one kind or another causing ageing and how it happens including telomere shortening, chromosome shortening.  That's a kind of a damage theory.

Kat -   Yeah, your chromosomes just getting shorter and shorter and then they can't do anything else.

David -   That's right and the cells kick out of the cell cycle.  I think at the moment, I really think there has been a kind of a watershed for this ageing damage paradigm where people are starting to wonder whether it's really true and there are some alternative theories that are appearing.  So, it's a very exciting period scientifically in terms of paradigm shifts and so on, I think.

Kat -   So, if you say there's lots of different theories, what one is your favourite one perhaps, and what are you trying to do in your lab to understand this process a bit more?

David -   So, the main approach that my lab and quite a few others have been taking to try to figure out ageing is to look at the genes that control ageing.  So, you don't really need to do any science to know that ageing is controlled by genes because different animal species have different life spans - that is their maximum lifespan.  So, if you take for example humans and our closest relative, the common chimp, our maximum life span is about double that as a common chimp.  So, we've evolved recently a much longer lifespan.  It just shows how genes control ageing. 

So, what a lot of scientists are doing is using very short-lived animals like fruit flies, like these nematode worms, which is what I work on.  Their proper name is Caenorhabditis elegans, and they're great to study because their life spans are very short.  So, C. elegans only lives about 2 or 3 weeks.  So, you can look at the genetics of ageing in C. elegans.  You can look for mutants for strains of worm where they have change genetic changes which have different rates of ageing.  Either they age more quickly or age more slowly.  They're the more interesting ones because they live longer.

Kat -   So, I guess in a worm, if you're getting one to live maybe a week longer, that's a really significant increase on a worm's lifespan.

David -   Yes, it is.  I mean for example, there's a group in Arkansas who are currently the record holders for extending lifespan in worms.

Kat -   I love that it's competition.

David -   Yeah.  It's true, I feel strongly because I had the longest-lived worm strain at one point.  It was a 7-fold increase in lifespan.  These guys in Arkansas, they got 10-fold increase in their lifespan.  But it's only a couple of months of extra life.  If you translate that to a human being, it's hard to know what that means.  I mean, that could mean...

Kat -   That's 700 years or...?

David -   Is it a thousand years or is it an extra 4 months?  It's actually hard to know how to translate it.  The bottom line though is that what this tells you is that ageing is actually plastic and that's so important.  I think almost all the discoveries that have come out of this lifespan genetics, that basic observation that ageing is plastic.  It's not fixed.  It is something that is alterable.  It's very, very profound and has shaped a lot of thinking in the field and ideas about what the field can do. 

So, in terms of what we learn from that, what we hope was that we find the gene that controls ageing and then we find out what that gene actually does, what protein it makes and what's the kind of biochemical cellular process that that gene is affecting.  And that should lead us to ageing and what ageing is.

Kat -   How long would you like to live for?

David -   I don't know.  I mean, do find that one thing about working in this field is that I tend to always want to not think about the fantasy aspects but think about the realities.  I mean if I had a choice, I guess I would like to be able to live long enough so that I could choose when to end my own life and I don't know how long I would want to live.  I think probably a lot would depend on how capable I was of reinventing myself and changing.  I mean, it's unanswerable.  Who knows, who knows?

Kat - That was Professor David Gems from UCL.