Aging and Disease

Biogerontologist David Gems on the senescence, medical approach to aging and how can you research the fundamental biology of aging

videos | August 25, 2020

A good place to start when talking about aging is actually the meaning of the word aging because it’s very confusing. It’s a word that has different meanings, and when people talk about aging, they can mean different things. For example, aging can refer to the passage of time, calendar aging: you grow older just in terms of how many years you’ve been alive. But aging can also sometimes refer to the changes that happen as you get older, any kind of changes, and those changes can be negative but they can be neutral or they can be beneficial. So you talk about maturational changes during adulthood: you mature and that means you’re improving, so that’s an aspect of aging which is positive.

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But as a biologist studying aging, what I’m interested in is the deterioration part of aging, and what biologists call that is senescence. So senescence really refers to all the deteriorative changes that happen as you get older. A point of confusion created by all the different meanings of the word aging is really the relationship between aging and disease, and this is a very controversial topic. According to medical tradition and what doctors that are taught in medical school, you can make a distinction between a so-called normal aging and aging-related diseases. This is a popular idea about aging, that aging itself as a process is not a bad thing, it’s normal, it’s natural, it’s kind of part of the life cycle whereas the bad part of aging is the diseases of aging. The reason why we want to understand aging is that at the present time it’s become the main cause of disease in the world, so most of the folks who watch this little movie are going to eventually die as a consequence of aging: they’ll die from things like cancer which is largely a disease of aging, they’ll die of dementia, cardiovascular disease like stroke or heart attack or chronic obstructive pulmonary disease and many many other kinds of disease. Dementias, Alzheimer’s disease, Parkinson’s disease, all of these are all part of the process of aging.

According to the view of some, they would argue that if you’re studying aging, if you’re trying to work on aging and make use of the science of aging, what you want to do is to allow people to age naturally and normally but remain free of the diseases of aging. So there’s kind of the good aging and the bad aging. I think my understanding of that notion is really a pragmatic approach to aging which has been developed by doctors. If I go to my doctor, I’m in my late 50s and I say, look, I’m worried because my eyesight’s not so good, there’s something wrong with my eyes, and she’ll say, no no no, you’re in your late 50s, it’s just normal aging of the eyes. Or if I say, my skin’s wrinkling, bit worried, and she’ll say, no no no, that’s just the age, it’s just not normal aging of your skin.

But from a biological perspective, from the point of view of biological processes there isn’t really any basis for this division between diseases of aging and kind of normal aging.

Here we’re talking about senescence, we’re talking about all of the different aspects of senescence: I’m not talking about maturation, I’m talking about deterioration. The fact that my eyesight is failing is because of deterioration of my eyes, or if my skin is wrinkling, it doesn’t hurt, it’s not a disability or anything, but from a biological perspective what’s happening here is the beginnings of essentially the degeneration of my skin. As I get older, it will become more and more severe, and my eyesight will get worse and worse.

So the division between kind of normal aging, normal senescence if you like, and diseases of aging actually in scientific terms has no real rationale behind it. In fact, this division between aging and disease is something that is quite permeable. Over the years increasingly conditions that are part of aging which were once viewed as normal aging, such as muscle wasting or sarcopenia or even Alzheimer’s disease are now regarded as diseases. When I was a boy, Alzheimer’s disease only referred to the hereditary Alzheimer’s disease which you develop when you’re in your middle age, and the later dementia was called normal senility, so you wouldn’t say grandma’s got Alzheimer’s disease, you’d say grandma’s just a bit senile. That’s just nature taking its course.

From that point of view this division between normal aging and diseases of aging has no rational basis, and in fact, all of it is essentially pathological. The whole process of senescence is a pathological process, it’s all kind of a disease state. Looking at it from that point of view, I don’t think scientifically it’s a controversial thing to say that senescence is fundamentally a disease process. When I’m thinking that my eyesight started to go, my skin started to wrinkle, these are just the beginning stages of a massive disease process that eventually I’ll die from.

So what’s sometimes stated that scientists working on the biology of aging should be doing, which is that they should be looking to treat aging-related diseases but not aging itself, really makes no sense whatsoever. All of it is bad, so intervening in any part of it is something that what we should be doing, ethically it’s the right thing to do, to treat the whole aging process.

And I think this false dichotomy between aging and disease is something which is and has been a kind of an obstruction to investigate, to research on the biology of aging. I’ll just give a kind of a slightly silly example: at the moment the Medical Research Council which is one of the main funding agencies in the UK don’t really fund research on the basic biology of aging because they say aging is not a disease whereas Biotechnology and Biological Sciences Research Council which is the main funding agency for biology will be reluctant to fund you if you say you’re interested in how aging gives rise to aging-related diseases because they say they don’t fund disease.

And similarly, the Age UK is the main charity for raising money for the elderly, it’s a very good charity. But when the charity formed from the merger of two smaller charities, they stopped funding research on basic biology of aging. My understanding is that that’s partly because they found the notion of viewing aging as a disease as something rather unwholesome and even sort of discriminatory, and somehow disrespectful to the elderly. So I think this is something that has caused quite a lot of confusion.

So aging therefore is really a disease syndrome, it’s really something which is the cause of now most of the diseases worldwide. It’s therefore very important to really understand what is this process of senescence, why does it happen, what causes it which makes it extraordinarily interesting to work on as a scientist. You’ve got what is really the cause of most of the disease in the world now, and yet it’s really not understood, it’s remarkable. So one of the reasons why it’s not well understood is because it’s a very very complex process. It’s almost certainly something which is controlled from our own genome, and it’s sort of defeated really the tempts by scientists to understand it.

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The approach that my lab and quite a lot of other labs also take is the reductionist approach. The idea is to take a very very simple organism, as simple as you can find that actually exhibits this phenomenon of senescence, and try to work out thoroughly and completely the nature of the biology of aging in a simple organism. So what we work on here is an animal but it’s very small and very very short-lived, and it’s a type of worm, it’s called Caenorhabditis elegans. It’s a nematode worm, they live in the wild on rotting fruit and rotting plant stems. They are a complex animal, they have a nervous system and a reproductive system and behaviour and so on, but they grow old and die within only about 2-3 weeks.

So really this is the goal of the research. The idea is that if you could solve aging in this one simple organism, then you would be able to discover the basic principles that underlie aging as a process. We’re really looking for very very fundamental principles, similar in their level of generality to things like the germ theory of disease of Pasteur and Koch. There’s something that gives you a fundamental basic insight into the nature of aging, so that’s really what this work is trying to achieve. So if we understand it in this simple organism, then I think that should open the way to really being able to understand where Alzheimer’s disease comes from, why when you get old, you get osteoarthritis, what happens to the lungs as you get older, why do you develop chronic obstructive pulmonary disease, are there general principles that underlie how senescence, how aging is giving rise to all of those diseases. And then hopefully through that one we can find ways to prevent those illnesses from developing in the first place.

What’s exciting working with the animal models is that you can actually intervene in aging in these simple animals, you can actually manipulate the aging process in such a way that you can speed it up or you can slow it down quite considerably. And when you do that, you can slow down all of the funny diseases that the worms get as they get older and prevent them from developing, so the animals stay healthier for longer and then they live longer. Somehow in the worm there has to be some big secrets about the nature of aging. I and quite a lot of other labs around the world are all kind of pursuing these secrets, they’re like a kind of Holy Grail for the biology of aging, to have some fundamental knowledge of aging, of what’s actually causing it.

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Professor of Biogerontology, University College London
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