Ageing Bang Goes the Theory

Welcome to Bang, unravelling the science behind the issues

that impact all our lives.

This week we're tackling ageing.

People are living longer.

Back in the '40s, life expectancy in this country

was set at around 67 years of age.

Now it's 80 years of age.

And the consequences of that are rarely out of the news,

with stories about employment, the cost of pensions and health care.

Living longer also means that more people will

suffer from age-related conditions

like dementia and osteoporosis.

So the big question is

if we're living longer, can we live more healthily too?

Tonight on Bang, the science of ageing.

Sir Terry Wogan joins the team to sort

fact from fiction in the news headlines.

Vitamin E slows down Alzheimer's.

Vitamin B is a sovereign remedy.

According to this headline, "Statins halt Alzheimer's."

There's so much information.

Three generations of the Hall family take a microscopic

look at how our muscles and bones change as we get older.

As I look at Molly, I'm thinking,

"Well, what's she doing right that I'm not doing?"

Or maybe it's too late.

And Liz meets a scientist on the verge of a major discovery.

Using live human nerve cells is completely

transforming our understanding of how to find a cure.

This is the scientific process at its best.

MUSIC: "My Generation" by The Zimmers

# People try to put us down

# Talking about my generation

# Just because we get around. #

People are now living longer than ever...

..and we spend millions trying to cover the cracks

of our ageing exteriors

but we all know it's what's on the inside that really counts.

As we age, our muscles, our bones and our brains

become more and more vulnerable.

So, taking a look inside the body,

we're joined by three generations of the Hall family.

19-year-old Molly,

her 52-year-old mum, Judith,

and granny Mary, who's 88.

So, what we're going to do

is to take a look at the ageing process on the cellular level

and we're going to show you, with people of equivalent ages,

what is happening right inside your muscles.

We all know we lose muscle mass and strength as we age

but what actually is this deterioration?

This is a muscle section from a young person like Molly

and what you can see is that there are individual muscle fibres here.

The most important thing

is you see that pretty well each fibre looks the same.

Hidden inside are the mitochondria -

the power plant within every cell that converts our food into energy.

Doug has stained the cells to highlight mitochondrial damage.

A cell with healthy mitochondria will show no bright colours.

Now, what happens when we go to Judith's muscle biopsy...

I'm quite shocked, actually, how the differential between Molly and me.

I'll get you a chair!

..we'll see that there are changes that have already started to happen.

You can see that everything isn't the same colour.

Different colours indicate different types of damage in the mitochondria.

Doug believes that could be an important

factor behind shrinkage and cell death and that's what

leads to the loss of muscle mass we see as we get older.

So how well has the mitochondria survived in someone of Mary's age?

This has got even more marked changes, which is associated with

mitochondrial damage.

It now looks like Christmas lights, doesn't it?

Someone of Mary's age could have lost over 50% of their peak

muscle mass, leading to impaired mobility and poorer quality of life.

It's important to understand

the process is going to happen to everybody.

We're all going to age.

Is there anything we can do to sort of mitigate this process?

Well, one of the things we know is that if people do regular

exercise you can actually move your muscle back to something

many years before.

So you could almost suggest that you could almost go back

to there or, in Judith's case, might even be able to go back to that.

While some muscle wastage is an inevitable part of ageing,

a lot of it comes down to the fact that we tend to be

less active as we get older.

But regular exercise can build up muscle up to five times faster

than it wastes away.

-I like the fact that you can still do something.

-Absolutely.

It's not too late to make a difference.

But it's not just our muscles that get weaker with age.

One in five men and one in two women over the age of 50

will break a bone.

Hips and arms make up over half of the bones broken in over-60s

and the consequences can be very serious indeed.

Every month, 1,100 people die as a result of hip fractures, so

bone health and osteoporosis are a big concern for the elderly.

So let's see what happens to our bones as we age.

Each member of our family have been put in a DEXA scanner.

This machine beams low doses of X-ray at the patient's body

giving us accurate measurements of their bone density.

Right, Molly, it's time to get the results of your DEXA scan

so shall we just bring them up on the screen?

Looks a bit odd, doesn't it? Inside of you.

This is Molly's.

Someone Molly's age should be somewhere in the light blue area.

And we can see that you're up there.

So your bone density is well above the average we'd expect.

That's good. I'm happy about that.

Judith has a lower bone density than her daughter,

which we'd expect because

you're older.

As I look at Molly, I'm thinking,

"Well, what's she doing right that I'm not doing?"

Or maybe it's too late.

From the moment we're born, bone density slowly increases,

reaching a peak at about 30,

when it levels out then starts to decline slowly.

At around 50 years old, it dips sharply, but only for women.

The changes for men aren't as dramatic

because they don't have the menopause.

If we go to the other age of 80-something...

Mary has lost around a third of the bone density

she would have had at peak bone health.

As we age, strong bone can become a thin lattice

and this is one of the reasons that older people are

so susceptible to breaking bones.

But there's good news for Mary.

If we look at the spine, actually, your bone density is a lot higher,

well above expected for age, at the spine.

I'm top dog.

Mary has led an active life, including working on a farm,

and it looks as if that has paid off.

-So, you've come out of this very well.

-Yes.

I'm going to make sure I follow in Granny's footsteps.

Not Mum's.

THEY LAUGH

So what causes this decline in bone density as we age?

First, we need to understand what bone actually is.

This obviously is a bone. It's the long thigh bone that

runs from hip joint to your knee and it's called the femur.

And it looks pretty much like it's made up of one material - bone.

But it's actually far more complex than that.

There are several types of bone tissue but the structural

part of bone is essentially made up of two very different materials.

The first is collagen, a protein that's found in many

different forms in our skin and in various tissues in the body.

And it's an incredibly tough and elastic substance.

In our bones, it provides flexibility so, just like these suspension

systems in these old cars, it allows our bones to withstand

the incredibly dynamic forces that our bodies experience every day.

'But as a material to help you stand up, collagen is rather useless,

'which is why bones need a second, harder, material.'

It's a mineral called calcium phosphate. Now, it is pretty hard

but it's also incredibly brittle. A bit like this glass.

Now, on their own, neither would be any good for a skeleton.

If my bones were made of all collagen they'd be wobbly

and unstable. If they were made of all calcium phosphate

they would shatter pretty easily.

'But it's when those two very different materials combine

'that something remarkable happens.

'This old car windscreen is no more than two layers of glass with

'a see-through layer of rubber sandwiched in-between.'

The result is a rigid composite material that won't shatter easily.

A bit like our bones.

In fact, healthy human leg bones can withstand compressive

forces of over a tonne.

Bones are as alive as any other part of our bodies.

They're constantly changing, renewing and repairing themselves.

All through life, bone material is being

released from our skeleton, with new bone being laid down.

And the released bone matter is broken down, and its minerals,

like calcium, are released into the body in a process called resorption.

In fact, by the time you reach your late 30s, your entire

skeleton will have been resorbed and reformed five or six times.

And that's a process that will go on until the day you die.

From our 30s onwards,

bone formation no longer keeps up with bone loss, so our bones

lose density and mass. Just like we saw with the Hall family.

And, unfortunately, for women past the menopause, this loss

is three times as fast as it is for men.

So what causes this huge difference in bone density

between men and women?

Well, in part, it's down to the hormone oestrogen.

Oestrogen is the primary female sex hormone.

It's present in men as well but it's in much lesser concentrations.

The cells that break down and resorb our bone are called osteoclasts

and oestrogen helps to slow down their activity.

But as we women age, we produce less and less oestrogen, with our levels

dropping far below those of men by the time we reach our menopause.

And so the suppressing effects that the oestrogen

has on the osteoclasts are greatly reduced...

..meaning that more and more bone is resorbed,

outstripping the amount of new bone that is formed.

But, the more you use your bones, especially with high impact

exercise like running, the more bone growth is stimulated.

And regular exercise

can decrease your chance of breaking bones by 50%.

I've been running since I was late 30s, I think.

Now I swim three times a week and run twice a week.

On a Monday and a Tuesday, I go to yoga on the bus

and then I run back against my watch.

The average age here is 70. There's 350 years of talent here!

However, a healthy body is nothing without a healthy mind.

Today, over 800,000 people in the UK are suffering from some

form of dementia and the chances of developing it increase

dramatically with age.

There are up to 100 different types of dementia,

which is the collective term for symptoms caused by diseases

like Alzheimer's, vascular dementia and sometimes Parkinson's.

In most cases, dementia is a result of the loss of connections

between brain cells, or brain cell death.

Memory loss, difficulty in problem solving and changes

in personality are just some of the most common signs of the illness.

The priority for scientists

is to work out exactly what's going on inside the brain.

So I've come to Newcastle University's Brain Tissue Resource

to find out.

Do you know, I've done many things in my time

but I've never held a brain?

There's a real softness to this.

You know, it's very delicate.

This brain is typical of a healthy 80-year-old.

I still find it very difficult to believe this is

responsible for everything I think, everything I decide to do,

for my memories, for my personality.

And here is a brain of an 80-year-old with Alzheimer's.

It's about 10% lighter.

This feels very different to me.

There's a sense that somehow the texture of this has been altered.

I mean, certainly the brain is a lot lighter

because we know we've lost nerve cells from key parts

of the brain that will make the whole brain function differently.

Or at least it would during life.

As the cells die, whole parts of the brain shrivel up

and one of the first areas to shrink is

the hippocampus at the bottom of the brain,

a critical area for memory.

We know that by the time somebody first shows their first symptoms of

memory impairment, short term memory usually, that the

disease process has been going on for a little

while before that, perhaps 5-10 years. So, by the time somebody shows

their first symptoms, the pathology and changes are well established.

For many people over 60, the fear that they may be developing dementia

or could do so in the future is a major worry.

And it's rarely out of the press.

Well, let me break it to you gently. The news is not so good.

One in three of us over the age of 65 are going to die with dementia.

And it's even worse for a man of my advanced years at 75.

By the time I'm 85, there's a 50-50 chance

I'm going to develop dementia.

'Well, that scares me so I want to know

'if there's any way of preventing it.

'And one thing that keeps popping up in the papers - diet.'

Numerous reports have shown that this Mediterranean diet

is going to do you a power of good.

Improve your brain function, your general health,

less chance perhaps of developing Alzheimer's disease.

But diet isn't the only suggestion hitting the headlines.

In fact, hardly a week goes by without some headline saying

that there's a new magic bullet.

Vitamin E slows down Alzheimer's.

Vitamin B is a sovereign remedy.

Here's another one extolling the virtues of coconut oil.

And then we have the magic statins.

According to this headline, "Statins halt Alzheimer's."

There's so much information

and...I haven't a clue!

But I want to find out

and I know a scientist who might just help me unravel all of this.

So, vitamin E, first of all, can that do any good?

Well, there was some research published recently which

suggests it might be able to do some good, however

very, very high doses were used and, actually, many doctors don't

recommend that people should be taking vitamin E at such high doses.

'And Simon also tells me research into vitamin B isn't

'conclusive yet and

'the effectiveness of coconut oil seems to be hearsay.'

I think it would be wonderful and amazing to think that the

answer to dementia would be found in a small bottle such as these.

Something safe, something cheap.

Unfortunately, I think, the evidence at the moment doesn't back

any of this up, certainly enough for people to start taking these.

'But what about statins,

'the so-called wonder drug for the over-50s?

'Statins can help lower cholesterol

'but what is behind the bold headline that they are also

'effective against Alzheimer's?'

Now, this was about a study in mice.

Not really worried about Alzheimer's in mice.

Well, that's right. Mice don't get Alzheimer's disease and the mice

in these experiments didn't have the Alzheimer's disease

-that we would know.

-Is that any good to us, then?

It suggests that there could be a possible mechanism.

What certainly isn't true is that

statins halt Alzheimer's disease or other dementias.

'So have there been any trials in humans?'

There have been some reports recently but I don't think

it's conclusive yet and I think we'll have to wait a little

longer until we have more evidence before we can say for certain.

Is there any prospect that we're going to get

a treatment that will work for Alzheimer's?

I think there is certainly a good deal of optimism that we will

manage a treatment that does something to Alzheimer's by 2025,

and it may even be before then.

Well, thank heaven for that!

A little light at the end of the tunnel.

'In the meantime, we'll just have to wait.'

So, I'm afraid no easy solution.

And, although I normally stick to an Irish diet, I think

in future I'd better take the advice of better men,

and go for the olive oil, the vegetables, the fruit.

How hard can it be?

We've been told for some time that exercise

and diet help to prevent disease

and there's a lot of research to back this up.

Here's just one example.

In a particular study that lasted 30 years

and monitored the health of almost 2,500 men in Caerphilly

in Wales, the results were very interesting.

The data suggest that those that led a much healthy lifestyle were

substantially less likely to develop strokes, heart disease or diabetes.

And the risk of developing dementia was reduced by about 60%

and, for those men that did go on to develop dementia,

the onset was delayed by up to seven years.

Although ageing at the moment might be

perceived by many as an inevitable downhill process, you can

still have some control about how steep the hill is.

Nevertheless, caring for and treating those with dementia is

currently costing the UK over £23 billion a year.

That's more than heart disease, cancer or strokes.

And figures are expected to rise to 1.7 million people by 2050,

which is why David Cameron recently pledged at the G8 summit to

increase the amount spent on research.

The aim of trying to find a cure or disease-halting

therapy by 2025 is within our grasp.

And it may be closer than we think.

'At the Gurdon Institute in Cambridge there is some astonishing

'research that I can't wait to see for myself.'

Up to now, the only way to

study the disease has been either look at brains from people

who had died of the disease, which is useful, but you're not

seeing the disease, you're seeing the end point. So we needed a way

to look in human nerve cells in real-time as the disease progresses.

So they did something amazing.

Building on pioneering research done here 50 years ago,

they took stem cells, the sort of cell that can form any other

type of cell, and made them develop into brain cells.

They're all talking to one another and they talk the same way they do

in your brain or my brain. These are live.

I know you do this every day, right. It's kind of... You're used to

this but it's mind-blowing what's going on in this laboratory.

The fact that you can do this is humongous, isn't it?

Yes, it's great fun. I mean, this is two-dimensional.

-Great fun!

-No, it is. But also, the other thing

we're working on is, you know, the brain

is three-dimensional, so we're also busy trying to make this in three

dimensions as well, just get all the architecture, so making mini brains.

I mean that's a little bit crazy. Are you telling me that,

-in a Petri dish, you can actually have a 3D brain?

-Yeah.

'Rick uses stem cells from someone who is genetically almost

'certain to get Alzheimer's

'and he can effectively grow the disease in his lab.'

If you look at the brain of someone with Alzheimer's disease

and cut a little slice, you can find two bits of pathology

and they are called plaques and tangles.

'For the first time, Rick can now watch them as they form.

'Plaques are made up of tiny fragments of protein,

'which stop the nerve cells communicating with each other,

'causing the symptoms of dementia.'

This is plaque formation that is characteristic of Alzheimer's.

Exactly. So this is completely abnormal.

So these are very sick neurones.

'Tangles are involved in the spread of the disease.

'They are made up of a different protein,

'present inside the brain cells.'

In the disease, it actually just starts accumulating and forming

these big, long tangles which essentially strangle the neuron.

But the other thing it does is we all now think it

spreads from neuron to neuron, making the other neurons sick.

'In another lab, Rick can

'watch the tangle protein passing on the disease.'

It's not like an infection, where a virus or a bacterium...

This is a protein - the simplest thing you could possibly use.

This is your body turning on itself.

Why is it important to understand this?

We think this is a fundamental mechanism how the disease

spreads through your brain.

And it's only because they can grow living brain cells that

they've been able to see the disease spreading.

This means Rick and his team can, for the first time, test a whole

multitude of different drugs on live human brain cells

and watch the effects on a cellular level.

At the moment, over 1,000 drugs are being investigated.

How long before you are able to say to the pharmaceutical industry,

"This is one that is looking exciting - start making it?"

We're very close. We're now in the process of working out

which one or two to really put our money on.

That's within this year, effectively.

-Within this year?

-Yeah.

-That's exciting stuff.

A life-changing treatment for Alzheimer's is now closer than ever.

You know this is a scientific process at its best.

Ground-breaking research that was carried out 50 years ago has

now inspired others to apply that knowledge to find

a cure for a debilitating disease and it's a very exciting

time for Alzheimer's research because this breakthrough, allowing

us to understand the disease at its early stages using live human nerve

cells, is completely transforming our understanding of how to find a cure.

The goal is to be able to live healthier lives

without diseases like osteoporosis and dementia.

But how long could we live?

How much longer would we want to live?

There is some very intriguing research that's exploring

what it actually is that limits our life span.

Instead of trying to understand

human ageing, if you could just

take a really simple animal,

the simplest animal possible that shows ageing,

and then figure out what ageing is in that

organism, that at least would give you a start.

Professor Gems has been studying worms.

He's working with the microscopic C elegans roundworm.

Each Petrie dish contains thousands.

C elegans were the first multi-cellular organisms to

have their entire genome sequenced.

They only consist of 1,000 cells

but, amazingly, they still share 40% of the same genes as us.

Their life spans are really short.

They actually only live 2-3 weeks so they actually grow old and die

within 2-3 weeks, which, for a scientist, is absolutely great.

So you can find answers very quickly?

Well, that's the point.

An astonishing discovery showed that

C elegans with certain genetic mutations were living longer.

So what you can do is you can isolate worms where one of the genes

is busted and the worms live longer.

How long has your most long-lived worm lived?

Well, my longest-lived worm... I was very proud of it at the time.

It was a male one that lived about seven times longer than normal.

So normally it would be living about 2-3 weeks

and it was seven-fold greater than that.

So, if it was a human being, it would be living to 800-900 years.

Intensive investigations came up with a revelation.

The genes that control ageing in the worm, it turns out that those

same genes actually exist in humans and, in fact, there is

now evidence that at least some of the genes that control ageing

in the worm may even be controlling human ageing,

-which is very exciting.

-It's extremely exciting.

The implications for us could potentially be enormous.

I've got to ask you, you know,

how long before, "We've found it, the answer to ageing?"

Boy, that's a hard one. The thing which remains unsolved is

really how those genes are actually producing the increase in life span.

That's the great big unknown,

which is what actually is ageing as a process?

What exactly is it that we die of? That's really an unsolved question.

The science of ageing is a surprisingly recent

area of research and it's only

since the '80s that people have been thinking about it as a disease.

By taking that approach

and by studying simple organisms like C elegans,

Professor Gems is contributing a great deal to our understanding

of what the principles of ageing really are.

And once we know that,

things are going to get very interesting in this field.

Next time on Bang Goes The Theory,

flu - is it a case of winter sniffles

or a full-blown killer virus?

And, meanwhile, if you fancy working in ageing research,

check out our careers guide at bbc.co.uk/bang.

And to take part in an open debate of ageing and ageism,

follow the links through to the Open University website

and join the discussion.