The Sunday Times Magazine - UK (2022-04-10)

60 • The Sunday Times Magazine

T

he giant Galapagos tortoise

seems like an unlikely

ambassador for longevity. At

any age, you certainly wouldn’t

describe it as sprightly. But this

wrinkly, toothless giant, along with a few

other species including the (also very

wrinkly) naked mole rat, display what’s

called “negligible senescence”. Their risk

of death does not increase over time. For

us humans, the risk doubles every eight

years. For Galapagos tortoises, it stays at

an enviable 1-2 per cent throughout their

adult lives. As time ticks by, they don’t

become more frail or more prone to illness.

They experience no age-related decline

in fertility. As the fable suggests, they just

keep going until the end of the race.

How do these tortoises get old without

getting elderly? If we can understand that

— and harness it — we could change not

just the length of old age but also the quality

of it. We could live longer and healthier.

Most of us think of ageing as a natural,

inevitable part of being alive — but I believe

it is our greatest humanitarian challenge.

The top killers in the modern world are

diseases that disproportionately afflict the

elderly, such as cancer, heart disease and

stroke. Biologically, these are caused by the

ageing process, responsible for over two

thirds of deaths globally; more than 100,000

people every day. And these diseases don’t

kill you instantly — they are usually

accompanied by years of suffering, a loss of

independence and so on. Add in frailty,

hearing and sight loss, and the stress and

heartache for those caring for or losing their

loved ones, and the effects of ageing seem

like a contender for our largest problem.

There is good news. In the past decade

we have made huge strides in the lab in

both understanding and intervening in the

process. Scientists are finally in agreement

on the “hallmarks” of the ageing process.

These are the fundamental cellular and

molecular processes that

explain why we age badly

and the Galapagos

tortoise ages

very well indeed.

Between them,

these hallmarks

are responsible for

POOR GUT HEALTH

People who age well tend to have a diverse

population of microbiome or gut bugs.

Problematic microbes can take over in those who

don’t. We’ve all seen foods labelled “probiotics”

in the dairy aisle and these seek to introduce live

microorganisms into your guts when you eat or

drink them. There is another more direct way to

restore balance. Transplants of faecal matter

from younger to older fish and mice have been

shown to improve gut health (and longevity), and

similar transplants are already used to treat gut

infections in humans. Poo is purified, freeze-dried

and then inserted via colonoscopy, enema or by

swallowing a capsule. In time we might all be

popping tablets of freeze-dried faecal matter

to keep our guts in top condition.

IMMUNE SYSTEM MALFUNCTION

Our immune systems defend us from external

threats such as bacteria and viruses, and from

internal ones such as cells at risk of becoming

cancerous. We all have a crucial immune organ,

located in front of the heart, called the thymus,

and when it is firing on all cylinders it will create

new T cells — an essential part of our armoury

against viruses and precancerous cells. As we

age, our immune systems deteriorate and the

thymus becomes less effective. Scientists are

working on boosting our defences by rejuvenating

the thymus with drugs and growth hormones.

They are also experimenting with gene therapy

— tweaking our DNA by adding new copies of

genes that would encourage the thymus to

grow back to more youthful proportions.

everything from cancer and dementia to

wrinkles and grey hair. And that’s what is

getting scientists excited: rather than

designing bespoke treatments for hundreds

of types of cancer, dozens of drugs and

operations for heart disease, and a

cornucopia of skin creams for our cosmetic

woes, we could develop medicines that

tackle the root causes of ageing itself.

A cure for cancer would obviously be a

remarkable feat but it would add less than

three years to the average life expectancy.

Freed of your tumour, another nascent

age-related disease is likely to finish you

off a few years later. Instead, if we come up

with medicines to disrupt or prevent these

ageing hallmarks, we could increase our

“healthspan” — the amount of time we live

free from disease and disability. This would

have a more profound impact than picking

off the endpoints of ageing one at a time.

One of those hallmarks is the build-up

of aged “senescent” cells. These have long

been suspected to be responsible for a whole

range of age-related problems. They’re often

found loitering suspiciously in cancerous

tumours, failing hearts and declining brains.

But the most compelling evidence for their

culpability has come in the past ten years.

In 2018 scientists gave two-year-old mice

(equivalent to about 70 in human years) a

“senolytic” treatment — a cocktail of drugs

that removes their senescent cells but

leaves the rest of the cells intact. The

mice basically got biologically younger.

They lived a few months longer (perhaps

We w a nt to

live for ever

Dr Andrew Steele, an expert in the science of

ageing, explores how medical and technological

advances could give us longer, healthier lives

Four hallmarks of ageing — and what we can do to avoid them

Now I feel

months

younger