Dr Andrew Steele, author of Ageless (Photo: Tran Nguyen)

“To many people, who believe aging is a natural, inevitable side-effect of being alive, this
probably sounds like quite a strange thing to say,” says Steele. “But what really drew me
to this idea was a statistical realisation predominantly based on the graph of how your
risk of death changes depending on how old you are.”

Aging: the biggest risk factor of all

The statistics say that our risk of death doubles about every eight years, and the raw
numbers behind that shocked Steele, who, at 36 years old, has a risk of death of about
one in a thousand today.

“I quite like those odds,” he says. “But if I’m lucky enough to make it into my 90s, and
there’s no progress in medical technology in the intervening time, my risk of death in the
first few years of my 90s is going to be one in six, which is life and death at the roll of a
dice.”

Rather than simply accepting the fact of this approaching “wall of mortality”, Steele
considered the information through a physicist’s eyes.

“It was fascinating to think about what might be driving this shockingly synchronised
increase in the risk of all these different diseases, frailty, and all these different changes
that are happening our biology,” he says. “And, if we could understand what’s behind
that, could we do something about it?”

These questions led Steele to discover the research that has been going on in the
longevity field, and that indeed it is possible to “do something” about aging.

“This was around the time when the rapamycin experiments showed lifespan extension
in mice, so there was a lot of excitement around that,” he says. “And then the hallmarks
of aging paper came out a couple of years later, and there was a coalescence around
the idea of what aging actually is, which had been a huge mystery for a long time.

“So, on one hand we had aging – the world’s biggest humanitarian challenge, and on the
other we had the scientific tools to rise to that challenge. And so, I thought – this is the
field where I need to be.”

Spreading the word on longevity

To pursue his interest in aging, Steele switched focus to become a computational

biologist and spent the next decade or so building his knowledge and understanding of
the field. His decision to write Ageless came through a realisation that, while those
working in the longevity field are fully aware of the promise it holds, most people are
still blissfully unaware of the exciting progress being made.

“What I really wanted to show that this is not some sort of wacky sci-fi nonsense, which
is how I think a lot of people, including scientists, imagine the field of aging,” he says.
“They think it’s this inevitable, super-complicated process that we can’t possibly
intervene in or study in any useful way.”

While he wrote the book to help get the word out on aging science to everyone from the
public to policymakers, Steele was also surprised by how often he came across
scientists and doctors who knew nothing of the work going on in the aging field.

“It was incredible – someone could have a great PhD from a great university and literally
have never had a lecture on aging biology. It’s not in the textbooks. My wife is a doctor
and when I met her, I think she thought I was crazy talking about all this anti-aging stuff.
And yet, she is probably going to have to prescribe anti-aging medicines during her
career!”
Senolytics vs metformin
With his broad view of the aging field, does Steele have a view on which areas hold the
most promise for delivering a therapeutic that will show results in humans? While he
acknowledges that diabetes drug metformin may end up being the first, the potential he
sees in senolytics is far greater.

“Metformin is a pre-existing drug – it’s off patent, so it’s going to be super easy – if the
TAME trial works, we can start prescribing it essentially immediately,” he says.

“But the thing I’m most excited about in the near term is senolytics. They are going to
have a slightly longer path to market because they’re currently being trialled for specific
conditions, and there are a few more steps before we start handing them out to healthy
50-year-olds. We need to be really sure they’re safe, they’re doing what we think they’re
doing, and that they don’t have any long-term side effects.”

While metformin’s longevity benefits could be thought of as a “side-effect” of some

other biological processes, Steele feels that senolytics present a more compelling
proposition when it comes to targeting aging.

“I’m more excited about senolytics than am I about metformin because we’ve got a
really good idea of what they’re doing, why they’re doing it, and how they work,” he says.
“And I think that means they are going to be the first ‘true’ anti-aging medicine. Yes,
metformin could turn out to be important, and it could give people more healthy life, but
I think the effect will be smaller and less significant from a scientific and medical point
of view. I’m more excited by the idea of something that goes after one of the hallmarks
of aging.”

Be safe and be bold

Of course, to prove that age-targeting therapies are working, Steele acknowledges that
we need a way to conduct proper trials and to find ways to clearly measure changes in
our aging as a result of taking them. But he also feels that efforts to define aging
shouldn’t hamper our progress towards getting safe interventions approved.

“I think it’s important that we sort this out because, if we wait for certainty, then we’re
going to end up leaving a lot of healthy life on the table,” he says. “The point is going to
come where we’re pretty sure that some combination of measures of biological age is
meaningful, and therefore, it would be irresponsible of us to just ignore that fact.

“But the real challenge is, when do we consider these things safe? And this is a
question for scientists, regulators, politicians and the public to have a debate about.
Because I think it’d be a great shame if we spent 300 years doing the perfect set of
trials and discovered that we had the anti-aging drug all along.”

Can aging really be “cured”?

The ultimate goal, says Steele, should be to “cure aging” – a phrase that many in the
field are uncomfortable with.

“What I mean by curing aging is having a risk of death that doesn’t vary depending on
how long ago you were born,” he says. “A lot of scientists, even aging biologists, get a
little bit squeamish when you say that. But I really do think that should be the
fundamental aim of all medicine.”

Steele uses cancer as an example and says that most scientists working in that field
would agree they are working towards an end goal of curing cancer.

“I don’t see why aging should be any different,” he says. “At least the aspects of aging
that cause frailty and discomfort and distress and pain and disease and all these
horrible things we want to get rid of. I don’t see why our goal shouldn’t be to minimise
that human suffering as far as possible. And to me, that means curing aging.

“How possible is that going to be? I’m absolutely convinced it’s possible at some point.
There’s no law of biology that tells us we must age – we can look around the animal
kingdom and see animals that don’t age, they’re negligibly senescent, they have exactly
this risk of death that doesn’t vary depending on how long ago they were born. The real
question is, are we clever enough? Is our biotechnology advanced enough? And are we
going to get lucky enough that it’s going to happen in our generation?”