How Aging Research Is Changing Our Lives

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Biologist Eric Verdin considers aging a disease.

His research group famously discovered several enzymes,
including sirtuins, that play an important role in how our mitochondria—the
powerhouses of our cells—age. His studies in mice have shown that the stress
caused by calorie restriction activates sirtuins, increasing mitochondrial
activity and slowing aging. In other words, in the lab, calorie restriction in
mice allows them to live longer. His work has inspired many mitochondrial
hacks—diets, supplements, and episodic fasting plans—but there is not yet
evidence that these findings translate to humans.

If you hear the word immortality, just run.

Last year, Verdin was appointed President and Chief
Executive Officer of the Buck Institute for Research on Aging,
the largest independent research institute devoted to aging research. The
Buck, founded in 1999 by Marin County philanthropists Leonard and
Beryl Hamilton Buck, includes more than 250 researchers working across
disciplines to slow aging. Verdin, originally trained as a physician in his
native Belgium, is eager to translate findings from the lab work done over the
past 20 years in worms and mice to humans. “Aging without illness is our
overarching goal!” he wrote when he began at the Buck.

In a recent Nautilus interview, Verdin was optimistic about
the future. He thinks we’ll continue to live longer and age better. But to live
better longer, he says, requires research but also rethinking doctors’ visits.

Why is there so much energy and excitement surrounding
aging research right now?

Something happened in the ’90s. There were three groups
that did an experiment that was really unexplained. Those groups, Tom
Johnson, at the University of Colorado, Boulder, he actually was the first
one; Lenny Guarente [at MIT]; and Sue [Cynthia] Kenyon who was at the University
of California, San Francisco, all identified unique mutations that could
actually increase lifespan. At that time, it was a quite astute observation
in the way they completely turned upside down our conception of what aging
was.

The whole idea of aging was sort of an entropy problem
where everything falls apart like your car rusting, but what these papers
showed is that you can make a single change in one whole organism like C.
elegans with a 100 million base pair [genome], and you can double its
lifespan. Caenorhabditis elegans is a worm that’s often used as a model
organism. That by itself was mindboggling for a lot of people and suggested
there might be pathways to regulate aging, and if there are pathways that
means there are proteins, and that means you can eventually develop drugs.

In the last 15 to 20 years, we’ve identified a whole
series of pathways that are really key in regulating the rate of aging. Out
of this came a discovery of several small molecules. The first demonstration
that a small molecule could increase lifespan was done by Gordon Lithgow, who
was at Buck Institute. Out of this came a whole series of discoveries.

Today we’re at a point where people are considering
starting clinical trials. This is why there is so much excitement and
interest.

You recently became the president and CEO of the Buck
Institute for Research on Aging, which focuses on research aimed at
increasing healthspan. What do you mean by healthspan?

The whole mission of the Buck is not only to increase
healthspan but also lifespan, but we don’t want to increase lifespan at the
expense of healthspan. Every decade over the last hundred years, lifespan has
increased by two years. That’s amazing because we’ve gone from an average
life expectancy in the 1900s, which was around 47, to 77 today.

Exercise is an incredible anti-aging medicine.

That’s an incredible achievement, but this extended
lifespan is not all rosy. We also have an epidemic of what we call the
chronic disease of aging. I’m sure you’ve heard about the whole series of
diseases: Alzheimer’s, Parkinson’s disease, macular degeneration,
osteoarthritis, heart attacks, strokes, some cancers. Right now, in the United
States and most of the western world, we have a population that continues to
age and live longer, but that’s not always associated with a really good
quality of life.

Can those incredible increases in lifespan continue? Is
there an upper limit?

There currently is an upper limit, and the upper limit
is probably around 115, 120. You have a very large number—100 billion
people to choose the number of people that have ever lived—and you have
only one who has made it through to 122, Jeanne Calment. The second oldest
was 119. It does seem there is an upper limit. Some people have shown that
in the last hundred years, even though we have progressively increased the
average lifespan, the number of people who live above 115 has not
increased. That has to tell you that we might be reaching sort of a limit.
That’s already a pretty good limit. If we could all live to 110 healthy and
a disease in the last five years of life, I think most people would sign
for this.

But [this limit] does not anticipate future developments
in biology. I’ve been in experimental biology for about 30 years. What we’re
doing today is just amazing in comparison to what we were doing when I
started. You can’t imagine what we will be able to do in biology in 30, 50,
100 years. That’s why I don’t like the idea that there’s an absolute upper
limit that man will never live above 120.

Our mission for right now from my standpoint and from
the Institute’s standpoint is to continue that progressive gain of two years
[of life] every 10 years.

There’s a lot of Silicon-Valley buzz about longevity and
many startups working to develop immortality pills. What can be done to
ensure that research on healthspan and longevity is accessible to everyone?

First, if you hear the word immortality, just run. There
is no drug that can give you that. The people who talk about this do not know
what they’re talking about. It’s the same as the fountain of youth or the
holy grail and all of this. It makes for good movies, sometimes it makes for
good articles for people to read, but we are not any closer to immortality
than we were 1,000 years ago. It’s just nonsense from my perspective, and I
think we should really resist the I-word.

Aging is the major risk factor for all of these diseases.

I think [accessibility] is a problem not only for
anti-aging pills, but for all medicines. If you think about it, to develop a
safe medicine is extremely expensive, $1 billion for most drugs. The beauty
of our system is this whole patent system only lasts 15 years once you put a
drug on the market. It’s a little bit like statins, for example, that lowered
cholesterol. These drugs were very expensive at the beginning. Then they
became mass used, and now they’re generic, so they’re very cheap. I
understand the issue in terms of the potential cost of the medicine, but it
doesn’t mean we should not do it. We should keep moving forward.

One thing to realize about the inequality is that the
strongest risk factor for short lifespan is your socioeconomic status.
Poverty is the other big risk factor for short lifespan. As a society I
think, it’s not right to point at the drug companies and say, “Oh, they’re
making money.” I think we should probably make a decision as a society that
we should fight poverty harder. Then everyone would live longer.

What drives aging?

[At my talks], I show a picture of two Ford pickup trucks
from 1940. Just picture on the left that truck has been in the back of some
farmer’s field. It’s all rusted and lost its wheel and already sort of gone.
Picture the same truck on the right but in someone’s protection. The truck
has been completely maintained and renewed. It actually looks exactly like
the new one. The difference between these two trucks is not their age. They’re
exactly the same age; they were built in 1940. That’s what we call the chronological
age. The difference is their true age. In biology, it’s called the biological
age, how old your body is, really. Not how many years have you lived, but how
well maintained you are. If that’s the issue, if you take the truck analogy
you can understand the difference between the two trucks.

So how can we maintain our pickup trucks? How do we activate
these repair processes?

The thing that you and I can do today is nutrition and
exercise. Exercise is an incredible anti-aging medicine. It’s the best that
we have today and I suspect that we’ll have for a while. People who exercise
regularly live healthier and longer than people who don’t. Nutrition is also
really key, and this is an area where we learned about how much carbohydrates
you eat versus fat. Should you be fasting? Should you be doing episodic
fasting? All of this is being studied right now. Jack
LaLanne was one of the first gurus of exercise in the U.S. and
said, “Exercise is king. Nutrition is queen. Put them together, and you have
a kingdom.” I think it’s a beautiful saying—that’s what I tell everyone who
asks me, “What should I take?” I say don’t take anything, just don’t eat too
much and exercise regularly, and you will be fine.

Next, are the drugs that we are working on today. I would
say within the next five years we will have things coming into the market.

Last, is rejuvenation, therapies which are much more
science-fictiony. The idea that we will repair from the outside. Imagine that
we could grow heart cells in Petri dishes. You could take some of your cells
and then transform them into heart cells and repair the heart cells that you
have lost when you had a heart attack. These experiments are being done in
mice, and they work, but it’s still a big jump to put them in humans.

Why isn’t there more interest in aging research in the
larger biomedical community?

This [aging research] is a real paradigm shift in a way
that really changes much of what we think about these chronic diseases. I
think the biggest resistance is from medicine because medicine is organized
in a way that is not so compatible with what we’re doing. Medicine is
organized based on organs. You have a heart attack, you go see a cardiologist,
and he’s going to take care of your heart by deferring the risk for heart
attacks and controlling high blood pressure or high cholesterol. The
pharmaceutical industry developed all of these drugs to lower blood pressure
and to lower cholesterol. That’s fine. Heart disease is now going down, so
mission accomplished. The problem is you’re still at risk for Alzheimer’s
disease and for macular degeneration as well as arthritis and all of the
other ones.

What our field is proposing is that aging is the major
risk factor for all of these diseases. We should start targeting not
cholesterol and blood pressure. I mean, you still have to do this, but if you
start targeting the mechanism of aging, you will have a much more profound
effect against all of these diseases. That really is the promise of what we’re
doing. You would not go see a cardiologist; you would go see someone who
specializes in aging and who would optimize the rate at which you are aging.

It sounds like this would require a more holistic approach
for physicians. Would that change what a doctor’s appointment of the future
looks like?

I think so, and I think we will go there. I predict that—I
don’t know how fast, but—10 to 20 years down the line when these discoveries
have been established and the medicines exist, medicine will be more
preventative than curative. People talk about healthcare, but in essence what
we have right now is not healthcare. It’s sick care. Some people see their
physician when they’re well, but most people don’t because there’s not much
advice that they can give you other than not to smoke and to exercise and all
that. Physicians don’t really spend much time on prevention. What we’re
proposing is that when we target these mechanisms [of aging], we will be
working on prevention.

Do you consider your own mitochondria when you’re
deciding what to cook or order for dinner? Do you experiment with episodic
fasting yourself?

Yes, I do, but I have to be very careful about what I
say. I am an avid exerciser and I try to do episodic fasting. I don’t know
if it will make me live longer, but it certainly makes me feel better.

What would you be if you weren’t a scientist?

If I had any talent, I would have loved to be an electric
guitar player in a rock band!