An Interview with Eric Verdin of the Buck Institute for Research on Aging

Eric Verdin is the present CEO of the Buck Institute for Research on Aging. From my perspective most of the research programs carried out there, with the notable exception of matters involving cellular senescence, is fairly distant from the SENS rejuvenation research we'd like to see prosper. The Buck Institute as a whole reflects the broader research community focus on greater understanding of how aging progresses at the detail level, absent intervention, and on the development of ways to modestly slow the accumulation of damage, such as calorie restriction mimetic drugs.

Thus even among those researchers interested in treating aging as a medical condition, our community still needs to persuade many more of them to work on damage repair strategies capable in principle of producing rejuvenation in the old, rather than tinkering with metabolism to merely slow down the rate at which damage accrues. The hope is that as SENS approaches such as senescent cell clearance show themselves to be far more reliable, as well as cheaper and faster to bring to the clinic, this will happen. Meanwhile we have the existence of numerous research centers of a size comparable to the Buck Institute, with ten times the annual budget of the SENS Research Foundation, working on comparatively little that can possible produce meaningful outcomes in aging in the near future.

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.

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

Something happened in the 1990s. There were three groups that did an experiment that was really unexplained. Those groups all identified unique mutations in laboratory species 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. 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. Today we're at a point where people are considering starting clinical trials. This is why there is so much excitement and interest.

The Buck Institute 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. 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.

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. 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 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.

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

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. 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.



"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."

Yes! Exactly this. The sooner people move away from radical messaging the better. I couldnt agree more.

Posted by: Steve Hill at July 3rd, 2017 7:57 AM

I read the article 2 days ago.
At least he mentioned rejuvenation, unfortunately in his mind it's something the next generation will work on.

That's the problem with a field being dominated by people in their 50s and 60s (presently), they just want to push whatever takes the shortest time to get to clinic because they have 5-10 years of work left in them.
I can't say I don't understand why that is, a basic drug trial can take as long as 15 years and with the ever changing regulations on gene and cell therapies... no wonder why none of these venerable scientists wants to touch rejuvenation.

We need more young scientists with good ideas capable of getting funding for startup companies. That's about the extent of it. No amount of advocacy can change this status quo in a hurry.

Posted by: Anonymoose at July 3rd, 2017 8:21 AM

"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."

Again the total nonsense of compression of morbidity. People aren't healthy and suddenly age 50 years in 5 years. Nothing in biology supports that possibility.

@Anonymoose Hey, Aubrey is in his 50s ;) (and I think Gary Hudson is in his 60s)

Posted by: Antonio at July 3rd, 2017 9:03 AM

Eh, at least Mr. Verdin does mention lifespan as a goal and does refute the myth that 120 is an insurmountable age limit.

Posted by: Spede at July 3rd, 2017 9:51 AM

@Anonymoose is one way to put money and power in the hands of young scientists and those who refuse to accept the current situation.

Posted by: Steve Hill at July 3rd, 2017 1:21 PM

I liked this interview a lot. The conversations being had at the cutting edge of aging research are so much bolder now that even 1-2 years ago. He's flat out saying that we will have some form of geroprotectors available relatively soon. He's also saying we don't have any lifespan limits and he acknowledges next-gen therapies as regenerative. None of this is new to us, however its paving the way for EVERYONE ELSE to learn about this, accept it and anticipate these therapies. This is a good opening move and it starts to get people thinking and engaged.

I'm not too worried about him not pushing regenerative technologies. That's going to happen sooner than later anyway. Aubrey is confident that we will have lab results in the next few years that are pretty much going to shut the Negative Nanceys up with hard solid evidence. The research that we saw back in December from the Salk institute being a good example.

The pendulum is swinging in our favor. Its up to us to ensure that people become less afraid and far more excited at the possibilities.

We as the community will be shaping a new paradigm of what human life can look like. We have to be the examples going forward and help define what these changes in our culture mean. We have to be the positive examples of how we will embrace our extended lives.

Geropotectors are not rejuvenation, but they will buy us healthy decades of life. That buys us precious time. If a geroprotector can get me to 90 instead of 70, 20 years is a lot of time to develop better tech. I view them as a stepping stone to LEV, and will still be a BOATLOAD better than what my grandparents and parents had. Once we can put a dent in aging, the rest will follow. No longer immutable, or inexorable, it will be shown as plastic, and that's all we need to light the fire.

We just need one solid win. Just one... and it will open up doors far beyond aging.

Posted by: mborbely at July 4th, 2017 10:32 AM

"Geropotectors are not rejuvenation, but they will buy us healthy decades of life."

What is the basis for that?

Posted by: Antonio at July 4th, 2017 10:48 AM

@Antonio: Indeed. My primary complaint about the whole drugs to tinker with metabolism thing is precisely that the evidence suggests it will have minimal benefits. The cost of getting anywhere, is meanwhile enormous. Reliable minimal benefits for free, as is the case for the practice of exercise and calorie restriction, is a good thing and not to be turned down. But if throwing billions of dollars at the problem, pick a path with a better expectation value.

Posted by: Reason at July 4th, 2017 12:11 PM

@ Antonio

Based on the data we have on Metformin alone. Agreed, we should be spending bucks on rejuvenation, no contest, we will certainly get more bang for the buck out of that. However, by the same logic of Aubrey's LEV paper, geroprotectors like Metformin and various rapalogs will keep us in a disease-free state longer. We may only get a 3-5 year life extension out of them true, however we have to keep in mind that for many of us this is a marathon, not a sprint. If metformin can prevent you from being taken out of the game by a cancer say in your 50's and 60's, you've just increased your chance of making it to SENS 1.0. The whole idea of these drugs is to increase healthspan. Just by delaying those diseases even by a few years will allow many who would have died without them a shot at SENS.

We are changing the very definition of what it means to be human. We have had to build our current society to deal with aging and death at every level. It wont change overnight, but once we start making a dent in aging, it WILL change and I believe it will change quickly.

I'm in my 40's now like Reason. But my father was taken out by a cancer at 56. I'm in this for the long haul and a geroprotector might keep me around until we get SENS 1.0. Its certainly more than my father had.

Posted by: Mark Borbely at July 4th, 2017 1:04 PM

"Based on the data we have on Metformin alone."

What data? AFAIK, there is no data on metformin's effect on human lifespan.

"However, by the same logic of Aubrey's LEV paper, geroprotectors like Metformin and various rapalogs will keep us in a disease-free state longer."

No, the logic is very different. Geroprotectors slow down the accumulation of damage and SENS removes or makes harmless the damage. And the studies in different species show that geroprotectors effect is inversely proportional to natural lifespan.

"We may only get a 3-5 year life extension out of them"

One of the best treatments in mice (calorie restriction) gives them ~40% life extension, but it's barely measurable in rhesus monkeys. Same story for GHRKO mice (the current record holder) and human dwarfism. Thus it seems highly dubious to me that for example rapalogs will have a measurable effect on humans or an effect comparable to current life extension due to the progress of medicine (around 2 years per decade for people in their 40s).

Posted by: Antonio at July 4th, 2017 2:25 PM

Also, keep in mind that geroprotectors are given to animals from birth. They will have even less effect when used from middle age.

Posted by: Antonio at July 4th, 2017 2:37 PM

Fair enough, but Antonio... say in the next 5 years we get some geroprotectors on the market. Would you take them if proven safe and somewhat effective? Say is delays ill health for a while. Or would you forgo the whole exercise as a waste of time?

Posted by: mborbely at July 4th, 2017 3:43 PM

What is a waste is the billions that will be spent on developing it.

Would I buy it? No, I would spent the money in fundraising damage repair approaches.

Posted by: Antonio at July 4th, 2017 4:53 PM

If the data shows it works then it works. It would be foolish not to use something that works but YMMV

Posted by: Steve Hill at July 7th, 2017 3:57 AM
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