Show Notes
James Clement conducts research into anti-aging technologies. He has studied people over 110 years of age and has found a strong genetic connection to their super long lives. Yet, periodic environmental signals such as fasting and certain dietary supplements will prompt human cells to effectively cleanse themselves and recycle materials for energy. This causes cells, and thus bodies, to live longer. *This episode was originally released on September 25, 2019.*
TRANSCRIPT:
Intro: 0:01
Inventors and their inventions. Welcome to Radio Cade a podcast from the Cade Museum for Creativity and Invention in Gainesville, Florida. The museum is named after James Robert Cade, who invented Gatorade in 1965. My name is Richard Miles, we'll introduce you to inventors and the things that motivate them, we'll learn about their personal stories, how their inventions work and how their ideas get from the laboratory to the marketplace.
Richard Miles: 0:39
I'm going to live forever as a song from the musical fame, and if only that were true, but it turns out we can slow down some of the effects of aging and here to join me in my time machine thought capsule is, James Clemett, the CEO of Better Humans, a company that conducts research into longevity, disease prevention, and general human enhancement. Welcome to Radio Cade, James.
James Clemett: 1:00
Thank you, glad to be here.
Richard Miles: 1:01
So James, I'm not going to make you sing any songs from any hip musicals, probably to your relief, but I would like to have you start out by defining for us what anti-aging technologies are and what they actually do. And I'm going to ask my very first follow on question. Does this mean that we can live longer? Or does it mean we aren't afflicted by the normal conditions that apply to aging people?
James Clemett: 1:23
So the answer is yes to both of those things. We actually have longer living healthier people amongst us right now. I spent the last 10 years studying supercentenarians, and have met many women and men 106 , seven, eight years and older, all the way up to Morano in Italy who's 117 who are still cogent, living by themselves, often cooking their own food, and cleaning their own homes. One gentleman at 109 had just driven from the Tucson area to Denver in a sports car for his daughter's 80 something of birthday, a remarkable a feat for any elderly person, but at 109, amazing. So my initial quest was to figure out how these people live so long, how they do so in really great shape, and then to see what can we learn from that and apply to the rest of us who aren't so lucky.
Richard Miles: 2:17
So James, I'll just ask a kind of a nerdy social science question. It sounds like there are enough supercentenarians so people not just a hundred, but a hundred what?
James Clemett: 2:25
110.
Richard Miles: 2:26
Okay. Are there enough of that population to study and make valid conclusions that study this?
James Clemett: 2:32
That's sort of debatable. Okay. So my mentor, George Church, one of the top geneticists in the United States, he's at Harvard Medical School, he believes that you can discover rare phenotypes from even in of one . So a single person compared to everyone else's genetics, you can tease out what the differences might be. And certainly in a small family, brothers and sisters and mom and dad, et cetera, that haven't don't have a similar phenotype. Then you have an even better group to compare. So a mother and a son let's say who have protection against diabetes and can seemingly eat pure sugar and their blood sugar doesn't rise at all, and in that same family are two type two diabetics. Like that's a perfect scenario, tt's actually one that I'm currently studying. But uh, other people, Craig Venter being on the other side of that coin and I've had meetings with him about this issue believes you need thousands, maybe tens of thousands of subjects, and unfortunately, the number of people who at any one given time are documented supercentenarians in the world is about 60. And the turnover unfortunately is pretty fast. Um , so in five years there's basically a completely new group of 60 people, but that's still a small number when you're trying to tease out genetic variables, but we've actually been seeing some success in this. There are several scientists that spend their life focused on this and doing it near Barselli at Albert Einstein Medical School. Uh , Tom Pearls at Boston College are two of the leading experts in this field. And I based a lot of the work in my study on their past work.
Richard Miles: 4:11
So this is something I think a topic that is fascinating to most people, you know, looking at these 110 plus people, and you read an interview with someone like this and you read of one characteristic or one habit they have and go, aha, there we go, you know, they drank whiskey every morning or such and such. How much of when you interview, you study these people, how much do you take into account their sort of environmental habits versus their genetic makeup?
James Clemett: 4:34
Well, I came into this from the genetic side. So I had been on the board of directors of one of the first direct to consumer genetic testing companies, co-founded by George Church. George is a genetics professor, so we got together to start this study back in 2010, specifically, to look at the genetics. And even at that time, researchers from Europe had pretty much said that when it comes to supercentenarians, their ability to share this genetic information with family members, such as siblings, was 17 times higher than non-supercentenarians. So for example, a change in the genes that increase your chances of breast cancer, for example, is just a small order of magnitude, so it's maybe a 30% increase. Here, we're talking about a 1700 times increase percent increase. So 17 times greater chance of being a centenarian, if you have a close relative, who's a supercentenarian. So it's an amazing genetic advantage and we wanted to specifically focus on that. However, more relevant to your point is, in meeting the approximately 60 people of this age group that I did over a multiyear period. I can tell you that they come from Southern States, African-Americans whose parents were slaves. They come from recent Jewish immigrants, came to America, fleeing the Holocaust and Nazi Germany and became 110 year olds here. And I don't think that it is an environmental issue. We've tried to talk to them about their diets, not just at 110, but what do they recall eating when they were growing up, et cetera, and of course these people born at the turn of the century between the 18 hundreds and the 19 hundreds, they weren't eating McDonald's and other fast foods, they didn't have the luxury of these fantastically stocked grocery stores. So primarily they were doing what my grandparents did. I grew up on a farm and my grandparents lived right across the street from us and had a huge garden that they not only lived from in the summer, but then they canned all the vegetables for the winter and they had their own livestock. So they took that to a shop and had it butchered. And that's what they ate from as well. This is the same thing you see in both blue zones and with these supercentenarians while they were growing up is that they ate very natural foods.
Richard Miles: 7:00
If I understand correctly, your research has identified what's going on at the cellular level and that relationship to aging. If you could walk me through a little bit, what you found dealing with inflammation with zombie cells, what do you think you've found is going on at the cellular level with regard to aging or coming up with therapeutic anti-aging medicines? For instance.
James Clemett: 7:20
One of the things I did around 2013, I spent a year just looking at metabolism and how it's tied into calorie restriction, the ketogenic diet, fasting, et cetera, and about 500 papers into that, I started connecting dots. And the dots all seem to lead to an intracellular pathway called M-TOUR. It's a relatively new discovery from the 1970s based on bacterium that was found in the soil at Easter Island. And basically this complex that's inside all of our somatic cells. So every cell that has a nucleus tells us whether the conditions are right environmental conditions for that cell to go through cell division and to produce proteins. And so, if any of these environmental conditions don't meet the case, it stops that process and goes into recycling it's existing proteins and organelles on pretty much a dysfunctional basis, meaning it will take misfolded proteins and high R O S reactive oxygen species producing mitochondria. Those are the bad mitochondria that are producing a lot of free radicals as they make the ATP that energizes the cell and through a process called autophagy. It will surround these with a membrane, bring them to the lysosome, which is filled with acid, and then dissolve these proteins and organelles back to their basic compounds to be recycled in the cell. So, it's a very conserved process that goes all the way back to bacterium to allow the cell to survive hardship like a drought, food scarcity, not enough oxygen in the environment, different environmental triggers. But in humans, it very much tells the cell when it's time to repair itself and when it's time to make more of itself. This is at the heart of almost every anti-aging intervention we know of, including a lots of nutraceuticals. So a mega three Glucosomine ECG T , which is the extract from green tea, curcumin, lots of these things, suppress inventory and turn on autophagy and like most things in life, you don't want it all one way or the other. So you can't say, gee, I've read all these things that say fasting is really beneficial. I'm just going to fast for the rest of my life. I'm not going to eat anything that should be really beneficial, right? So instead you have to cycle these things back and forth. And whether it's following how we evolved, which was there were droughts, there were winters, there were ice ages, all kinds of things which impeded our ability to supply ourselves with all the nutrients and oxygen and everything it needs. Humans we're constantly going back and forth between feast and famine on a daily basis even.
Richard Miles: 10:11
So stress, no stress, stress, no stress. And that's, yes , kind of what keeps the cell healthy, or at least keeps it from doing bad things.
James Clemett: 10:18
Well, it's more that organisms have evolved to utilize these challenges. So by getting rid of the misfolded proteins and dysfunctional organelles that are inside the cells, it actually turned out that the cells would live longer, and in better health and that's the organism as a whole would live longer. So, we interrupt that process at our own peril. And unfortunately, from about the mid 1800s on, we've made so many advancements in agriculture and industrial agriculture, producing food products, preserving them with refrigeration for example, being able to ship things all over the world, both because of shipping in airplanes, but also the logistics we have capable of now of just-in-time produce at any grocery store practically in the Western world. We basically find ourselves with no famine ever in the Western world here , foods that didn't even exist in human history or have been modified through human effort. So if you look at old photographs, even Renaissance paintings of fruit, they don't look much like our fruit now they're really small, they were not really that great tasting. This is one of the reasons for example, apples were made into cider. Nobody ate an apple before the genetics were changed by human.
Richard Miles: 11:36
47 different varieties right?
James Clemett: 11:38
Yes, yes. And they're filled with sugar and really delicious to eat. Unlike what was made in the 1700s, for example, and our founding fathers drank this low alcohol ale and cider, primarily because you didn't have clean water.
Richard Miles: 11:51
Right, right.
James Clemett: 11:52
And to those products, they get boiled and then fermented, and those two processes is very protective against bacteria and other funk that would contaminate water and was found in groundwater. But we forget all this history and we forget how humans evolved. And we look at this abundance that we have now is just being normal and thinking that we just snack all day sitting at our desks, getting up only maybe to go to lunch that we're not going to have any ill effects and I think this is one of the things I've seen from both studying the supercentenarians, looking at the people who live in the so-called blue zones or health oases and studying the intracellular mechanisms that I think are being triggered by those people who live in these areas and follow these different lifestyles that allows them to live so long and so healthy is that this inter autophagy coin, so to speak, with one on one side and one on the other is really one of the fundamental anti-aging principles that we know now.
Richard Miles: 12:50
One of my theories about how this has gotten worse is whenever you get a package at home, with too much candy you got like, I know what I'll do, I'll bring it to work. Right? And so I place these to work in DC, I would never eat candy at home, but my golly theres a bowl of snickers there, and every time you go get a cup of coffee, you're going to stop at least once and get a tootsie roll.
James Clemett: 13:06
Yeah. And if you're in a large office, I previously had a career as an international tax lawyer and a park Avenue firm. You can end up in a big enough organization that there's a birthday or two every day.
Richard Miles: 13:17
Oh sure every day yeah, every day.
James Clemett: 13:18
There's always cake there.
Richard Miles: 13:18
Yeah you never have to bring your lunch right, there is something. Um , James, let's talk a little bit about the business or the commercialization aspect of the technologies that you're working on. People like movie stars and celebrities have always been dabbling in anti-aging processes for a long time have had access to all the latest treatments, some of which are probably work and some are quacks, but you want to actually make some of these technologies more available to just regular folk , lower costs. What does that look like? You have a company already, or are there companies that are getting these things to market? And I presume they're what drugs? Or there's some sort of treatments that are reasonable costs and that will eventually become a mass market type of phenomenon.
James Clemett: 13:57
Your first point, anti-aging up until very recently has been mostly cosmetic. So it's been basically tricking the outside world based on your skin and your muscle tone and things like that, that you were still
Richard Miles: 14:09
A facelift ain't making you any younger, right?
James Clemett: 14:11
You are still exactly, but certainly in the last 10 years, and now five years, we've seen just an exponential increase in our knowledge regarding anti-aging therapies. Uh, I started studying in 2008 and 2009, looking at where I thought the most impact was going to be, and it was, and I still think in kind of a combination of two things, STEM cells and genetic therapy and my unfulfilled dream so far is to combine those two. So taking your autologist STEM cells, taking them out of your body, genetically improving them. So let's say you've got an allele, like I have for increased risk of diabetes. Let's change that and then expand and put those STEM cells back into you so that you now have better genetic code then you started off with. So that's where I'm ultimately headed in my own research, but there's lots of scientists now working in anti-aging. I've seen a tremendous change where I would talk to scientists and they would say, Oh, I'm totally on board with this, but I can't tell anyone. And I was actually at a scientist presentation at Harvard, I think it was five or six years ago when he said I just got tenure, and now I can tell this entire audience that my sole focus in life is slowing down aging. And he said, I had to wait till I got tenure to do that, but that's no longer the case. And now there's anti-aging companies, you've got Google with Calico, HLI, which is something Craig Venter is associated with Human Longevity, Inc. Set up by Brian Johnson , Ajax with Mike West, Unity Biotech, lots of companies that are all looking at anti-aging therapeutics that will directly intervene in some aspect of aging in order to reverse damage that's already been done or prevented from happening. And I'm very much involved in this, currently, doing human clinical trials in areas where it involves nutraceuticals or things that don't necessarily have commercial value. So better humans. The organization that I founded and operate through is a nonprofit and we're entirely subsidized by a small number of donors. We have a pretty good budget. It's worked up over the years. So I started off with a very small lab in Los Angeles. I moved to Gainesville and I've been building a much larger lab and we're hiring local PhDs and bringing in PhDs with various specialties from outside the U.S. And I'm particularly focused on taking anti-aging therapies that are not going to be commercialized because either they're based on information that can't be patented or they are involving already generic drugs and or nutraceuticals. So for example, the Mayo clinic researcher Jim's Kirkland came up with a combination of drugs, one a chemotherapy adjunct called it's hot nib and another, a nutraceutical called Quercitin, which working together do a great job of killing off these senescent zombie cells. So these are cells that are stopped in their life cycle process. So instead of replicating, they go into this senescent or acquiescent cycle where they no longer replicate and they become dysfunctional and they actually produce pro-inflammatory cytokines. So those are proteins that basically tell cells and their near environment, I have some sort of problem you should send over immune cells and either get rid of me or send other anti-inflammatories. And if I'm being challenged by a virus or a bacteria, kill them off, but these are cells that probably haven't been attacked by a virus or a bacteria, but for other reasons, usually genetic damage just haven't been able to complete their normal cell cycle. And they get stuck in this for a really long period of time. And as they build up and it's believed that elderly people might have as much as 10 or 12% of their entire bodily cells are senescent. And these are producing these pro-inflammatory cytokines. You end up with individuals with very high levels of what's called chronic systemic inflammation. And their body is constantly in a fight or flight situation where they're trying to deal with an invader that doesn't exist. And so their organs receive all these pro-inflammatory proteins and basically stopped functioning as well. So there's drugs that kill off these cells, right? And your body restores new healthy cells in their place. So it's at least theoretically a really great therapy. The Mayo clinic was the first to highlight this and to say that they believed that it would work for certain pathologies like, osteoarthritis and pulmonary fibrosis. I had talked to the researcher at a conference to find out when they were gonna launch a clinical trial and he wasn't sure. So I decided to get an IRB. That's a institutional Review Board. They basically look at clinical trials and determine whether or not this is ethical in terms of the risk versus the potential benefit to medicine. And I got approval for a protocol to treat people with, inaudible and inaudible is a generic drug, persantine is an over the counter and nutraceutical you can buy, and we did a year long study giving 30 patients who had osteoarthritis and two who had pulmonary fibrosis in addition to osteoarthritis, these compounds only three times and saw absolutely amazing results.
Richard Miles: 19:25
So we're talking about, in one case, a generic drug that's already available and an over the counter, what was the second component?
James Clemett: 19:30
Nutraceutical.
Richard Miles: 19:30
Nutraceutical. Which is basically a supplement from either the plant or animal.
James Clemett: 19:36
Correct . It's a flavonoid, which comes from plants.
Richard Miles: 19:38
Okay. So that sounds very promising. I've already decided we're going to schedule our followup podcast 55 years from now when I will just have made it as a supercentenarians, and we'll see how this goes. James, in the time remaining, I'd like to ask you a little bit about yourself from listening to you talk, it sounds like you've been a scientist your entire career, but that's in fact not true. You did hint already that you're international tax lawyer, and then before that you actually started out in politics, right. Or a version of politics, let's go back before pre-professional you were from Missouri or were you raised on a farm or where were you raised?
James Clemett: 20:11
I was raised on a farm, my parents themselves were not farmers, but they built a house on my grandparents farm and my dad was an electrician, my mom was a nurse. I have one sister a year older than I am. I was born in 55, and so, I recall seeing John at Kennedy's, who we choose to go to the moon speech, for me, the entire Gemini, Mercury, Apollo missions were just meant for a kid.
Richard Miles: 20:36
Right.
James Clemett: 20:36
I was just absolutely infatuated with rocketry and space and astronomy and all this stuff. In high school, I was torn between opposition to the Vietnam war politically, and I would say most of my high school teachers who were luckily fairly young and liberal, versus my interest in science, and so I ended up going to college to study both of those. The science in the field of psychology through neurophysiology, and I was really lucky and I got an internship with a neurophysiologist at a nearby medical school and got published in science as a coauthor on a paper when I was a junior in college, which is a really big deal and I was very fortunate for that. But my other major was political science, and I helped politicians, mostly Democrats in Missouri get office. I ended up immediately after college working for the president pro-term of the Missouri Senate, helping him prepare for a gubernatorial election, and in that process decided I would go to law school. Again, really fortunate to get accepted to University of California Hastings Law School. I went there and pretty much right away was dissuaded by people who had sort of gone the route I'd looked at of international government as a career choice. Those who had done that basically talked me out of it. So I ended up becoming an international business and tax lawyer getting a job in Hawaii and helping mostly Asians from Japan and Hong Kong, which was still British at that time, invest in the United States and then went to NYU, got an advanced law degree in international tax planning, ended up working in New York City for a few more years, and then just decided to become a business person, and I sort of took my love of molecular biology and became a brew master opened up a brew pub at a college campus.
Richard Miles: 22:24
Bullet proof logics.
James Clemett: 22:26
Uh , yeah, I went from one bar to another and then just followed many entrepreneurial interests. But when I was turning 50, my parents were turning seventies. My dad had had open heart surgery and I was really starting to comprehend what aging was going to do to them, and decided that rather than being a dilettante and just standing by the sidelines and reading other people's books and taking their advice, I would get into the field myself .
Richard Miles: 22:52
That's amazing career arc. I got to say, James, I just want to know who's going to play you in the movie. Right? You trained as a scientist, you went into politics, you became a lawyer, and then back into science, and in nature where people are starting to think about retiring, you're plunging back into a pretty challenging field. I mean, this is not just some hobby, right?
James Clemett: 23:09
That's right. In the past 10 years, I've read over 18,000 scientific papers. And , um , I feel like I've made up for the fact that I didn't specialize in college, in biology, that I didn't become a doctor or a PhD. And I spend most of my time going back and forth between reading new papers , talking to other scientists and thinking about my own experiments and where we'll go from there. So the , the purpose of the lab is to basically back up some of the clinical trial work that we're doing with being able to use a mass spectrometer, to analyze proteins in people's blood, to do gene expression and DNA sequencing in our lab as well. So I'm really pleased that I have this ability. I absolutely love what I'm doing, I wake up every day, really excited to do one more thing, to try and slow down aging, and I kind of use my now nearly 90 year old parents as my inspiration and sort of guidance that we need this because I see so many people in their seventies and eighties that are suffering. And I recall meeting these hundred and nine, hundred and ten, year old people, they were doing just great.
Richard Miles: 24:13
Well I would think that's inspiration itself right? For you to say, hey mom, dad, you got to live another 20 years for even making it to my study. Right?
James Clemett: 24:19
Right. Absolutely. And I think there's something referred to by Aubrey DeGrey as longevity, escape velocity, and it basically means that as science provides us with better and better understanding, we will develop therapies that will just give you like one more year's worth or two more years worth of healthy lifespan, and I think in the very near future, we're going to get to the point where this happens more quickly than one year,
Richard Miles: 24:44
Right.
James Clemett: 24:44
So that we actually gain life span as time goes by, instead of it decreases as we age.
Richard Miles: 24:51
James, one final question, if you could go back and talk to your 21 or 22 year old self coming out of college, and you've got these two distinctly different interests, what do you wish you knew then that you know now, anything?
James Clemett: 25:03
So I'm a big sci-fi fan, and this idea of going back and telling yourself something never seems to work out in those stories. I think I would have preferred a lifetime in science rather than other areas. I'm basically a humanist at heart. So I deeply care about human beings and their ability to act. At the time, I thought politics was my way to help society and humans, but I think I'm more personally predisposed to figuring things out and that science is a perfect fit for me.
Richard Miles: 25:35
James has been fascinating interview and I've already got the studio booked for a 2074 for our followup interview to talk about.
James Clemett: 25:43
I hope we're both here too to do that.
Richard Miles: 25:44
Exactly, but thank you very much for joining me today on Radio Cade.
James Clemett: 25:48
Thanks very much.
Richard Miles: 25:48
I am Richard Miles.
Outro: 25:49
Radio Cade, would like to thank the following people for their help and support Liz Jist of the Cade Museum for coordinating inventor interviews . Bob McPeak of Heartwood Soundstage in downtown Gainesville, Florida for recording, editing and production of the podcast and music theme. Tracy Collins for the composition and performance of the Radio Cade theme song, featuring violinist, Jacob Lawson and special thanks to the Cade Museum for Creativity and Invention located in Gainesville, Florida.
