Episode 29
How Much Control Do We Really Have Over Our Health? Spermidine, Autophagy and Patient Empowerment
At 39, Leslie Kenny was diagnosed with rheumatoid arthritis and lupus and says she was told she had around five years to live. More than two decades later, she is in long-term remission and has turned that experience into a mission: helping patients become better informed, more involved and more confident in decisions about their own health.
In this episode, Leslie Kenny, founder of Oxford Healthspan and co-founder of the Oxford Longevity Project, joins Daphna Stern to tell the story of how she challenged her original prognosis, found intravenous immunoglobulin (IVIG) through her own research, changed her diet and ultimately reached remission.
But her story also raises a much bigger question: where should patient empowerment end and medical expertise begin?
The conversation then turns to spermidine, a naturally occurring compound found in the body and in foods that has attracted growing interest for its relationship with autophagy — the cellular recycling process that helps remove and reuse damaged cellular material. Leslie explains why she became convinced of its potential and why she believes natural compounds such as spermidine struggle to attract the research funding available to patentable drugs.
Daphna also pushes on the evidence. How much do we actually know about spermidine in humans? What can observational studies tell us — and what can they not? How does the evidence compare with interventions such as rapamycin? And when does an intriguing longevity molecule become something we can genuinely recommend?
The conversation expands beyond supplements into a broader discussion about personal responsibility for health, the exposome, the future of preventative medicine and what healthcare could look like if it focused not simply on extending life, but on helping people live well for longer — right through to the end.
Guest Bio
Leslie Kenny is the founder of Oxford Healthspan and co-founder of the Oxford Longevity Project. Diagnosed with rheumatoid arthritis and lupus at 39 and given a five-year prognosis, Kenny used patient research, dietary overhaul, and an experimental immunoglobulin therapy to reverse her condition into long-term remission. She trained at the Institute for Integrative Nutrition and now serves as Global Executive Ambassador for the Japan Autophagy Consortium. Through Oxford Healthspan, she develops food-derived spermidine and nettle-based nutraceuticals, and through the Oxford Longevity Project, she works alongside scientists including Sir Muir Gray, Sir Christopher Ball, Dr Paul Chen, and Emeritus Professor Dennis Noble to advance patient-centred ageing research.
LinkedIn: https://www.linkedin.com/in/leslie-kenny-oxford/
Timestamps
* 00:00 — Introduction to Leslie Kenny and her story
* 02:10 — IVF, autoimmune disease and the diagnosis that changed everything
* 04:30 — Questioning the original diagnosis and discovering a thyroid problem
* 08:15 — How patient research led Leslie to intravenous immunoglobulin (IVIG)
* 13:00 — Diet, elimination protocols and visualisation
* 17:40 — Reaching remission and turning personal experience into advocacy
* 21:50 — How to challenge your doctor without rejecting conventional medicine
* 25:30 — What spermidine is and why Leslie became interested in it
* 29:15 — Spermidine, the hallmarks of ageing and the comparison with rapamycin
* 34:00 — Why natural compounds can struggle for funding, patents and attention
* 38:20 — What the human evidence for spermidine actually tells us
* 43:10 — The funding problem in independent longevity research
* 45:30 — Oxford Healthspan and the Oxford Longevity Project
* 48:00 — How much control do we really have over our health and ageing?
* 52:00 — Rethinking hospitals, later life and what a good death looks like
* 56:30 — Rapid-fire questions
* 59:00 — Closing reflections
References & Further Reading
- Kenny, L. — founder, Oxford Healthspan
- Oxford Longevity Project (co-founded with Sir Muir Gray, Sir Christopher Ball, Dr. Paul Chen, Prof. Dennis Noble)
- Sears, B. — The Anti-Aging Zone
- Franceschi, C. — originator of the "inflammaging" concept
- Partridge, L., Madeo, F., Kennedy, B. — research on spermidine and the hallmarks of ageing
- Eisenberg, T., et al. — Grazer study on spermidine and human cell telomeres (2021)
Transcript
Foreign.
Speaker A:Longevity, the podcast that explores not just how we age, but how we can build a longer, healthier future for ourselves.
Speaker A:Leslie Kenney was 39 and trying to become a mother when she was diagnosed with rheumatoid arthritis and lupus and told she had about 55 years left to live.
Speaker A:Lesley is now 61.
Speaker A:Her autoimmune conditions have been in remission for years.
Speaker A:She has two children.
Speaker A:And much of her life is now devoted to a question that began with that diagnosis.
Speaker A:How much power do we really have to change the trajectory of our own health?
Speaker A:Lesley questioned what she was being told, searched for answers, and made enormous changes to her life.
Speaker A:But her experience raises a much bigger question.
Speaker A:How do you become an informed, empowered patient without crossing the line into believing that personal research can replace good medicine?
Speaker A:That question ultimately shaped the next chapter of Lesley's life.
Speaker A:She founded Oxford Healthspan Co founded the Oxford Longevity Project, bringing her into aging research and in particular, spermidine, a naturally occurring compound being studied for its effects on autophagy, the process through which our cells recycle damaged components.
Speaker A:Spermidine has attracted serious scientific attention, yet it is still far from an established longevity intervention.
Speaker A:We talk about why it caught Lesley's attention and what the human evidence actually shows and why, if the science is so promising, it has not become more widely accepted.
Speaker A:More broadly, we explore how much control we genuinely have over the way we age, where responsibility sits between the patient and the medical system, and what needs to change if medicine is going to focus more on keeping us healthy before we become ill. Hi, Lesley, thank you so much for joining me today on Beyond Longevity.
Speaker A:Before we talk about spermidine or Oxford Health Span, I want to start with the health problems that change the direction of your life.
Speaker B:Sure.
Speaker B:I guess the biggest thing was trying to get pregnant for a number of years and being faced at age 39 with a pretty stark choice, which was that my eggs were no longer viable and I would have to find a donor to give me eggs.
Speaker B:And having finally gotten my head around that, having my doctor tell me that I actually had rheumatoid arthritis and lupus and that there was no point going through with this round of IVF with the donor eggs, because even if I managed to get pregnant, something I had not managed to do in the many years before, I wouldn't live long enough to raise this child.
Speaker B:And they gave me five years, as you know, the time I would have left from the day of diagnosis, which was pretty stark.
Speaker A:Well, thank goodness you're still here.
Speaker A:And Your life story's changed quite dramatically.
Speaker A:Looking back now, what do you think your original doctors got wrong?
Speaker A:Was it the diagnosis, the prognosis, the treatment options, or sort of the certainty with which they presented them?
Speaker B:On the IVF side, I'm sure it was that they didn't look carefully enough at the thyroid gland.
Speaker B:And if they had, they would have realized that I had high thyroid antibodies as well.
Speaker B:That was undiagnosed at the time that the first two diagnoses came.
Speaker B:That wasn't diagnosed until years later when they realized there was no thyroid left.
Speaker B:Not making thyroid hormone with the doctor who told me that there was nothing I could do about the lupus and that I had five years left, I think the mistake was thinking that there was nothing a patient could do.
Speaker B:There's a saying that nature, patience and time are the three best physicians.
Speaker B:They mean patience as in having patience with time.
Speaker B:But I think it's actually patients themselves that are the ones who hold more answers than doctors give them credit for.
Speaker B:And I know you studied at the Institute for Integrative Nutrition and must value the role that nutrition has in our life and how much inflammaging we undergo.
Speaker B:But also, as a mother, you will know that if your kids don't get sleep, they don't function well the next day.
Speaker B:And, well, these things are true of adults, too.
Speaker B:There is a lot of common sense that we patients can actually apply.
Speaker B:And I think it was my second doctor's underestimation of what I was capable of doing myself and what I was willing to do, what lengths I was willing to go to, that really made the diagnosis so wrong.
Speaker A:Did you feel that they stopped looking for answers too soon?
Speaker B:They certainly didn't have the answers.
Speaker B:Did they stop?
Speaker B:Did they ever actually.
Speaker B:Look, I think that doctors today, the medical system is such that doctors are rewarded for properly diagnosing and prescribing.
Speaker B:Do they have the opportunity to or the luxury of time to go out there to search for answers for their patients?
Speaker B:I don't think they do.
Speaker B:That's left to research scientists.
Speaker B:And I know you interview a lot of them on your program, so you'll know there's a big difference between, say, a consulting physician and a principal investigator who's doing the research in the lab.
Speaker B:My doctor was simply telling me what the protocol was.
Speaker B:There was no protocol for lupus at that time.
Speaker B: It was: Speaker B:And giving me the odd straight because I sort of pushed her to give them to me since I was so desperate to go through with this round of IVF with donor eggs.
Speaker B:I was time pressed.
Speaker B:And I think that it's just the system does not allow doctors the luxury of time to get curious.
Speaker B:They don't allow doctors to, to walk alongside patients to investigate what the root cause of their illness is.
Speaker B:Nor do they allow them the time to walk alongside them as those patients try to make lifestyle changes.
Speaker B:And that is something which I believe patients now understand.
Speaker B:More and more patients are coming round to.
Speaker B:I have more power than I think.
Speaker A:Well, you certainly had more power than the doctors thought because you took it upon yourself to cure yourself, to help yourself get better.
Speaker A:Do you want to tell us a little bit about that?
Speaker B:Well, I was very lucky.
Speaker B:It wasn't that I cured myself.
Speaker B:It was really, I was able to rely on the work and experience of many other patients.
Speaker B:So I had learned this by going through IVF, that if you go to a patient forum with other IVF patients, they're very supportive.
Speaker B:And you often will get into a group of other women who are cycling.
Speaker B:We're all doing the same IVF transfer at the same time.
Speaker B:It's very supportive.
Speaker B:And so my first port of call as soon as I got the rheumatoid arthritis and lupus diagnoses was to go to these patient bulletin boards.
Speaker B:And on the rheumatoid arthritis bulletin boards, the patients told me, you know, I've been on these immune suppressing drugs that my doctor had prescribed for me too, just to stop my hands from becoming disfigured by the disease.
Speaker B:They said, you know, those immune suppressing drugs, they work for about 18 months and then they fail, and then you go into a new drug and then they fail and you go into a new drug.
Speaker B:And you at all times have to be so careful about not exposing yourself to germs because you're vulnerable if you're suppressing your immune system.
Speaker B:So I heard that on that patient bulletin board.
Speaker B: t had been done in Germany in: Speaker B:It is made up of.
Speaker B:They pulled antibodies from anywhere from 3 to 10,000 donors.
Speaker B:And that is done for people who can't produce antibodies.
Speaker B:But they noticed that actually in lupus patients given this, that it modulated their immune system.
Speaker B:And that was really the turning point for me was finding that therapy intravenous immunoglobulin or ivig.
Speaker B:And I immediately went to my doctor, very excited, hey, look what I found, isn't this great?
Speaker B:And the doctor said, actually, not great.
Speaker B:It's only 13 patients.
Speaker B:It's not statistically significant.
Speaker B:I can't give this to you.
Speaker B:So back to the patient bulletin boards.
Speaker B:I went and found a doctor through other patients who was willing to prescribe two rounds of this transfusion.
Speaker B:It was a cost of about US$12,000 each and took about four hours each one.
Speaker B:And when I finished with the second one, by the time I'd finished with a second transfusion, I had completely changed my lifestyle as well.
Speaker B:And I, under advice, stopped taking the immune suppressing drugs I had been prescribed for the rheumatoid arthritis.
Speaker B:And when I went back to my doctor for a routine checkup a few months later, she opened my file and said, well, look at that, you don't have lupus or ra.
Speaker B:And very excitedly, as any patient who hears something, some good news would be I said, excuse me.
Speaker B:And she said, all your labs have returned to normal.
Speaker B:And I said, well, that's amazing.
Speaker B:Do you want to know what I did?
Speaker B:And she said, no, that's okay.
Speaker B:And obviously it was now time for the next patient.
Speaker B:I know I'm not alone in having this kind of experience because other patients have told me it's happened to them too.
Speaker B:Again, the current sick care system does not afford our physicians the opportunity, the luxury of time to get curious.
Speaker B:But this is where scientific breakthroughs happen, is in curiosity.
Speaker B:And once we tell our doctors to stop getting curious, I think that's really terrible.
Speaker B:So it's up to us patients.
Speaker B:I don't think we can solve this problem of our physicians being time poor, especially as we all get more and more people are getting older, are presenting with chronic diseases and comorbidities.
Speaker B:We can't change that system.
Speaker B:These doctors have less and less time.
Speaker B:So it's going to be up to us patients to really advocate for ourselves, but also take some responsibility and really empower ourselves to make those lifestyle changes where we can.
Speaker A:Let's be clear here.
Speaker A:At that point, you're not a doctor or a scientist who's assessing evidence from a comfortable distance.
Speaker A:You were a patient facing a frightening prognosis and trying to work out whether there really were options.
Speaker A:Before you knew whether any of these choices you had, because I'm sure people suggested other things for you to try or do.
Speaker A:How did you decide what was credible enough for you to try?
Speaker A:Because the intervention you chose at the end was only done in a very small group.
Speaker B:As I mentioned, the patient chat rooms were really instrumental.
Speaker B:I relied heavily on them.
Speaker B: But in: Speaker B:And in that book, he talks about how autoimmune patients are aging prematurely, and it is through inflammaging at that point was a new term that Claudio Franceschi had coined.
Speaker B:Inflammaging was making them biologically older than their chronological years.
Speaker B:And what they needed to do was remove all the triggers to their immune system and add in things that were anti inflammatory.
Speaker B:So things like extra virgin olive oil, omega 3 fish oils, and a very clean plant based diet with some fish as well.
Speaker B:There was some animal protein, if you chose to.
Speaker B:And he also recommended that these patients get tested for allergens, which I did and could easily see that gluten, dairy, and eggs were a problem.
Speaker B:So I had to find new recipes to replace everything I'd eaten.
Speaker B:And that seems so daunting.
Speaker B:If somebody told you you've got to take these things out of your diet, you might think, oh, that's impossible.
Speaker B:But actually, I think people will be surprised by how many workarounds there are.
Speaker B:And I was pleasantly surprised.
Speaker B:And I've been able to really live gluten free and dairy free for years now, two decades, which is kind of incredible when I think about it.
Speaker B: h easier today than it was in: Speaker B:It was quite difficult then.
Speaker B:At the same time, I was a voracious reader and I looked for things that resonated with me.
Speaker B:So I looked at a book by Professor Gerald Epstein at Columbia University in New York City called Healing Visualizations.
Speaker B:And he had used these with cancer patients.
Speaker B:And I thought, well, I could create one myself.
Speaker B:And.
Speaker B:And I had initially used those for IVF to help with embryo transfer and implantation.
Speaker B:Now I was using them to try to calm my body down.
Speaker B:I also learned about the ACE test.
Speaker B:It's a kind of adolescent and childhood trauma test.
Speaker B:And I scored pretty badly on that and knew that I had some trauma therapy work to do involving writing letters to loved ones who'd already died, particularly my father, and just kind of releasing that because it appeared that there was some low level chronic inflammation from that.
Speaker B:As you can tell, everything from diet, dietary triggers to the immune system, to kind of chronic stress triggers, Whether it's trauma or just adding in things that are anti inflammatory, like extra virgin olive oil and healing visualizations, meditations.
Speaker B:I was definitely ready to embrace all of them if it could help me.
Speaker B:And that is where I do think doctors can underestimate the desire of some, not all, but some patients to really live and thrive.
Speaker B:And I think I'm an example of somebody who really wanted to make the changes.
Speaker A:Most definitely.
Speaker A:You did quite a few things at the same time.
Speaker A:As you said you had the ivig, you changed your diet, you controlled your stress levels and did a multitude of things at the same time.
Speaker A:So when your inflammatory markers and all that later normalized and you were told you were in remission.
Speaker A:Yeah, don't have it at all.
Speaker A:How did you make sense of what had actually made the difference?
Speaker A:Or was that not even relevant?
Speaker B:I was so focused on having a baby.
Speaker B:You're a mother, I'm a mother.
Speaker B:It's such a primal thing that once I was given the all clear, I was like, woohoo, saying goodbye to that, now where's the baby?
Speaker B:And I just went back to that goal.
Speaker B:So I didn't really think about it, honestly, until much later when I began to meet other patients.
Speaker B:So people you might meet at a party or you might hear about through friends would say, oh, their daughter, their sister was diagnosed with lupus or ra, and they didn't know what they could do.
Speaker B:They were put on methotrexate.
Speaker B:That kind of came after the immune suppressing drugs.
Speaker B:Methotrexate, for those who don't know, is a cancer therapy.
Speaker B:You're infused with this, but it's, it's not good for your eggs.
Speaker B:And in the same way that you're not supposed to get pregnant on roacutane because it's not good for your eggs, you're not supposed to get pregnant on methotrexate.
Speaker B:And so I'd listen to these stories about these other women and think this is really unfair because they're still going through the mill and can I help?
Speaker B:And I began to get more and more outraged that patients weren't being offered IVIG the way that I was.
Speaker B:Because I've mentioned that I did two rounds of IVIG at US$12,000 each.
Speaker B:The immune suppressing drugs I was given were about US$5,000 with my insurance, and that's a month per month.
Speaker B:And I've estimated that had I stayed on the immune suppressing drugs all this time, I would have spent, my insurance company would have spent over US$1.2 million.
Speaker B:So why not give them the $24,000 treatment, they're off of this chronic disease merry go round.
Speaker B:Because once you get one chronic disease, especially with autoimmune diseases, you will pick up others.
Speaker B:It becomes a collection.
Speaker B:And most of these people don't want to be collectors of autoimmune diseases.
Speaker B:Right.
Speaker B:It's not like collecting porcelain elephants or something.
Speaker B:And I was very lucky in that I was introduced to some scientists.
Speaker B:I moved from the United States to Oxford, England, where my husband was from, and met other parents and at the school Grand Gates, and through them learned about some really interesting research that was happening at the Kennedy Institute for Rheumatology at the University of Oxford.
Speaker B:So these were scientists who were looking at rheumatoid arthritis as well as other autoimmune conditions.
Speaker B:And they could see that this compound, which we all make when we're young and that is in all food and that our gut biome can make it, was modulating immune cells.
Speaker B:And initially this, these studies were done in mice, but have now been done in humans.
Speaker B:And it really struck a chord with me.
Speaker B:And I thought, this is amazing.
Speaker B:We need to bring this to market.
Speaker B:But when I asked the fellow from Oxford Science Enterprises who had, you know, in all fairness, introduced me to them, I said, look, I'll start a company and let's bring this to people.
Speaker B:This is exactly what I would have wished for.
Speaker B:Let's do this.
Speaker B:And he said, oh, no, we can't do this because this is a food and it can't be patented.
Speaker B:And we only invest in things that are patented.
Speaker B:And that made me even more outraged again because I also went to the Institute for Integrative Nutrition, like you and I know in the power of food, and had also witnessed it firsthand when I had removed the allergens from my diet.
Speaker B:I'm sure that was part of my remission.
Speaker B:And so I started then with bringing this food derived compound to market, this immune modulator.
Speaker B:And it's kind of become a labor of love, really.
Speaker B:And when times are difficult, I just, you know, I can dig really deep because anger at the injustice of it all, you know, really will fuel you.
Speaker B:Right.
Speaker B:I just don't want more people to go through what I went through, definitely.
Speaker A:And before we come to all these exciting things you've already touched upon, I just want to pull back a little bit.
Speaker A:And I just want to ask you, how do you encourage someone to say to their doctor, you know, or to themselves, I want a second opinion?
Speaker A:I want to understand my option.
Speaker A:I want to understand what's going on without them hearing my doctor's wrong.
Speaker A:I know better.
Speaker A:And in the worst case, stopping conventional treatment, that they may genuinely need to stay well or even to stay alive.
Speaker B:That's a very good point.
Speaker B:I think That I wouldn't suggest for somebody to come off their protocol, but that doesn't stop them getting curious and asking questions.
Speaker B: dical doctors in Japan in the: Speaker B:And I think maybe it's Western medicine, or maybe it's simply the power dynamic, sometimes medicine, it should be a partnership between the physician and the patient.
Speaker B:They both have knowledge.
Speaker B:The patient has lived knowledge and has many Data points from 24 living with this disease 24 hours a day, seven days a week.
Speaker B:The physician has knowledge as well, and together they are much more powerful.
Speaker B:It is not one plus one equals two, but if they can collaborate, it becomes one plus one equals three.
Speaker B:And hopefully a cure or a handle on this illness can be found.
Speaker B:And that's what I always say, is that if you can't get curious yourself as a patient with your physician, then perhaps it's time to find someone who really wants to collaborate with you and who will also listen to the things you say.
Speaker B:How many times do we open the newspaper and this happened just yesterday, a young woman, 34 years old.
Speaker B:So she's been telling her doctors for years about excruciating pain in her gut, and they keep dismissing it.
Speaker B:You're too young, it's not possible.
Speaker B:It turns out she has terminal cancer.
Speaker B:And I read these stories in the paper so frequently that I think we've got to start giving patients some credibility, some role to play in their own healing journey, and they must become true collaborators.
Speaker B:In the spirit of that.
Speaker B:If a patient says, I want to get curious, I want to get a second opinion, a physician should say, I welcome that.
Speaker B:That's great.
Speaker B:I don't have the time to explore this, but maybe another pair of eyes will be helpful.
Speaker B:So don't stop the protocol, but invite the curiosity from another party, an independent third party, to re examine all the facts and maybe they can connect the dots in a different way.
Speaker A:So you've already mentioned it without mentioning it, because that route that you took and moving to Oxford and meeting all these scientists by chance, dare I say, brought you to the research on spermidine and autophagy and immune aging and all these things, and spermidine very clearly convinced you in a way that many other promising longevity compounds did not.
Speaker A:What exactly is spermidine?
Speaker A:What did you see in spermidine research that made you think this is different?
Speaker A:This is worth acting on to your.
Speaker B:First question, Spermidine is something that it's such A terribly named compound named by Antonie van Leeuwenhoek, great biologist.
Speaker B:But why did he call it that?
Speaker B:Because he found it in samples of his own semen.
Speaker B:It is so important to survival of our species that it is found in semen, but it is also found in breast milk.
Speaker B:And we all make it.
Speaker B:Your grandmother makes it, your children make it.
Speaker B:There's nothing awkward or shameful about it, although people will find it a bit embarrassing to see say the name.
Speaker B:That's why I call it Primidine, because I just thought, I don't think my mother will ever be able to say this.
Speaker B:It just sounds so bad.
Speaker B:So it was definitely a molecule in need of a makeover.
Speaker B:But when we're young, we make it in our tissues.
Speaker B:We get it in vast quantities from our mother and mother's milk.
Speaker B:And the spermidine is there to help our cells proliferate quickly as babies.
Speaker B:We've got this massive brain, but we have a tiny body, and we need to grow quickly to support the weight of that brain.
Speaker B:The brain itself is also dividing rapidly and growing.
Speaker B:When we get older, our tissues stop producing it in such vast quantities, really around our late 20s.
Speaker B:Our gut biome is always capable of making spermidine, assuming we eat healthily and feed the happy, friendly bacteria that are capable of making it.
Speaker B:And we don't put rubbish in there, because what they eat is fiber.
Speaker B:This is why fiber is important and not, say, just sugar or ultra processed foods or emulsifiers or gums or gels or thickeners or E numbers.
Speaker B:Right?
Speaker B:And the other place that we get it is from plants.
Speaker B:So all plants make it.
Speaker B:And interestingly enough, in the plant kingdom, it is present in high quantities in the endosperm of the seed to help that seed grow quickly and survive.
Speaker B:So that's what spermidine is.
Speaker B:What convinced me of its merit was really its ability to activate something called autophagy, or cell renewal and recycling, as well as mitophagy, which is the renewal of the mitochondria inside the cell.
Speaker B:And the more that I looked past the research around reversing immune cell senescence, that's zombie cells, zombie immune cells.
Speaker B:I could see that it was inhibiting nine of the 12 hallmarks of aging.
Speaker B:And these are the pathways that scientists agree we age down.
Speaker B:So if we could slow nine of them and possibly a tenth, which would be senescence, then it just meant that the body would have a great opportunity to fight those other three hallmarks pretty handily.
Speaker B:So the only other compound I found that could Inhibit as many of the hallmarks.
Speaker B:Aspermidine was rapamycin.
Speaker B:But rapamycin is a drug given to suppress the immune systems of transplant patients who have been given donor organs.
Speaker B:And they've got to really strongly suppress the immune system so that their immune systems don't reject the donated organs.
Speaker B:As an autoimmune patient, I have injected myself with so many immune suppressants already.
Speaker B:I've had enough enbrilin, humira.
Speaker B:I don't want more.
Speaker B:So I didn't want to go down the rapamycin approach.
Speaker B:Not to mention the fact that many people I know, early biohackers who were experimenting were talking about open wounds inside their mouth, which.
Speaker B:That doesn't sound good.
Speaker B:The mouth is the start of the microbiome.
Speaker B:So what does the rest of the microbiome look like on rapamycin?
Speaker B:So that's the reason why spermidine caught my eye and it continues to intrigue me as a compound.
Speaker B:And not least because there's another hallmark of aging that scientists are talking about, the extracellular matrix.
Speaker B:And spermidine appears to have a role in that, positive role in that too.
Speaker A:So you've mentioned that spermidine is found within humans.
Speaker A:You can get it from food.
Speaker A:And I think this is the central question that I have about it all.
Speaker A:Spermidine is not French science.
Speaker A:Respected researchers are studying it, but it still has not become a science standard intervention across the longevity field.
Speaker A:If the evidence you know is as strong as you believe it is, why has spermidine, other than the unfortunate naming of it, not become one of the standard intervention in longevity?
Speaker B:Well, let's talk about the other interventions.
Speaker B:Maybe nicotinamide riboside, which did get started, the research got started earlier and I think that for nicotinamide riboside, the name of the company that manufactures that escapes me right now.
Speaker B:But out of Los Angeles they have now been invested in by Nestle.
Speaker B:Once a large company like Nestle begins to invest in a patented compound like nr, you then start to see big marketing dollars behind it.
Speaker B:And it's really about getting the word out.
Speaker B:Now I always say, again, as an IIN coach, you know, who started out looking at nutrition, I am a food first kind of person.
Speaker B:Please do not believe you can take my supplement and eat rubbish.
Speaker B:This does not give you a pass to eat McDonald's.
Speaker B:Sorry.
Speaker B:And you should, should get this from mushrooms, from legumes, from tofu first.
Speaker B:Well, none of that is sexy.
Speaker B:It's so much sexier to say, I've got this great pill and it's going to do everything for me and it is going to give me, it's a silver bullet and it's going to give me a pass.
Speaker B:I don't say that I also don't have patents to protect me from having lots of other people pile in here without a patent mode.
Speaker B:I think it's simply, it's unattractive to promote.
Speaker A:Can I just ask you about the 9 out of 12 hallmarks that spermidine touches, the hallmarks of aging?
Speaker A:When you say that, have those effects been shown in people or do some of them come from cell and animal studies?
Speaker A:Where have they been shown?
Speaker B:Some will be from animal studies and some will be in humans as well.
Speaker B:And for instance, I'm very careful not to say that spermidine inhibits cell senescence because we only know that it inhibits immune cell senescence and therefore I don't know about cells in other parts of the body and I don't claim that hallmark.
Speaker B:But this research was done by Professor Linda Partridge and Matias Fuente Alba at University College London and also by Brian Kennedy, who you probably, you probably know at National University of Singapore.
Speaker B:Just trying to see if I could find the paper that looks at this and from the Partridge, Fuente Alba and Kennedy paper.
Speaker B:And let's go to spermidine.
Speaker B:So for the initial six hallmarks of aging, which were eroded telomeres, epigenetic changes, impaired prevention, protein folding, dysfunctional mitochondria, stem cell dysfunction and impaired intracellular communication, according to them, spermidine inhibits the hallmark.
Speaker B:And then with three of those impaired protein folding, mitochondrial dysfunction and impaired intercellular communication.
Speaker B:The role in the aging phenotype or lifespan has also been shown experimentally, I would say with the eroded telomeres.
Speaker B:We've seen it in cells.
Speaker B:That was a German study, Wirt et al.
Speaker B: Which was done in: Speaker A:But that was all in vitro.
Speaker A:That was not in a person.
Speaker A:Right.
Speaker A:Just to be clear, you know, I always want to be very clear about what we factually know and also where we are at what stage of the research.
Speaker A:That's very important.
Speaker B:No, of course.
Speaker B:But what is interesting is that if you look at studies of what the long lived populations around the world are eating, there have been studies which have been done, I think it's Kiko, I don't have it right at my fingertips, which was done in Germany or Austria, showing that higher spermidine content in the diet was positively correlated with longer health span and lifespan.
Speaker B:Similar study was done in Japan as well.
Speaker B:And Also simply looking at the longevity blue zones.
Speaker B:Nicoya Peninsula in Costa Rica, Sardinia, Ikaria, Okinawa, Loma Linda.
Speaker B:Loma Linda.
Speaker B:They're, they only eat plants.
Speaker B:These Seventh Day Adventists don't eat meat, they're just eating lots of plants.
Speaker B:Therefore they will be getting a lot of spermidine in their diet.
Speaker B:The icarian Sardinians and populations in the Nicoya Peninsula in Costa Rica are having sheep's cheese and they're having plants as well.
Speaker B:And sheep's cheese does have some spermidine as well.
Speaker B:Cheese is a source of spermidine.
Speaker B:And the Okinawans have their, their fermented soybeans natto and they have a very small, special kind of extra slippery, extra smelly natto.
Speaker B:Very different from the rest of the Japanese on the mainland.
Speaker B:And so there is a, a link between this and diet and, and health as well.
Speaker A:I definitely see, you know, that a link can be made but I mean it is all anecdotal evidence.
Speaker B:I wouldn't say that about the Kekol research.
Speaker B:And I'm still, I'm just kind of looking to see if I can find it here.
Speaker B:I can send you that study afterwards.
Speaker A:Sure, we'll put it in the show notes.
Speaker A:No, no, no, absolutely.
Speaker A:Look, don't get me wrong, as I said, I always like to be very open and upfront and just because something is at the early stages of being tested that does not discredit it in any shape or form.
Speaker A:I just want to be clear about that.
Speaker A:You know, it's just because it is such a promising supplement.
Speaker A:I just want to know are you doing tests on humans anytime soon?
Speaker A:Are you planning it?
Speaker A:Is anybody else doing it?
Speaker A:Tell us about that.
Speaker B:Yes, yes and yes.
Speaker B:I have found the Kecal study.
Speaker B: or published in: Speaker B:The the study is called Higher Spermidine intake is linked to lower mortality.
Speaker B:A prospective population based study published in the American Journal of Clinical Clinical Nutrition.
Speaker B:So there is at least that one in terms of research.
Speaker B:So there are clinical trials that have already been conducted, a number of them in cognition and memory and that's where the minimum effective dose of 1mg per day has come from.
Speaker B:And that was using wheat germ derived spermidine.
Speaker B:So it is a food derived source and there have been follow on studies.
Speaker B:So at the University of Oxford by two of my scientific advisors, Professor Gada Al Saleh and Professor Katje Simon and she's also at the Charite in Berlin now and they published a paper earlier this year on food derived Spermidine from wheat germ at 6 milligrams and how it has improved vaccine response in the elderly.
Speaker B:Katja will be one of the first to say that vaccines in the elderly do not work well, not as well as they should because of this lack of spermidine and the inability of the immune cells to function properly in the presence of a vaccine.
Speaker B:There are some other studies that are ongoing.
Speaker B:We've certainly put in applications for, for use of spermidine with Parkinson's, with als, other illnesses that are what we call lysosomal storage disorders.
Speaker B:So lysosomes are just part of the autophagy mechanism.
Speaker B:It's like a cog in the machinery.
Speaker B:And if you don't have enough lysosomes, then the machinery of autophagy doesn't work.
Speaker B:And spermidine has been shown to increase lysosomal biogenesis, so increases the number of lysosomes.
Speaker B:So the question is really the funding because we can certainly provide the product to give to these individuals who are researching.
Speaker B:But the cost of a study, a clinical trial, is prohibitive and for small supplement manufacturer like me, that would be quite hard.
Speaker B:We have already done some research, it's not been published yet, but we're talking hundreds of thousands of pounds if you yourself conduct the research.
Speaker B:Now, of course there are a lot of organizations and I know you've had Do Not Age founder on and that's wonderful that you can then give your product to be used in a study.
Speaker B:That is by far the more cost effective way to participate in a trial.
Speaker B:And I think it's great done if the researchers have already got the grant to run that clinical trial.
Speaker B:But ethics alone can take a year and is very costly.
Speaker B:So that's just allowing you to enroll patients in your trial before you even get started.
Speaker A:Money is definitely a big barrier to a lot of research and all that.
Speaker A:I mean, even if you're a big company, it's prohibitive.
Speaker A:But it's very interesting that you mentioned Alan Grace from Do Not Age him, you, me, we are all sort of in a similar position in that we didn't originally start out, never mind in the longevity field, but not even in the medical field or, you know, in the science field.
Speaker A:And we all ended up here and sort of are quite big proponents now of that field.
Speaker A:How do you see your role in the longevity field?
Speaker B:Patient advocate, really.
Speaker B:It's really the patient empowerment work and I do that through my work with the Oxford Longevity Project.
Speaker B:I am the least qualified person there.
Speaker B:My board member, Sir Muir Gray, he's been writing preventive medicine textbooks for GPs and textbooks on how to slow the progression of Alzheimer's and dementia for decades.
Speaker B:Sir Christopher Ball, a longtime educator, also another board member, Dr. Paul Chen, an oncologist, you know, Ph.D. and medical doctor here at the University of Oxford and emeritus professor of cardiovascular physiology, Dennis Noble.
Speaker B:These people are doing the science.
Speaker B:All I do is say patients.
Speaker B:We have to do our role.
Speaker B:Dennis.
Speaker B:And Sir Muir and Dr. Paul Chen, they're looking at the research, right?
Speaker B:And we're always bringing scientists who have something new to say, whether it's Dr. Chris Van Tolkien, who's at UCL talking about Ultra processed foods and its impact on our health, which we brought him this year.
Speaker B:Shine a spotlight on him.
Speaker B:Or Professor Robin Choudhury, who's both a principal investigator and a clinician at the University of Oxford and talks about how important it is that we have good heart health in our teenage years.
Speaker B:I know you've got kids and that will serve them well in their later years.
Speaker B:Or Louise Newson, her work on hormones.
Speaker B:Or Professor Kiran Clark and her work on ketones and brain health.
Speaker B:These are people who, not Robin, but the others were what I call orphans who had something to say, had a body of work, but people were not always paying attention to what they were saying.
Speaker B:I think you know Chris's work with his ultra processed people.
Speaker B:That book was a New York Times bestseller.
Speaker B:This message is now finally getting through, but all I want to do is enable that.
Speaker B:So as a company, Oxford healthspan is the backstop.
Speaker B:We're the financial backstop.
Speaker B:We sponsor everything for the conferences and we try to shine a spotlight on those voices that might not necessarily get heard because there's ketone research as absolutely fascinating.
Speaker B:Do we have a lot of commercial activity in ketones?
Speaker B:Not really.
Speaker B:Not really.
Speaker B:But the research is very compelling.
Speaker B:It's very compelling.
Speaker B:Thank goodness for the, the Bouchy family and their foundation for really moving the needle on, say, the ketogenic diet and bipolar and schizophrenia patients.
Speaker B:So that's my role is really to shine a spotlight on the actual scientists and doctors who are making a difference for the benefit of patients.
Speaker A:So you've mentioned Oxford healthspan and the Oxford Longevity Project.
Speaker A:Just tell our listeners a little bit what each one exactly is and what each one does.
Speaker B:Oxford healthspan is a nutraceutical company and is really taking a food derived compounds of spermidine and nubilitin and commercializing those, just making them available and saying, look, we've done all the testing.
Speaker B:These are hand on heart, really food derived.
Speaker B:Here are the farmers who I visited to get these raw materials.
Speaker B:Most companies use synthetic.
Speaker B:They take a tiny amount of wheat germ, and then the rest of the capsule is full of synthetic spermidine.
Speaker B:That's fine, but we don't have safety or efficacy trials with synthetic yet.
Speaker B:That's what concerns me.
Speaker B:The Oxford Longevity Project, it was really born out of conversations with friends.
Speaker B:That would be Dennis Noble, Christopher Ball and Paul Chen during lockdown, where we felt, wouldn't it be great if we were told a little bit more than just remaining in place and banging pot lids together.
Speaker B:Is there not something more we can do?
Speaker B:Actually, patients do have more control than they think.
Speaker B:And our very first summit was around autophagy and immune health.
Speaker B: ught interviews with both the: Speaker B:He's a yeast guy.
Speaker B:So the mammalian work was done by Professor Tamatsu Yoshinori of Osaka University, and we work closely with them.
Speaker B:An adjunct to that, I'm also the global executive ambassador for the Japan Autophagy Consortium, where we're trying to get standards in place around supplements that say they activate autophagy so that consumers know.
Speaker B:Yes, if I buy this, it's actually happening and much easier to do in a country like Japan, which has.
Speaker B:They're at the forefront of a lot of regenerative medicine therapies like the Yamanaka factories, and they have already put into place legislation around how these therapies can be used by patients, which I think is great, but it's something I'd love to see in the rest of the world.
Speaker A:Let's talk a little bit about the longevity project.
Speaker A:In a recent report, they made quite a striking claim.
Speaker A:It says that individuals carry at least 80% of responsibility for ill health in old age.
Speaker A:What does that 80% mean in practice?
Speaker B:So that was a section authored by Sir Christopher Ball.
Speaker B:What it meant was that there are factors that are not genetically related, and these would be the obvious things that we have some control over, such as what we put into our mouths, how much movement we get, sleep, social connection, stress.
Speaker B:These are things that we could move a lever on.
Speaker B:Now, there's an important part of this that is your environment and the exposome, and that's not the genome, it's the exposome.
Speaker B:And Dr. Anant Joni spoke at our conference this year on deprivation.
Speaker B:Specifically, Dr. Chris Van Tolkien also talked a little bit about it.
Speaker B:But Anant Joni.
Speaker B:This is really his areas around deprivation.
Speaker B:So there's certain environmental factors we can't get away from as easily, such as air pollution or if we live in a food desert.
Speaker B:But then there are a lot of other things that we can do, such as moving or when it comes to social connection.
Speaker B:I don't know if you know this study, which was done about 10 years ago, showing that volunteering for a hundred hours a year, which is about two hours a week, actually improves your health outcomes.
Speaker B:Who knew that actually giving back and interacting with your community would actually be beneficial for you?
Speaker B:But it's things like this that we wanted to advocate for.
Speaker B:Again, letting people understand that it's not a genetic certainty.
Speaker B:Obviously, there are some genetic diseases.
Speaker B:There's some like Niemann Pick or Tay Sachs.
Speaker B:These are terrible diseases.
Speaker B:And.
Speaker B:And I hope that longevity science will find ways to cure them, perhaps with CAR T or other gene therapies.
Speaker B:But for the vast majority of us, the diseases of aging are lifestyle diseases, and we have more control over them than we think.
Speaker A:Definitely.
Speaker A:I mean, what you've said.
Speaker A:Pretty much everybody that's been on the podcast expressed a similar view.
Speaker A:The fact that we can contribute a lot to our.
Speaker A:Whatever you want to call it, health, longevity, all these things.
Speaker A:And while yes, some things do involve spending money, be it by buying supplements or having other interventions, a lot of it really is social contacts, moving and all that.
Speaker A:So there's undoubtedly something for it.
Speaker A:Now, just to sort of sum it up a little bit, you began this whole journey because you refused to accept that the future that you had been given by the doctors was inevitable.
Speaker A:After everything you've learned since, what do you now believe we genuinely can change about how we age?
Speaker A:And what do we still have to accept as we can't change it?
Speaker B:Well, first, I'd say just as we had to take on board the fact that neuroplasticity is possible, there is a.
Speaker B:A plasticity to our biological age.
Speaker B:And I think that people need to recognize that the number of candles on your birthday cake does not correlate positively with your biological age.
Speaker B:And I'm sort of one of these people who got a very low biological age in spite of the fact that I was told at 39 I should be dead by 44.
Speaker B:How is it possible I'm 61 now and have a biological age of 21 that doesn't.
Speaker B:Those don't seem to join up.
Speaker B:Right.
Speaker B:But this plasticity is there, and it means that we can improve the quality of our lives.
Speaker B:That's the healthspan part.
Speaker B:And I think that's what we all, all really want.
Speaker B:My mother's always said, your health is the most valuable thing in your life.
Speaker B:Without it, you can't appreciate life.
Speaker B:You can't enjoy time with your children.
Speaker B:It's the foundation for everything.
Speaker B:And so that is what I want people to come away with.
Speaker B:Every act that you do is either an investment in your future health or you're deducting from that future bank account.
Speaker B:Right.
Speaker B:So think of that, that you have more power than you think.
Speaker B:And then the other thing is, this may be controversial.
Speaker B:Maybe it's because I'm a little bit older, but death is going to come.
Speaker B:And I know there are people who have said it's the death of death.
Speaker B:I don't take that view.
Speaker B:Not yet.
Speaker B:I'm not saying that it could change later, but I think there is a good death.
Speaker B:And I think that we can prepare ourselves for the end of life in a way that honors the wonderful life that we've had, all the things we have seen, the history we have lived through, and that we've borne witness to, and all the loved ones whose lives we've also borne witness to, and vice versa.
Speaker B:And that is a celebration that's kind of my.
Speaker B:My controversial statement is that I believe, just like taxes, death will come for us.
Speaker A:I don't think it's so controversial, but, you know, here we go.
Speaker B:Yeah, well, in longevity circles, it can be.
Speaker A:We are a more realistic podcast here, I have to say.
Speaker B:Yeah.
Speaker B:So I think that I would like people to think about having a good death.
Speaker B:And my grandmother died with me, with.
Speaker B:With her only remaining living son, with her friends around her.
Speaker B:We bore witness to that passing, and it was a beautiful thing for her and for us.
Speaker B:And that, I think, would be also one of my life goals.
Speaker A:Yeah, very definitely.
Speaker A:And just to be sort of clear here, I think most of our listeners, when they hear longevity, they see that more as health span rather than lifespan.
Speaker B:That's good.
Speaker B:Not every podcast is like that.
Speaker A:No, no.
Speaker A:I think, you know, worth very much on that route.
Speaker A:But where do you see the longevity field heading in five to 10 years?
Speaker B:Well, one place I would really like to see changes made would be in our sick care system, in our hospital system.
Speaker B:Hospitals are a food desert.
Speaker B:You know, we tend to think of deprived inner cities as food deserts.
Speaker B:Well, guess what?
Speaker B:Our hospitals, our food deserts, too.
Speaker A:Too.
Speaker B:And that, I think, would be great to change.
Speaker B:I also think that our senior living accommodation is not up to scratch.
Speaker B:These should not be parking lots for People waiting for death.
Speaker B:These should be vibrant places where the workers, the staff members there are actively enabling the people who live there to, to get better.
Speaker A:Right.
Speaker B:And to be healthy.
Speaker B:I don't like when I hear that a senior care home, their exercise, their daily exercise consists of exercises from a seat where they're singing row, row your boat.
Speaker B:I think that's infantilizing some very wise people.
Speaker B:I think that we're going to see a big change and once wellness transforms that sector, I hope that should I ever need to go to one of these places and am not able to get older in place, that it's going to be a place where I'm going to get better and I'm going to learn more and I'm going to stay curious and engaged and hopefully that volunteering in the community piece will be there too.
Speaker B:Why can't we take those people in a care home and get them to help with volunteering?
Speaker A:Right.
Speaker B:It should not be a parking lot for deaf.
Speaker A:Definitely not.
Speaker A:But I want to push it even a bit further.
Speaker A:I don't think people that are going into these old age homes are even at a place where all they can do is sit in a chair and move their arms a little bit.
Speaker A:That should not even be the case.
Speaker A:They should get there being elderly and maybe needing help reading or doing stuff like that.
Speaker A:But they should be physically active.
Speaker A:And as we've discussed, 80% of it is lifestyle.
Speaker A:So hopefully our generation once, and obviously the people are even younger than us once we get to that stage, old age home sort of stage, maybe we don't even need that.
Speaker A:You know, we can live happily in our own homes.
Speaker A:And the idea is live healthy and happily be ill or impaired for two weeks and then die.
Speaker B:Exactly, exactly.
Speaker B:Compression of comorbidities.
Speaker B:I think that's right.
Speaker B:That's my goal.
Speaker B:And my colleague Sir Muir Gray always says that the moment you cannot get up, cannot sit down and get up from the toilet, that is the day you will be exiled to a nursing home.
Speaker B:So for anybody listening, that's the metric.
Speaker B:I know it might sound a bit coarse, but that is the reality.
Speaker A:Yeah.
Speaker A:And the reality is we should all be knowledgeable enough now to know to not let it get that far.
Speaker A:I think this is the main message.
Speaker A:Keep active, do these things so you know, it doesn't get that far.
Speaker A:I agree with you on that one.
Speaker A:So yeah, definitely some change needs to happen one way or the other.
Speaker B:Agree 100%.
Speaker A:Now, before we finish up, I always ask my guests five rapid fire questions.
Speaker A:What's the single best piece of advice you would give your younger self?
Speaker B:Give my younger self stay curious.
Speaker A:Name one habit everyone should adopt for a longer, healthier life.
Speaker B:10 Squats every every half hour.
Speaker A:If you weren't.
Speaker A:Well, that question doesn't really apply to you because you've had so many careers before.
Speaker A:But if you weren't in the longevity science right now, what career would you have chosen?
Speaker B:Oh, endocrinology.
Speaker A:What microdose habit, five minute routine or small daily action yields outsized longevity benefits?
Speaker B:Actually, I quite like astaxanthin.
Speaker B:You don't have to take a lot of it, but it confers UV benefits to your skin and you don't have to think about it too much.
Speaker A:What's the craziest longevity myth you've encountered?
Speaker A:And is there any truth to it?
Speaker B:The craziest longevity myth, it might be the death of death.
Speaker B:To be honest, I think that is the biggest myth that we have hit escape velocity and it is the death of death.
Speaker B:Right now, we're certainly at life extension, but the death of death.
Speaker B:No.
Speaker A:A hard no.
Speaker B:A hard no.
Speaker B:Yeah, yeah.
Speaker A:Not yet, not yet.
Speaker A:You know, you never know.
Speaker A:Science and biology is moving at a crazy pace.
Speaker A:So never say never.
Speaker A:But at this moment, I do agree with you.
Speaker A:It's a hard no.
Speaker B:Yeah, exactly.
Speaker A:Well, listen, Lesley, thank you so much for joining me on Beyond Longevity.
Speaker A:It was a pleasure talking to you.
Speaker A:And wow, what an inspirational story.
Speaker A:I mean, if you don't give hope to the masses, then I don't know who.
Speaker B:Well, thank you.
Speaker B:It's been a pleasure as well.
Speaker A:Lesley's story is extraordinary, but I think the most useful part of it is not the idea that everyone can reproduce her outcome.
Speaker A:It is that being a patient does not have to mean being passive.
Speaker A:There is an important balance here.
Speaker A:Asking questions, seeking second opinions, and taking responsibility for the things we can change is very different from rejecting conventional medicine or assuming that something that worked for one person will work for everyone.
Speaker A:Spermidine is also a fascinating part of Lesley's story.
Speaker A:There's some genuinely interesting science behind it, particularly around autophagy, and enough promising research to understand why Leslie became so interested in it.
Speaker A:The human evidence is still developing, but it is certainly a compound worth watching as that research progresses.
Speaker A:And perhaps at the broader point is simpler.
Speaker A:We spend a lot of time and longevity talking about new drugs, biomarkers and technologies.
Speaker A:But many of the biggest levers we have are already available to us.
Speaker A:How we eat, move, sleep, manage stress, and stay connected to other people.
Speaker A:The science will continue to move forward.
Speaker A:In the meantime, there is already a great deal we can do to give ourselves the best chance of living longer and more importantly, staying healthy while we do.
Speaker A:Thank you for joining me today on Beyond Longevity.
Speaker A:Please rate, subscribe and review.
