Professor Lorna Harries has spent more than two decades studying why cells age and what might be done about it. In this episode, she explains one of the most overlooked mechanisms in ageing biology, RNA splicing. When cells lose control of this process, they become stressed, dysfunctional and can tip into senescence, a state that contributes to ageing across almost every organ system.

She explains what senescent cells actually do, how the signals they release can spread damage from one tissue to another, and why calling them “zombie cells” does not come close to telling the full story. We talk about the possibility of intervening before cells reach an irreversible state, why targeting the biology of ageing itself may matter more than tackling diseases one at a time, and what meaningful rejuvenation should really look like.

Prof Lorna also discusses the challenge of turning lab science into therapies through her spin-out SENISCA, her work with L’Oréal, and why conditions such as IPF are an important place to begin. Along the way, she addresses the tougher questions too, including how longevity science moves from promise to treatment, where the field risks drifting into hype, and whether these advances will be available to the many or only the few.

Links:

http://www.senisca/

http://www.iscarna.com/

https://teamrna.wixsite.com/harrieslab

https://experts.exeter.ac.uk/1873-lorna-harries

Innovate UK ICURe Programme

https://iuk-business-connect.org.uk/programme/icure/

00:00 Podcast Intro Guest Setup

01:50 Meet Professor Harris Basics

02:16 DNA RNA Explained

03:38 RNA Splicing And Ageing

05:48 What Senescent Cells Do

07:38 Reversing Senescence Window

09:01 Fat Tissue And Faster Ageing

11:01 Splicing As Central Hallmark

12:11 Rejuvenation Discovery Story

13:52 From Lab To Spinout Company

16:41 Translating Science To Products

19:17 Therapy Targets IPF And Beyond

21:45 Why Translation Often Fails

23:19 Defining Real Rejuvenation

25:14 Avoiding Hype In Longevity

27:17 Who Is Lagging Behind

27:37 Regulatory Mindset Shift

28:47 Trials Built for Ageing

29:28 Scepticism and Overhype

31:25 Is Ageing a Disease

32:49 Policy and Demographic Timebomb

33:48 Advocacy and Communication

35:24 Personal Ageing Habits

36:24 Key Unasked Questions

39:15 Longevity for the Rich

41:43 Access via NHS and Patents

45:06 Rapid Fire and Myths

49:05 Closing Reflections

Foreign.

Welcome to Beyond Longevity, the podcast that explores not just how we age, but how we can build a longer, healthier future for ourselves. My guest today is Professor Lorna Harries, a professor of molecular genetics at the University of Exeter.

Professor Lorna's work focuses on on the biology of aging, cellular senescence and how discoveries in the lab may eventually lead to real interventions for age related diseases. We talk about how something as ominous sounding as RNA splicing could turn out to be one of the most important processes in aging biology.

As Professor Harries explains, when cells lose the ability to manage that process of RNA splicing properly, they become stre dysfunctional and can tip into senescence, one of the key drivers of aging. We talk about what senescence cells are actually doing inside the body, why they are much more than so called zombie cells.

We discuss whether some of this damage may be reversible and why it may make more sense to target the underlying biology of aging rather than keep treating diseases one by one.

We also get into the bigger what real rejuvenation would actually look like, where the field risks drifting into hype, how the science begins to move towards practical and real world application, and why this area of research could change far more than most people realize. Hi, Professor Lorna, thank you so much for joining me today on Beyond Longevity.

For people not knowing much about the topic that you are deeply involved in DNA, rna, before we get into the nitty gritty, tell us a little bit about yourself and, and then maybe also tell us what DNA and RNA really is.

Okay, so that's a big question. Yes. I'm Lorna Harries.

I am a professor of molecular genetics at the University of Exeter, and my team work at the intersection between sort of how and why we age and what we might be able to do about that in the future. So I've been in the academic arena for, gosh, a very long time now.

It's my 25th year in Exeter, and over the past sort of 20 years or so, we discovered a new mechanism by which cells age, which is changes in how and where your genes are expressed. So we work with a molecule called rna. All of the cells in your body have all the DNA they have.

So the genes are in the DNA, they have all the genes, but they're not all switched on at the same time in the same place. So that's why with actually what's quite a small number of different genes, we can make such an incredible array of different things.

And what makes, for example, a cell in your brain different from a cell in your heart. So DNA is basically the instructions, and when your gene is activated, it makes basically a copy of itself called an rna.

And that is a little bit like taking a photocopy of a recipe, for example, that allows us to switch particular genes on in particular places. And what we found as we get older is that we lose our ability to regulate this and to do this properly.

So genes get switched on when they shouldn't be switched on, and equally also can get switched off when they shouldn't.

Correct me if I'm wrong, but the faulty RNA processing is sort of part of why we age. Or is it more a sign that aging is already happening? How do we put the two together?

And as a little sort of add on, there is this thing called RNA splicing, which I think is part of it and in which you specialize. Can you just elaborate a little bit more on that?

Because most people would have heard of DNA and I'm sure some know what RNA is, but I think RNA splicing is still where you lose a lot of them.

Yeah, that'll be a new thing to a few people. So this, again, this comes back to different things being made in different places at different times.

We have about 15 to 16,000 genes in our genome, but we make about 200, 250,000 different things at different times in different places.

So the way we're able to do this, and it's one of the things that actually differentiates us from things like bacteria or yeast, which are pretty simple organisms, is the ability to make multiple things from one gene. So my favourite analogy here is a little bit like a recipe book. You have a recipe book that, let's say it makes cake.

With that same cake recipe, you can make either a victorious sponge or you can make a chocolate cake, depending on whether or not you put the chocolate in. So that's a little bit what RNA processing is. So it's the ability to take one set of instructions and jiggle them around to make different things.

What we discovered as we age, we lose the ability to do this.

So the genes that make the decisions as to what gets made at any one time start to become switched off as we get older, which means you lose your ability to basically change what the cell is making. And what that means for the cell is if the cell is unable to adapt to its environment, it will become stressed.

And when cells become stressed, they can enter a state called senescence, which is one of the things that we know is a driver of aging. So you asked me whether or not I Think that dysregulation, these processes, are cause of aging or just a passenger? I think it's actually.

It's definitely a cause, but it's also a way that we can measure at the biological aging level, what's going on in cells.

So you've mentioned senescent cells, cellular senescence, often called zombie cells. Can you just explain a little bit more what a senescent cell actually is doing differently to a healthy cell?

Yeah, senescence is a process that when cells divide and things occasionally might go wrong with them, We've evolved that these cells will occasionally reach this state called senescence, which basically turns them off. They send that chemical signals into the environment, which call the immune system to clear them.

As we age, our immune system becomes less efficient, and those cells start to accumulate. And pretty much all different types of cells, with very few exceptions, can actually become senescent.

And some sorts of senescence are actually important. So you. During sort of development as an embryo, Senescence is important for things like development of your hands and your fingers.

It can also be an important part of the sort of things like wound healing Sometimes can involve some of the same pathways as incinescence. But during the aging process, these cells start to accumulate at levels much beyond that that they should have, and they become dysregulated.

And the reason why this is a problem is they acquire a bunch of new features. So, you know, the cell will perhaps stop doing what it should do, and it'll acquire these new features.

It starts to look very different, to behave very differently. They stop growing, they stop dividing, but they remain alive.

They're very metabolically active, and they start to throw out all of these signals into their environments, which, in the absence of an effective and functional immune system, Just cause havoc.

These signals go out into the bloodstream, they go around the body, and they can actually provoke senescence in other cells and other systems, which is why the media call them zombie cells. But we know quite unequivocally now they are a really fundamental driver of not just cellular aging, but systemic aging.

Before a cell becomes fully senescent, Is there a point at which it's still reversible?

Yeah. So, I mean, that's the other thing to mention here, is there isn't just one type of senescent cell.

Cells can become senescent through a variety of pathways, but ultimately, they'll. Most of them end up in a very similar state, which is a kind of lockdown state, where there's not really much you can do other than kill it.

But certainly before you get to that point, there's a window of intervention by which you can step in and you can reprogram those cells back to a younger and more functional state, which is what we're doing.

And this is something happening across the body as we age, or does it depend a lot on tissue or organization?

So it happens pretty much everywhere, perhaps different rates in different tissues. Some tissue systems have more senescent cells than others. So adipose tissue, for example, has a lot of senescent cells.

Compared with other tissues, they accumulate in most of your body systems.

And because the signals that they send out into the bloodstream can travel population of senescent cells, for example, in your liver, it's been shown now experimentally that that can induce senescence in things like brains and livers and kidneys. So senescence, I think, is generally when it's unregulated, as a bad thing for systems.

So that's where I think these new approaches that we and others are taking to actually deal with them will allow us to deal with the diseases of aging at their roots, rather than patching up consequences, which is what we do.

Now, you just said that senescent cells accumulate greatly in adipose tissue, which is fat. Can one draw the conclusion that people with a lot of fat age quicker?

This is a bit chicken and egg.

I mean, that's certainly the first sort of interpretation that jumped to my mind when I read that was, yes, you know, if you've got bigger adipose depots and adipose tissue, bigger fat depots, and those fat depots are accumulating senescent cells quicker than folks with more may well be aging quicker. I think the. The complication comes, of course, is that with obesity comes a whole bunch of other stuff.

So actually unpicking what contribution that having too much fat is making directly to aging is. Is actually going to be very difficult when you look at all of the other things that tend to come with that.

So having a lot of adipose tissue quite often goes with low exercise and a poor diet. And both of those things obviously are going to accelerate aging.

What do you think the layperson that knows a little bit about senescence is still misunderstanding about senescence.

So I think the idea that you were able to actually reprogram or rejuvenate these cells until fairly recently has been quite a no. We were, I think, one of the very first teams that actually demonstrated that you could do this in human cells.

And I know we did certainly meet quite a lot of resistance to the idea initially, because it hadn't been reported and the dogma was that they were irreversible. So I think that's, that's something. I think the public are becoming more and more aware of this though.

Quite often in my public talks, I show those pictures with the two mice, the littermates, one of which has had his senescent cells removed. And actually you can feel the surprise in the audience to that concept.

Do you think dysregulated RNA processing is one hallmark of aging amongst many, or something more central? You know, that may be driving quite a lot downstream?

Yeah, I'm probably a bit biased because my lab is a splicing lab. That's what we do before we ever got into any of this aging stuff. That's what we did.

I honestly genuinely think, though it is, it probably sits above quite a lot of the other hallmarks. So it's. We've, we've certainly made a case over the past few years that we think it should be included in the hallmarks.

And I think in some of the newer designations it certainly has been.

But if you bear in mind that 98% of your genes are alternatively spliced, 98% of your genes make more than one thing, and that includes genes involved in every single one of the other hallmarks. So it's something that I think has fingers in all the pies. The other thing with the hallmarks, of course, is they talk to each other.

So they don't exist in isolation.

And if you've managed to have traction on one, and particularly one as fundamental as RNA processing or epigenetics, indeed, then you know, you shouldn't be surprised that you do see traction on the other. So I think it's a central driver.

And at what point did you begin to realize this was not just an interesting molecular detail, but something potentially more important to aging?

Yeah, there's a story here. So my lab are a nuts and bolts RNA biology group. That's what we do. It's real basic science stuff.

I never thought in a million years that we'd actually be having science sort of a real world impact with our research in such a short time frame.

But really for me, where the kind of mind shift came is when we demonstrated that by restoring the levels of these genes that you can effectively rejuvenate cells. So we weren't looking for that, to be completely honest.

I was looking for small molecules that could impact the levels of the genes that are involved in this process. And we did find some.

And to my amazement, actually, what we saw when we were able to do this is that the cells rejuvenated to the extent that when the postdoc who did the work actually told me about this, first of all, I didn't believe her. I thought, well, there must have been some mistake there, you know, there's the wrong cells. But no, it was real.

But that was probably the point at which I started to, to think about this as something that we could actually develop in a sort of a serious setting for the generation of some new medicines.

That's great. Most people, you know, start the other way around. They, they want to fix an issue.

That's what they say they do. That's what they say they do. But actually, quite a lot of advances in science are sort of random luck.

Yes, most of them are. You've certainly sort of got lucky with your research. It's, it's mind blowing there.

So that thinking in your university research led to Sinisca, which is a University of Exeter spinout you co founded, where you also obviously are chief scientific officer. And I guess it has a focus of translating RNA splicing and aging science into potential real world interventions.

In broad terms, what was the thinking behind Sinisca? When did the science begin to feel genuinely translational?

Sure.

So, I mean, the honest story here is when we finally got the first paper published, which took a long time, as I said, because we did meet some resistance, that's when people really started to take notice. We started to get outreach from the commercial sector.

I was probably the most unwilling entrepreneur actually to start with, because it didn't occur to me that this could be a use for this.

So just as the pandemic hit was when we started trying to do this, the very first thing that happened was the university sent us off on a course called iqo, which is an Innovate UK funded endeavor that basically aims to upskill academics in a commercial and translational arena. Because we're not trained for it.

We get trained to do science, we get trained to teach undergraduates and postgraduates, we get trained to sort of peer review and all of the academic stuff, but we do not get trained in how to translate it. It is a completely foreign language to us. And so it's been a real learning curve.

For me, academic research is very, very different to industrial research. So it's taken me quite a while to kind of get my head around that.

For me, in a medical school, you know, that's the first thing I thought about. But actually there are opportunities in all sorts of other things.

The other one that came on the table was cosmeceuticals, which I hadn't even considered, that hadn't even crossed my radar. And the other one is sort of agritech and veterinary. We can't do all of it, of course. So we made a decision.

Obviously my heart is in the therapeutics, that's where we started. But we do have a cosmeceutical arm within the Sinisca.

We are co partnered with l' Oreal to develop some novel skincare which is happening at the moment, which is super exciting, a bit surreal and very, very exciting. But yes, it's been a learning curve for me.

Wow, I can't wait for those creams to come out.

Yeah, you're not the only one that said that.

I think it's very important that the different fields of longevity, whatever they encompass, work together and stop being so siloed. Because obviously the research you do, whether we like to admit it or not, goes across. It needs funding to allow for the research you're doing.

That's true. And I think the other thing, of course, you know, skin is the biggest organ in your body.

Why is it then less worthy of study and of solutions than any other organ system?

Absolutely.

At what point does an academic discovery move from being sort of an interesting science to something that could realistically become a therapy or intervention? At what point in your own mind do you think, oh, we've got something here that's can be applied?

So when you start out, what you've got is an idea and the first thing you do is, you know, you start to make some sort of prototype interventions to get in there. And actually quite often the first ones are sort of just test objects to be able to evaluate whether your idea has legs.

I think when it starts to cross over into sort of a pre clinical development phase is when you've actually got something that you can see a real tractable difference in your experimental system. So we use all naturally aged human cells, human ex vivo tissue, so bits of tissue primarily.

We have done some in vivo because at the moment, you know, I think things are moving in the right direction. I mean, my, my academic lab are animal free. And I think, you know, there's, there's a, there's a merit to that.

The industry is taking a little bit of time to kind of catch up with that, if you like.

But I think once you start to see traction in systems and you have something that you can package up with your intellectual property, you've got your flag in the sand for the idea and you've got something that can be developed. That's when it starts to sort of transition from academia into an industrial setting.

And has seeing the translational side changed the kind of scientific questions you ask in the lab?

100%, I think. Yeah.

When I went into this, I was a very sort of dyed in the wool academic, perhaps a little bit blind to the potential of some of the things we were doing.

What I'm finding now is that the stuff that we're doing on the academic side, and I do still have an academic team, I see potential everywhere in it now, whereas I probably wouldn't have before. So we've got projects on all sorts of things.

And rather than just understanding the biology, what I'm actively trying to do now is to produce ways not just of validating it for publication, but ways that actually we can develop it into something that will be useful in the real world.

And other than your work with l' Oreal for creams, where else do you see this kind of aging science likely to appear?

Gosh. So I think the sky's the limit here, really.

On the therapeutic side, we're starting with a disease called idiopathic pulmonary fibrosis, or ipf, which is a condition of the lung that's basically. Yeah, your lungs become so full of fibrosis that you can't breathe. It's known to be driven by the accumulation of these old senescent cells.

So lots of us in the sort of senotherapeutics arena, people are developing drugs to target Senescence, Lots of us are starting with ipf, but it's a gateway disorder that if we can show some traction and proof of principle there, then that really will open the doors to looking at other things. So that's where we started. But we're also interested in things like copd and we're also interested longer term, in the long term, down the line.

I'm really interested in some of the big common chronic diseases that plague our society. So I think that the approach is valid for even things like dementia, for osteoarthritis, for age related macular degeneration.

I think all of these things actually have the potential that we could treat them with these sorts of approaches.

You're lucky in the sense that your research is hitting the world out there. What can be done to help academic scientists to develop their research, to make it real world, applicable again?

It comes down to training. I was completely unaware that this was a possibility for me and for my team and for our science. We're not trained to think that way.

We think very much in the minutiae, very much in the weeds of what you're doing.

So I think people like me and others like me, getting out there and talking about what we, that we're doing and showing that it doesn't have to stop at the paper, that you can take that science and you can develop it into something tangible, it is a possibility for you as an academic that you can do this. So I think getting out there, talking to other people, showing the way really for others. So I do spend quite a lot of time doing that at the moment.

In fact, I'm doing a talk later on today for some sort of would be entrepreneurs in my community just to show how we've done it.

Because it's not something which comes naturally to most of us academics and you know, to be able to see the potential in what you're doing, I think is a skill that has to be.

Acquired, absolutely acquired and fostered, you know, because the market can't stay siloed.

No.

What usually has to happen between a strong finding in the lab and something that is actually useful in people? And where do most ideas fall apart?

Ideas are cheap and it's very easy to get things to work in your controlled experimental systems in a lab, particularly when you're working with things like cell lines which are really quite well behaved and do the same thing every time you use them.

When you start to advance that idea, for example, out into patient populations, into people, into primary cells, so cells which are basically just out of a person and haven't been cultured in the lab for long, things start to break down remarkably quickly because people are different, cells are different, and then on top of that, you have to layer on when you're working with people. The fact that people don't behave like lab animals do, that they have things that they do that may interfere with your experiments.

Lifestyle factors, you know, lifestyle choices, diet, exercise, all of those things. I think it's actually quite hard to translate things out of the lab without a lot of careful thoughts.

So I think at the moment, one in 5,000 would be drugs ends up actually in the clinic. And I think a big proportion of that fails in the pre clinical phase.

Because those ideas, you know, they may be brilliant ideas, but they're maybe not feasible or they may be too expensive. Because that's the other side of things is, you know, in order for your thing to have traction, somebody has got to want to buy it.

It's no good making the best drug in the entire world if it costs so much that people won't pay to use it on their patients. So all of these things have to be taken in the round.

Rejuvenation, that's a very hot word right now, scientifically, what would count as real rejuvenation for you?

Yeah, it has to have a real measurable biological impact. So I think we hear a lot about rejuvenation. You hear a lot about things like 10 years improvement on an epigenetic clock.

And I think those clocks are really super useful, but they're an outcome measure. They don't tell you about the biology per se.

So for me, for something to be genuinely convincing, I need to see real functional improvement in your test subjects or your patient populations.

I need to see people able to walk further in the six minute walk test or an improvement in the short physical performance battery, an improvement in grip strength, an improvement in immune function. Those sorts of things for me are what I would consider a successful outcome.

Other than the work that you've already mentioned, has anything in this field surprised you? A finding or an idea that made you think this is more important than.

People realize at the moment, I'm constantly surprised by advances in the field. I think that's one of the lovely things about being in the field is that people are coming up with ideas that you never would think of.

So I think there's a number of really exciting ideas at the moment in this space for some specifically. So a lot of our competitors are looking at senolytic, so compounds that will kill senescent cells rather than reprogram them.

And I think there's been some real advances there in being able to recognize different subtypes of senescent cells.

Some of the technologies that are emerging now to look at things like immune rejuvenation and sort of improving your immune function to be able to get rid of senescent cells, I think that's really exciting. Some of the traction that's made in the epigenetic reprogramming, what we're doing is kind of analogous to that, but different.

But yeah, these are things that 10 years ago sound like science fiction.

As we move forward, this is going to move faster and faster. It's exciting times we're in at the moment.

I think from your perspective, what makes a piece of aging science, commercially or industrially or even in the research field interesting without slipping into a hype?

Yeah, I mean, this is a trap that I think we need to be very careful of as a field for our science to be viewed as rigorous and proper, robust science.

So I think that the way to not oversell our findings, and I think it does come down to that, is that the way we're doing things has to fit in with established infrastructure for things like drug development. So we are expected to meet the same outcome measures as, you know, a conventional old school science approach to dealing with things.

So we should hold ourselves to the same standards and the same development pathways or similar development pathways as other drugs. So people who are developing drugs for diabetes, for example, have very well defined pathways to the clinic.

And we need to echo that and use similar outcome measures, similar approaches with ours. We may require additional things.

So tying, for example, an impact on senescent cells to your downstream disease outcome is something that we're going to need to do to convince regulators and patients and clinicians that what we're seeing is due to changes in the number of senescent cells, because patients, typically patients aren't worried by how many senescent cells they have. They're worried about whether or not they've got diabetes or cancer or dementia. Right.

So being able to tie what we're actually doing to what is happening, I think is going to be really important. But this is an expanding field and it's a new field, I think, and this is where some of the hype comes in. So you see this with other things like AI.

I mean, you know, not suggesting AI is overhyped, of course, but I think it's put forward as the panacea and the answer to everything, which it almost certainly isn't So I think we have to be careful and cautious in our science and to hold ourselves to the highest standards to show that this is actually, you know, this is a real approach and not just hype.

Who do you see is lagging behind in understanding what's happening or in moving forward? Is it more sort of the patient or the researchers or the commercial side of it?

Yeah. So in my experience, patients and clinicians are very on board with the concept, particularly for diseases like ipf.

You know, the patients don't have many options, so they're really excited about new things and new approaches that might actually be transformational for them. So that is not the roadblock.

I think the biggest mind shift, I think is going to have to come from the regulators, drug regulators, and also from sort of pharmaceutical partners. So that is happening.

When we first started Sinisca talking to sort of people from Big Pharma, this concept that you could have one intervention that might have multiple applications, might be efficacious for multiple diseases, was a bit foreign to them. Although some of the really big players are now starting to kind of sniff around.

People like Lilly, for example, are starting to sniff around this now. Drug regulators, I think it's an idea that's a little bit alien to them right now.

And the sorts of trials that you'll need to be able to get something as a genuine gero drug rather than a drug for a specific indication, that's where we're going to have to do some work. So at the moment, the regulators are very much designed for. You've got a thing and that is useful for this.

The idea that you have a thing that could be useful for all sorts of stuff is not something they're set up for. You need really big trials.

I also think sometimes the clinical trial design isn't set up for looking at Gerir drugs, for looking at drugs that genuinely target basic biology of aging. In that quite a lot of trials actually consist of mainly of healthy people, even people with diseases.

They're very carefully curated so they're as healthy as possible. Very few trials have older people in, for example.

So if you're developing a drug that is targeted at as a disease that hits people in their 70s, then you need to include people who are older in your trials. So I think there are some infrastructure changes that will need to be made.

Yeah, that would help. Including older people in a study for drugs for older people.

What would a fair skeptic say about this field and which parts of that skepticism do you think are justified?

I think a fair skeptic would question the breadth of what we can do with it. I think it has enormous potential. At the moment, where we are is potential. There are starting to be sort of forays into the clinic.

There are a couple of Senna therapeutics companies now which are in the clinic in phase one, some of them going into phase two even. But I don't think it's going to be the answer to everything. And I think we're doing the field a disservice if we market it as such.

I think there are going to be things that it's going to be excellent for. I also think there are things that maybe we need to be careful not to overhype.

So I think the idea of prevention is lovely, but the idea that we'd start people on these drugs in their 30s so that they never got diseases, maybe it will happen.

But right now I think there's still a lot that we need to understand about how these interventions work and what the long term effects are and the risk benefits, for example, of the longer term. Prevention is something that I think we need to be careful with.

How difficult is it to do human studies? Obviously you're situated in the uk, so let's speak about that. How difficult is that?

So in an academic setting where you can do an experimental medicine study, I think it's a little bit easier in a drug development landscape because of all the issues that we've just discussed with infrastructure, et cetera.

The emphasis is very much on your phase two has got to be patients with disease and your outcomes have got to be disease outcomes rather than age as an outcome. That is something where we are going to meet some resistance because we're not set up for it.

I think what will happen is that these sort of improvements in biological aging will actually fall out of those studies though, and that it will become very evident that people who are taking these, these emerging geridrugs, for a given indication, are aging slower.

You've just said something that I wanted to pick up on. You said aging is not a disease. Do you think it should be classified as a disease?

So I don't think aging per se is a disease. Aging is just a fact. Right. I think senescence and some of the other deleterious things that drive aging should be classified as disease. Yes.

So I think there's a differentiator between aging badly and aging well here.

Does it help or hinder your research the fact that aging is not classified as a disease?

Oh, it hinders it. Because if we were working in Cancer, for example, it would be staged.

I've been involved in some efforts to kind of lobby to have senescence staged as cancer would be staged.

Because then I think it makes it much easier to stratify your populations to make sure you're giving your interventions to the right people at the right time. Yeah, I do think there needs to be thought and work in that area.

If you haven't actually given something, a quantitative measure, it's really difficult to measure it, if that makes sense.

I know it makes a lot of sense. And it also then puts it into the realm of not being real science.

Exactly.

You know, that hinders the whole progress. So is that a policy question that you think the government, you know, needs to work on or where do you see sort of failing?

So, so I think it's. It's a multi stakeholder thing, actually.

Certainly the folks that, that make the decisions, what gets given a sort of a designation, if you like, they certainly need to be involved and active in these discussions. I think, yes, it is a policy thing. And I think, I do think there are some movements happening there. I have done some work with policymakers.

They are certainly interested in it as a concept, I think, because they see the potential, you know, when you look at the numbers in the studies that have been done on the potential financial implications of aging, you know, we're facing an absolute population time bomb over the next 10 years because of the demographic of different ages in our population. And I think that's a very big carrot to hang in front of policy people.

If we're not dealing with these things at their roots and in the way that I think we should be dealing with them, then this is going to get very expensive very quickly for healthcare.

So how do you think we could be able to have better communication and advocacy in the longevity field?

So I think the key word there is communication, isn't it? It's outreach.

I was involved in some of this and asked to go and take part in a kind of aging masterclass to some very important people actually to kind of upskill them and to show them what we're doing and what's possible. And I think there needs to be more of that because if you're not involved in it, you wouldn't know.

And how do we do that? How do we encourage communication?

We need to lobby the people who are the decision makers here to hear us out.

You don't think it's going to fall on deaf ears?

No, I think there will be some deaf ears, but I think certainly some of the People who do matter are listening. You've got to put it in context for them, why it's important, why this isn't just another crazy idea that they should listen to.

What the actual, real, tangible impact on healthcare, on healthcare spending, on social care, on quality of life, what it would be. You need to really spell it out for them, listening.

I'm sure they all do, but that doesn't often translate.

No, no, that's true.

But I think it's about who you get round the table, and it's about getting advocates for whatever you're trying to get out there into the community or into a particular group of people. It's about being able to get the ear of the people who are able to then translate it wider into their own circles.

You need champions and cheerleaders.

Well, the field is counting on you.

I'm happy to be involved.

Tell me now, Art, working so closely on aging changed how you personally think about aging?

Oh, completely. I think it's encouraged me to take more responsibility for my own health.

So I think, like most researchers, I live on caffeine and fast food because time, right, you have to sort of stop and think about what the impact of this is. And certainly I'm. I have over the last couple of years, taken some real steps in my own life to try and make sure that I'm aging well.

I don't want to end up in a situation where I'm 70 and unable to still do this. So, yes, it has made me look at what I'm doing. It's made me look at what my parents and my family are doing.

There are things that you can do without things being really expensive or making a real problem, just to make little things every day to make a difference, sleep time out for yourself, keeping mentally active, being fulfilled in what you do. All of these things are really important. And I think we need to practice what we preach a bit.

What do you think is the one question in this field that is still not being asked often enough?

That is a tough one. So it depends on what area and what group of people you're talking about there.

So if you're talking drug development, I think that how do we harness these technologies to actually make some medicines? I think one of the key questions there for me is about how we can link our mechanism of action to our outcomes. I think that's still outstanding.

I think selling the idea to the community, and I think this is one area where the hype and the snake oil actually does a disservice to us.

Because if we're not seen as serious science, and we're not seen as offering something which actually is a real and feasible approach to dealing with aging, its diseases.

If you've got people out there who are sort of selling miracle cures, promising people immortality without the data to back it up, that sort of thing, I think that's a roadblock.

And I think that's why those of us who are kind of involved in the drug development side of things and involved in more sort of publicity around geroscience and what it can do, I think we owe it to ourselves and to the community that we don't let ourselves get drowned out by people who are promising miracles.

But we shouldn't lose hope that some of these, let's say, crazy ideas do come to fruition, right?

Oh, all of the best ideas were crazy at some stage, right? Absolutely, 100%. I think everything seems unfeasible and unreachable until it isn't. Right. So it's how we communicate that.

I think we need to communicate it in such a way that it's believable and understandable and that people can see the traction.

If you could get one clear answer tomorrow about something in aging biology, what would you most want to know?

I would most want to know if there was a quick, easy, cheap solution that we could apply to everybody that would improve the health of our population as a whole. Because I'm very aware that some of the approaches that we're talking about are not going to be available to everybody.

And I think that, for me is really. It's actually really important to me.

I don't want to generate something which is only going to be of use to a small subset of the population that can afford it. I want to generate something that's actually going to be available to everybody.

And I think what I'd dearly love to know is what the quickest, cheapest, easiest way of doing that is. And it may be as simple as diet and exercise. Who knows?

Diet and exercise has been proven to be a major contributor to longevity. Let me just pick up a little bit on something that you just said.

Do you feel that the field of longevity in the wider sense is becoming something more geared towards the rich, the people that can afford it?

I think that's. That's quite a loaded question.

I have to say that maybe the people with the deepest pockets are the people who feel like they can do something about it, let's say that.

But I think if you've got a lovely life and you can afford to do what you want, when you want, with who you want, then I think, you know, the concept that you could do that for as long as possible is very attractive.

I think if you're stuck in some inner city city, very nose to the grindstone life, where you're on the bread line, then it's not such an attractive option. Right. I think those opportunities need to be available to everybody.

And I think if you're on the other side of the fence from the billionaires, you will feel very disempowered that that's not within your reach. So I think those people don't have the money to be loud about it.

They're not the people who are out there shouting about it because they haven't got the wherewithal to be able to do. So I think it's really important that we take them with us on this journey.

I totally agree with you. The question is just, is that something that is actionable, is it something that can really happen, or is it going to be a two class system?

I think that's up to us. That's about making people aware that this is a possibility.

Because typically some of the people in the most in need in our society are not the people that are going to be listening to your podcast. They're not the people who we're going to be able to access. So I think it's on us to get out there and actually talk to people.

I think there will inevitably at first be who can afford it. Most are going to be the people who benefit most at first. That's just how the world works, right? That's how it has always been.

I don't agree with it, but that's how it is.

But I think as these things become more established, then prices will come down and they will become available to much more people and to many more people.

But I think that's an ethical thing that an ethical choice that we as researchers in this area have to do that we don't just concentrate on things that are going to make billionaires live forever, that we actually expand our studies to things which are available for anyone.

One can tell you're working at a university, because that idea.

I'm an idealist.

Sorry, that's it. No, no, absolutely.

But the question is, and I don't want to push that thought too much, but how realistic is it to bring this idea of longevity to the mass market?

And I don't really mean making people aware of it because I think the majority of people are aware of it, but a lot of them are thinking, gosh, I could just never afford it.

I think in the short term there will be some differences in who can afford and who can't, and there will be people who would love to access the technology and will not be able to. I think that's kind of inevitable in the short term as these drugs sort of come off patent. This is the really tricky thing.

If you're actually talking about developing a pharmaceutical intervention. The money that it takes to do that is huge.

Drug companies, big pharma, they're not going to put billions of pounds into something where they don't get a return. Much as it pains me to say it, it's just economics. So those drugs, when they're first out there, are going to come at a premium. They just are.

Hopefully, if we're delivering them focusing on an age related disease, this is where having a disease indication might be quite useful that they can be offered to people through, for example, the nhs. If we could persuade NICE to allow people to prescribe them, then those would be available to anybody. Right.

So that sort of thing, that sort of thing is one way of doing it.

As things come off patent, of course the prices will come down and I also think there's probably stuff out there now which is much more within reach, which will have a similar impact. So, you know, I'm looking at things like the GLP1 anti obesity jabs.

I think they're gero drugs and at the moment they're still quite expensive, but I think longer term, you know, and particularly when they manage to formulate them in an oral formulation so people can take them rather than just, you don't have to inject, then it will become accessible.

And I think there are other drugs, things like Metformin, really widely prescribed for diabetes, I think in older people that actually has potential to hit some of the same pathways that we and others are dealing with. So I think some of the tools are already out there.

These really bespoke things that people are developing though, those are going to come with a price tag because they're going to come with a price tag because they cost money to develop.

It's very interesting you mentioned the patent and the, you know, on the GLPs, because I believe now the patent is running out on those in India and Canada and I think they, whoever they is, are saying prices could be as low as £15 or something.

Yeah.

Whereas now they're over £200. So there is hope.

Exactly. So your cost of goods for these things actually is pretty, pretty cheap.

Quite often what you're paying for is the decades of R and D that have got into it. So you file your patent, you've got, I think, 20 years from when you put it in protection.

After that time, typically the drugs companies will have moved on to new formulations, new and improved versions of. But those older versions will still work.

And I think those then once they're cheaper and accessible to everybody, you will be able to get them to a wider group of people.

And I always like to end on a hopeful and positive note. So thank you, Professor Lorna, for delivering that. I really appreciate that. I always end with five rapid fire questions for my guests.

So what is the single best piece of advice you would give to your younger self?

Oh, gosh, don't give up. Keep going. Academia and industrial research. I mean, I never would have seen myself.

There have been so many points in my career I thought, what am I doing? Why am I doing this? I could be making so much more money doing something somewhere else. Don't listen to the people who tell you you can't do it.

Name one habit everyone should adopt for a longer, healthier life.

Go to bed at a decent time. Get enough sleep.

If you weren't in longevity science, what career would you have chosen?

So I did used to want to be a vet to the extent that I actually went and did voluntary service in my vet two times a week all through my A levels. So I can see myself doing that if I wasn't doing this.

What Microdose habit, five minute routine or small daily action yields outsized longevity benefit.

So I would have to say vitamin D, within limits. Not too much. You know, you don't want to be loading this stuff on, but most of us, certainly in our hemisphere don't get enough sunlight.

So we're now beginning to understand that actually it's rather than just being a rather uninteresting vitamin that doesn't do very much other than look after your bones, it's actually super important. So I think that one that was probably the sort of smallest and eat food in the state that it's supposed to be eaten.

What's the craziest longevity myth you've encountered in this, Dimitri?

There are so many here. The craziest myth, I guess the craziest myth, that we could just live forever.

That is crazy.

But there are people who think they have their own reasons for doing so. The question about whether or not you would want to, I mean, certainly there are people who do want to.

But I know whenever I talk to the public about this, that's one of the first questions I ask for a show of hands is who wants to live forever? There's maybe two people in the audience put their hands up.

The next question I ask them is who wants to live into an old age without compromise and disease and who wants to have autonomy and health as they age? And everyone's hands go up.

There's a lot of education still needed. I think in general when it comes to longevity, you know what it means?

Oh, very much so. I think people are naturally a bit suspicious. I think, you know, that's because of some of the messaging that has gone out in the past.

I think some of that messaging has alienated the population to a certain extent.

And I do also think it depends what age group you ask because I.

Think if you ask the, yeah, if.

You ask the older age group who's already suffering with, you know, pain and diseases and all that, most of them don't want to live longer. Whereas if you ask, you know, a 30 year old, they'll be like, yeah, let's go for it.

You think you're immortal when you're 30? I know I did. I'm 56 in a couple of weeks.

And in your 50s you start to become aware of your own mortality and you start to notice things that, that weren't bothering you 10 years ago, which now are, I think when you're young, you think, you know, it's not something, certainly it wasn't something that crossed my mind when I was in my 20s and 30s. It was. You just don't think about it.

It's only as you get older and you start to see it in yourself and in your parents and in the older members of your family, you start to see people changing before your eyes. That's when it starts to get real.

Well, Professor Lorna, you're working on combating.

This, so, you know, I'm fine. It's not a short term fix, unfortunately, but I'm going to keep going.

Okay. We're Both in our 50s. We'll get there, you know, before we really need it.

Hopefully by the time we're in our 80s, this will all be long sorted out. I'm holding you to it. I hope so.

Listen, professor, and really thank you so much for coming on beyond longevity. It was such a great conversation, you know, we spoke about so many different things and yes, as I said, I'm going to hold you to it when I'm 80.

Live longer.

You do that. And I hope I'm around to defend the positions so.

Well, let's meet again at 30 years time. How about that?

Sounds good. Let's do that.

Thank you so much.

Thanks ever so much.

Then that was Professor Lorna Harris, and she reminded us that some of the most important ideas in longevity are not always the loudest ones. Because behind all the noise around rejuvenation and anti aging are some very, very serious scientific questions.

What is actually going wrong inside aging cells? What can truly be changed? And how do you turn promising biology into something that improves real human lives?

And Professor Harris is doing exactly that kind of work, not chasing headlines, but trying to understand the mechanisms deeply enough to change what aging looks like in practice. If you enjoyed this episode of Beyond Longevity, please do follow, share and leave a review.

Sa.