Episode 198: Multi-Organ Age Clocks (SYMPHONYage) w/ Hannah Went

In this episode of the Aging Well Podcast, Dr. Armstrong is joined by Hannah Went, co-founder of TruDiagnostic, to explore the fascinating world of epigenetic testing. They delve into how TruDiagnostic's cutting-edge kits provide deep insights into biological age and health metrics influenced by lifestyle and genetics. Hannah explains the comprehensive reports generated from these tests and discusses Jeff's personal results, highlighting the differences between chronological, biological, and epigenetic age. The conversation also covers the future of healthcare and preventative measures based on epigenetic data. Tune in to discover how personalized epigenetic insights can help you make optimized health decisions and... age well.

Check out Hannah Went’s podcast, Everything Epigenetics. 

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Transcript

0:05

In this episode of the Aging Law Podcast, I'm joined by Hannah Welt, co founder of True Diagnostic. True Diagnostic offers advanced epigenetic testing. The advanced epigenetic testing kits offer a deep dive into your biological age. influenced by your lifestyle and genetics and provides a detailed analysis of various health metrics. It provides a comprehensive report grounded in cutting edge research that offers personalized insights into how to optimize your health based on your unique epigenetic data. We discuss the results of my recent test in episode 162. In this episode, we discuss the 11 Organ Epigenetics Report that was recently added to the True Age Test and how these scores can inform us in affecting our lifestyles to age well.

jeff_1_10-04-2024_093316: 0:50

So Hannah, welcome back to the Aging Well podcast. Before we start, let's give the listeners a refresher about who you are and what your role is at True Diagnostic.

hannah-went--she-her-_1_10-04-2024_123316: 1:01

thanks so much for having me, Jeff. I'm excited to be here. I'm Hannah Went. one of the co founders at True Diagnostic, and the director of our clinical testing arm. we are a company that offers advanced analytical epigenetic testing, focusing on biological age outcomes. this is a really big buzzword right now. It's this new novel sexy test, almost like a party trick in some case for people. But what we know about these algorithms or epigenetic clocks is that they're super, super useful in predicting really your risk for every single disease state and even death itself. So I'm sure we'll, we'll hop into that a little bit further on the show today.

jeff_1_10-04-2024_093316: 1:49

Yeah, so in that was episode 162 that we discussed my True Diagnostic test. And I want to interject right here that we are an affiliate with True Diagnostic and offer a 12 percent discount on testing with the promo code agewell. And so since that time, True Diagnostic has added an 11 organ system analysis to the report. What is Symphony Age and why is this such an exciting addition to the True Age test?

hannah-went--she-her-_1_10-04-2024_123316: 2:21

Yes, this one is, is really, is really nice overview of how you're aging. So we just released this at the beginning of July this year, and it's the aging of 11 different organ systems. this is exciting for, a multitude of reasons. The biggest reason being that different people age differently, right? And we're able to actually capture that. symphony stands for your system methylation proxy of heterogeneous organ years. Again, very simply understood by us just looking and examining how different parts of the bodies age. So scientists at Yale, Dr. Morgan Levine, Dr. Albert Higgins Chen and his team, postdoc student, Raghav Sigal, really use this method to study 11 different parts of the body, to see how we age differently. this includes the age of your immune system, musculoskeletal system, Brain, kidney, metabolic, inflammation, lung, liver, blood, heart, and hormones. it gives you a nice platform to dive in and say, why and how am I aging faster depending on, which organ system is aging the fastest. You can then intervene with targeted, treatment therapies

jeff_1_10-04-2024_093316: 3:47

Okay, so originally I had just taken the original True Diagnostic test and then you had since then added the Symphony Age report. before we dive into my results Let's talk a little bit about biological clocks. What is a biological clock and how does it differ from one's chronological age?

hannah-went--she-her-_1_10-04-2024_123316: 4:07

Yeah. To recap we have many different ages in our body, we can measure our biological age by looking at, checkpoints we want to look at along the way. you know, how predictive are these algorithms, how accurate, precise, reliable, sensitive they are. do they respond well with interventions and in the correct direction that's why we measure that through epigenetics. most people are used to your chronological age being how many birthday candles you're blowing, off your birthday cake every year. Really it's only a linear process that increases as time goes on. You become older and older. It's How many trips we've taken around the sun. But the idea of biological aging is that, we differ on a cellular level, just sit back and think of how old you are. Chronologically, if you think of how old you are, think of your friends who are also your same age peers, family members, sometimes those people, the same chronological age look way older and sometimes they look way younger. This difference is due to, um, not some chronological difference, because we know that's the same, um, some underlying biological difference. and we're able to really, again, quantify that now through these epigenetic mechanisms, or your kind of on and off switches on your, your genetic level.

jeff_1_10-04-2024_093316: 5:24

what inspired the development of symphony age and how does that differ from The other biological age testing measures or methods included in true age testing

hannah-went--she-her-_1_10-04-2024_123316: 5:34

I think we've always understood that people age differently, right, coming back to that idea. Not everyone gets lung cancer at the same time. Not everyone gets liver cancer has kidney issues at the same time. So we come back to this difference of heterogeneity, in your individual organ system. So just having one number, one biological age. really isn't enough, right? People live differently. Some exercise a lot and keep their bodies younger, while others might keep their minds super sharp, but they might not eat as well, which can make other in different parts of the body age faster. likewise, if someone smokes or drinks a lot, it can speed up aging in their lungs, heart, liver, or brain. treating everyone the same when it comes to aging doesn't really make sense. it's crucial to note that our body systems don't age in isolation. There are many, many, many age related illnesses that stem from issues in various biological systems working together. for instance, arthritis is the result of both wear and tear and inflammation. stroke on the other hand can happen due to problems in your cardiovascular system, metabolism, inflammation, and overall brain function. So these interconnected patterns can lead to different aging types, making people more prone to certain age related diseases and understanding those patterns help in forecasting certain health outcomes. So I'll even give you 11 last example, Jeff to which is again, take two people who are 50 years old chronologically. for example, They're the same. chronological age. Patient A, is a smoker, has an unhealthy diet. This leads to a high metabolic and lung age. So the patient's risk in this case for lung cancer, COPD, diabetes, that's increased due to advanced lung and metabolic aging. If you take the next patient, let's call in patient B, they have a really healthy diet and exercise. and they do this on a daily basis, They're still 50 years old chronologically, but their lung age is 46 and their metabolic age is 45, meaning they're gonna have a decreased risk for lung cancer, COPD and diabetes, right? Which is, again, I think super, super important as we decide. About the type of life we want to live what supplements we want to take if we want to engage in any type of medication or pharmacological as well as maybe more of those procedural based treatments,

jeff_1_10-04-2024_093316: 8:11

can you walk us through how symphony age works and what specific markers it measures?

hannah-went--she-her-_1_10-04-2024_123316: 8:16

the symphony age works in the same exact way, as the rest of our testing does. So I'm not sure if you're asking, how it works in terms of sample collection, or the process.

jeff_1_10-04-2024_093316: 8:28

what is it looking at in the cells or in the blood that gives us the markers relative to, the liver, the lungs and so on.

hannah-went--she-her-_1_10-04-2024_123316: 8:35

thanks for the clarification So again, we're looking at system specificity, to get, an idea of specific functions. We want to preserve specific diseases. We want to prevent specific actionable biomarkers. We want to look at, and combining it right with molecular markers. As you mentioned, Jeff, to quantify aging, we're capture molecular hallmarks of aging and even doing that in a single blood test, as you mentioned, not, a puncture in the veins, but just a finger prick. in order to build symphony age, we actually looked at 133 clinical chemistry and functional biomarkers in the health and retirement study. we categorize these into 11 systems. through our prior clinical knowledge and additional literature research. I'll give you some examples, of what that actually looks like, for lung age, we're looking at how much the person has smoked across their lifetime. if they had previous incidents of lung disease, chronic respiratory symptoms, bicarbonate, you know, P. F. R. And then we're looking at kind of, the methylation markers of those particular signals to create that long age. for blood age, we look at hemoglobin, hematocrit, red blood cells, red blood cell distribution with, We look at mean corpse, corpse, your volume, ferritin, platelets. and even brain, we look at BDNF, clostridium stroke, homocysteine, overall cognitive scores, you know, heart. We look at homocysteine, BMI, C. systolic and diastolic b size, circumference o and a lot more. So ca of get an idea of the dif we're looking at to creat scores. and just regr way. We only need DNA met to predict those, those i so I think you, you u it measures. So I named a about, you know, thre

jeff_1_10-04-2024_093316: 10:39

Is it a synthesis of all these different individual organ clocks? Or is it, you know, specific research or there's some specific research or validation, studies that have been conducted more specific to symphony aging how do we know the accuracy and the reliability of symphony age?

hannah-went--she-her-_1_10-04-2024_123316: 10:57

Absolutely. So remember how we train these, right? We're integrating biomarkers into a unified component, for heart we're looking at, things like BMI, homocysteine, waist circumference, blood pressure, heart rate, you know, smoking history. We're then building DNA methylation proxies of heart components. And then we're combining those heart component Proxies into a heart death or mortality risk score. we're able to, validate these clocks by, using, six different cohort studies, W. H. I. B. L. S. A. S. A. T. S. A. And more. there were over 8100 DNA methylation samples across these studies, and there were 28 different aging phenotypes associated with the clock. So not only that, but we quantify specificity when each of these clocks, right? So are we able to predict specific, phenotypes with these outcomes? absolutely. we know, for example, our brain score is most predictive of cognitive function, musculoskeletal for physical function, inflammation, heart, musculoskeletal for overall total comorbidities. we can name more Lung for lung cancer, blood for leukemia, hormone age for breast cancer, heart age for coronary heart disease. hormone for thyroid, musculoskeletal for arthritis, and so on this specificity is replicated in outside cohorts. it's, noteworthy to say, we get the same, data back no matter which cohort we're testing it in.

jeff_1_10-04-2024_093316: 12:32

Okay. how should individuals use symphony age And how can they take these results to make actionable changes in their health and lifestyle? Because that's really what we want, our listeners and viewers to be doing taking the test and then using it to age well.

hannah-went--she-her-_1_10-04-2024_123316: 12:47

So. I think one good point is how we can take these biomarkers to anti aging interventions is kind of what you're asking. So remember, most of the measure biologic aging in just one whole score, right? And that's great if an intervention is affecting your whole body aging, in which the clock would capture that change. But there are many scenarios. where specific interventions have specific effects on systems, So a whole body clock may not measure that change effectively. we may require system specific clocks to validate that hypothesis. We've done this. Right. And with our collaborators at Yale, where looked at a few longitudinal studies, where an anti aging intervention, let's take metformin, for example, was given for a fixed period of time to individuals and their whole blood DNA methylation was collected. before and after That way we can calculate the accelerated scores for each individual and do, paired bioinformatic analyses to see if the scores were changing with the intervention when we look at metformin, if we took, 10 of the biological age clocks, there's only one clock out of all 10 that actually capture that change. Doesn't make much sense, right? We know metformin does have some anti aging properties and we should see that being reflected in a lot more of the clocks. what we did is actually then apply symphony age scores to this intervention with the metformin. And saw a lot of the down. six to be more specific. We saw The blood score go down, the brain score go down, inflammation, heart, kidney, and metabolic. So we know Metformin has the ability to decrease specific aging scores. when people want to get more specific in their regimen. this is what they should be using the score for, we know your lung score decreases the most with smoking cessation. We know metabolic score decreases the most with gastric bypass. and then out of all the ones I named for metformin inflammation and metabolic scores decrease the most with metformin too. it's really useful. if someone's wanting to get more specific with their particular routine,

jeff_1_10-04-2024_093316: 15:01

Okay, you ready to dive back into my results?

hannah-went--she-her-_1_10-04-2024_123316: 15:03

let's do it.

jeff_1_10-04-2024_093316: 15:04

All right, in my original report, I learned that I'm aging pretty well. my, Dunedin pace of aging score was 0. 85. And I think that's fairly decent. I'm aging at a little bit slower rate. I always forget how to say this. It's the ominin m age. How do you pronounce that again?

hannah-went--she-her-_1_10-04-2024_123316: 15:22

It's the omic M eight.

jeff_1_10-04-2024_093316: 15:24

The omic age was 55. 87, and I'm 61. My telomere length was, 7. 11 kilobases, giving me an estimated telomere age of 51. 11. So overall, my scores indicated pretty good longevity profile. So when I got my symphony age report, I was a little bit surprised that my musculoskeletal age was 65. My inflammation and metabolic ages were both 61. And then my other organ systems indicated more youthful scores. My lung and liver were 54. My kidney and brain are 54 as well. My immune system is 58 and my heart and hormones are 59 and my blood 60. So a little bit different than I expected, especially considering that my biggest focus in exercise has been the musculoskeletal system, lifting weights and those types of things. The metabolic doesn't surprise me so much because I've had a lot more difficulty recently trying to lose weight. my weight just won't budge no matter what. in the previous scores, it revealed that I have a bit more difficulty if I'm going to try and lose weight by just going hypocaloric inflammation probably is not unusual considering that, about the time I took that test, I had, you know, shoulder issues going on where I had a lot of inflammation in my shoulders. One really cool thing I like about the report is that it places the organ systems in that circle. I'll share this in the video format of this interview so people can see my results in that regard. it allows us to see where the balance of those systems are. what can I take away from this report?

hannah-went--she-her-_1_10-04-2024_123316: 17:13

Yeah, I think, summarizing what you said, Your musculoskeletal age is going to be the highest, so that is what you would want to focus on just because that's going to be what's driving your kind of overall symphony age score. depending on where that's at. I don't know. I don't know if you mentioned where that overall symphony age score is. we want to focus on driving What's the highest? with your musculoskeletal age, I remember you talking about your shoulder the biomarkers that that play a role into that include, vitamin D three, dehy, dehy. Epi Androsterone sulfate, IGF one, arthritis height, weight, BMI. and then really just a ton of like, exercise-based outcomes. So mobility movements, hand grip strength, maximum measurements, balance test, timed walk test, previous back problems, kind of crouching. one legged tests, chair climbs, climbing stairs, even a lot of weight lifting as well. Maybe some of you are familiar with the sum of seven different functional tests and a combination of all balance scores. this is a well, created marker. most predictive of overall physical function, total comorbidities, diabetes and arthritis. Again, maybe it's a reflection of having issues with your shoulder, and limited mobility in that realm. I'm not sure how much you've changed your exercise regimen up until that point, so that would be interesting to talk about.

jeff_1_10-04-2024_093316: 18:39

I think at that point, I've been exercising pretty consistently throughout and, strength wise, I'm well above probably my age category in terms of my strength, my mobility, my flexibility and things are pretty good with the exception of shoulder issues. I have a type three acromion and so that's just left me to be prone to, you know, shoulder injuries. I had rotator cuff surgery on my right shoulder. I think I've had some labral issues over the last couple of years. And I think part of it may be, and this is kind of one of the questions I had for you, is is it possible that the timing of my test could have had some impact on that individual organ system? my overall scores were really good. when we looked at grip strength and a lot of the physical parameters in the overall test, everything looked pretty good. My cardio was a little bit higher than I wanted it to be. we talked about the fact that I probably need to do a little bit more cardio and I've started doing more of that. I've shifted a little more cardio. keeping the weights the same. Done a few other interventions to deal with more of the inflammation. And maybe even the metabolic side of it. I'd be curious where things are now because, it was taken at a different time. But is it possible that the nature of when I took the test could have an impact on those scores

hannah-went--she-her-_1_10-04-2024_123316: 20:01

unless you're doing something, dramatically different. we measure an I. C. C. Value for precision of these scores. Meaning if you took two samples at the same exact time, how highly correlated are they to one another? in our case, all the algorithms and biological age clocks we use at True Diagnostic, they're essentially perfect. so, you know, unless you're doing something, that is a really large change, to your routine, the scores aren't going to change too much.

jeff_1_10-04-2024_093316: 20:59

So any other kind of take home I could have from that? I mean the fact that i'm 65 in the area that I feel like I should be the best in

hannah-went--she-her-_1_10-04-2024_123316: 21:06

I think, outside of the musculoskeletal age, if you haven't already done tests for vitamin D, IGF 1, those are some biomarkers to look into, because those are, you know, used in the creation of the musculoskeletal score. But you also mentioned, you know, inflammation in, in metabolic ages too, which again just screams to me kind of injury, right? Musculoskeletal inflammation, metabolic, so in your, your metabolic score, you, your previous smoking status, diabetes, diabetes, CRP, fasting glucose, cholesterol, triglycerides, IL 6, BMI, waist circumference. and then you also have, an inflammation kind of, again, those things. same factors, ferritin CRP, transforming growth factor beta IL 10, interleukin one receptor, antagonist IL six tumor necrosis factor receptor one. So again, more of that inflammation, right? It sounds like there's a healing process going on there. So, maybe focus on just overall healing, especially within that shoulder. I forget when you took the test though. Jeff, when did you take it again?

jeff_1_10-04-2024_093316: 22:10

That's a good question. let me see. I think I have the report here. I don't know if it gives me a date on it.

hannah-went--she-her-_1_10-04-2024_123316: 22:17

it should be at the top there.

jeff_1_10-04-2024_093316: 22:19

I think I've only opened up the Symphony Age one, but

hannah-went--she-her-_1_10-04-2024_123316: 22:23

Yeah, it would be at the top or it definitely should be, the reason I'm asking is because, You know, we, we definitely want to retest probably every six at, you know, the, the bare minimum, you know, you can even do it sooner every three to four months if you really wanted to, and then, at least once a year, once you start to regulate a lot of these markers, it'd be nice, if you made a change between both of them to retest.

jeff_1_10-04-2024_093316: 22:46

yeah, so I, I would be very curious in kind of how I've improved over that, that period of time, cause I do think, and I think it was the score on the, on the, the date on the top, but I don't know if that's when I printed it was, like eight early, eight would be what early July, I mean early September. I think I took it earlier than that. It must've been July, I have a good friend of mine that also I took and in fact, he's the one that kind of introduced me the fact that the symphony age was coming out and I jumped on it. Adrian, he has an overall symphony age of 46 and he's testing age is 50. he said all his blood, kidney, immune, you know, brain all were all higher. the rest were lower, with lung being at 42. he mentioned it's great to know that the four that are high and take and taken together all point to an increased risk of leukemia, which says as scary as my grandmother on my dad's side died from that. And my dad had somewhat related non Hodgkin's lymphoma. So for him, it's kind of revealing that, okay, I need to get a little bit more serious. I have to consider that I am at this higher risk genetically. I think that's what the intention is of having this symphony age, you're looking at what's my family history, where am I at presently? What am I doing lifestyle wise? as we do this multiple times over the course of the year, we're actually seeing. how we are working toward improving our current health systems to promote longevity and healthspan.

hannah-went--she-her-_1_10-04-2024_123316: 24:15

yeah, thanks for sharing. we get stories like that all the time, I did a report review call today with someone whose blood age was the highest. he's like, well, everything that it's trained off of looks in range for me right now. I'm like, well, the blood age is actually still super predictive of, leukemia, as you mentioned. the same story you're telling here, they had some type of, blood cancer in the family. He mentioned that his, his father and his grandfather had. So it was a wake up call to him. Like, hey, there's more to this. He was someone who was not really, physically fit or, working out in that area. And that's low hanging fruit, That can change that score. it, gets everything on, a tangible playing field for you to start to implement changes and retest over time.

jeff_1_10-04-2024_093316: 24:57

what do you see as the future of epigenetics in the context of aging and personalized medicine, especially as we consider this symphony age score?

hannah-went--she-her-_1_10-04-2024_123316: 25:06

I think, the future of epigenetics in the context of aging, I, I think we're already there. I, I think we're You know, we, we are in the future now where we feel very confident in these aging scores. in terms of, research and development with aging, you're probably going to see that slow down a bit just because we're super confident with what we've created. We will still be looking into it, but I think we're just more excited of. using epigenetics outside of aging as a new and novel biomarker. we have some really cool products coming up that are more nutrient specific, antioxidants, kind of vitamin level reporting, and then specific risk scores too within individual disease states that will take through the FDA approval process. I think regarding personalized medicine, It's just a maybe a process of implementation with the health care providers, and all the way down to the consumer we're doing a lot of things educational wise, to hopefully make that happen.

jeff_1_10-04-2024_093316: 26:01

how do you envision the role of biological clocks evolving over this next decade, particularly in the field of preventative healthcare?

hannah-went--she-her-_1_10-04-2024_123316: 26:09

I think the longitudinal data is what's super important. being able to initiate a lot of these randomized control trials and say, Hey, we saw a really good scores with these clocks clocks are essentially a stick for people now and they really no longer hav 40 60 years to see how ho over time. these cloc Speed that up. but I still think, you know, we, able to follow up with those cohorts longitudinally over time is, is a huge, huge need.

jeff_1_10-04-2024_093316: 26:42

are there any upcoming innovations or research coming out of True Diagnostic that you're particularly excited about?

hannah-went--she-her-_1_10-04-2024_123316: 26:48

absolutely. So, so the ones that I, I just mentioned, right, is, is us just using epigenetics as a biomarker for other outcomes. we'll have a new product here in No Carter true eval repo a personalized report bas that really aims to i the levels of crucial bio well being related to, you know, categories such as vitamins, amino acids, methylation, antioxidants, minerals, healthy fats, additional systems and other conditions too. So, we're super excited about that. And then getting more into those methylation based risk scores, where we are, are able to, tell you your, absolute risk for individual diseases.

jeff_1_10-04-2024_093316: 27:37

Okay, and you already told us in episode 162 that you're doing pretty well. They're doing pretty good personally to age well, the listener will have to go back to that episode. So I won't ask that question like I ask of all my guests because you're a repeat guest here. But has anything changed in kind of your health habits and what you're doing to age? Well

hannah-went--she-her-_1_10-04-2024_123316: 27:54

Oh, if anything, it's gotten worse over the summer because it's been so nice out. I haven't been, strict on my exercise routine or diet, but I think it's about, giving yourself grace, and not. stressing too much I think a routine is really important. I'm still, staying, pretty regimented with my meditations, but I definitely need to get back into the lifting routine and, going to the gym daily.

jeff_1_10-04-2024_093316: 28:21

I have increased my cardio. I'm trying to do a little bit more walking, not really hard cardio, but doing that on a regular daily basis. like I said earlier, my weight hasn't really budged. I did recently, and I know you've done some work with, El Nutra, but I had, Dr. Antoine on the show and I did one of their five day fast actually lost about 10 pounds on the fast Gained a little bit of it back. I haven't been able to budge from that point again Which goes back to I can't do much with caloric restriction I have to figure out what else I have to change to move that a little bit more and get my metabolic age back down some. this has been a really fascinating and informative discussion. Is there anything else you'd like to add?

hannah-went--she-her-_1_10-04-2024_123316: 29:07

No, I don't think so. It's been great. Thanks for, having me on Jeff or, anyone who's interested in testing or, maybe just curious. I definitely encourage you to, I think the first test is really eyeopening as, as a baseline. And then, you know, you'll start to test longitudinally and see what really works for your body, which I think is the most important part.

jeff_1_10-04-2024_093316: 29:26

I think it's very helpful if anybody is planning on going down a path to improve areas of their health. To have markers that can tell them whether what they're doing is beneficial I do think the true diagnostics testing is a great way to do that. I encourage the listeners and viewers to check out the true diagnostics webpage they should also check out your podcast, everything epigenetics. they should check out the true age test. And learn more about their biological age and get their symphony age, 11 Oregon ages and Dr. Wine again, thank you for joining us and just keep aging. Well,

hannah-went--she-her-_1_10-04-2024_123316: 30:05

Thanks, Jeff.

30:07

Thank you for listening. I hope you benefited from today's podcast. Until next time, keep aging well.