Aging Process: 7 Pillars of Health

Steven Gabriel, M.D.

Yeah, so great question, thanks. You know, when I was in the emergency department over the last 20 plus years, I really realized as I was taking care of people that a lot of what was going on at least in emergency medicine as a specialty was just about patching people up so that they could get through to the next day. But nobody was really working on the core process of fixing the people.

Joseph M. Raffaele, M.D.

Right.

Steven Gabriel, M.D.

And how to get people healthier, how to get their cells younger so that they didn’t have to keep going through relapses of whether it’s COPD, some sort of infectious complication, or whatever, other myriad of things people come in to the emergency department with. And a lot of the diseases related to aging, which we’re all familiar with, cardiovascular disease, neurodegenerative diseases, things like that. And I really started thinking, why, as physicians aren’t we looking at how to actually get the cells younger and healthier in a way, how do we get them vital, like they were when we were in our twenties, at least as a direction that we can go in. And as I really looked at that, I started becoming more and more passionate about looking at cellular biology, what was going on and thinking about how to actually get people healing themselves to a certain degree and being able to function and have a life like they did before that everyone really is passionate about.

Joseph M. Raffaele, M.D.

So that’s sort of one end of the spectrum when all hell is just breaking loose in the emergency room to way before I had a similar experience, I was practicing internal medicine for a while there prior to switching over. And yeah, you see that it’s a broken system.

Steven Gabriel, M.D.

Yeah.

Joseph M. Raffaele, M.D.

How would you sort of define the goal of anti-aging medicine and what’s the philosophy around your practice and your approach to it?

Steven Gabriel, M.D.

Yeah, so one thing I think that always comes up and I love that question because I spent so much time thinking about this. Like, what are we really trying to do here? And I really thought about it, and a lot of people get scared ’cause they’ll say, you know, some of my patients have said, even my parents have said, my goal is I don’t want to be 120 years old, right? I don’t want to be 110 years old? That doesn’t sound fun to me. And my answer kind of came back to them when I thought about it, and I said, look, you’d want to be 120 if you felt and looked the way you did at 40, right? So you have an image in your head, and I don’t just mean visual, but just in terms of how you feel, how you look, how you move at 100, let’s say, and that doesn’t sound so fun to a lot of people. But so then I thought, so what is it that we really want? 

It has nothing to do with numbers. It’s really all about what is like a young, passionate, vital life. And I came up with, I put a little bit of this on my website is what is it, I actually went down, I live here by the beach, I’m fortunate to live by the beach here and going to beach. I went down, I just would walk on the beach and look at kind of people at the prime of their life and say, what is their lives about? And I came up with this idea that it is essentially sleep, and I’ll elaborate on these, sex, spiritual, social, movement and nourishment. And when I say, when people say this, they say, well, what do you mean sleep? Sleep, I just mean not just sleeping and the power of sleep, but the ability to turn it off. If anyone’s ever been around a small child, it’s 10 o’clock, they close their eyes, you can pick them up by their leg, they’re still sleeping, adults, that doesn’t work. I mean, I think for most of us we know, we get in bed at night and our brain is still turning. Most of us keep taking sleep aids. You know, you can’t seem to just turn it all off. When I say sex, I don’t mean just the act, that’s what people think, I mean, if you go and look at young people, there’s a sexual energy, tension, vitality to this. 

Movement is just, do you move fluidly, do you feel comfortable, are you the person who jumps in the puddle, or are you the person who steps over it, right? So there’s kind of a different feeling, and so I set out in my mind and said, hey, this isn’t about numbers, this isn’t about age. It’s not about that, it’s if what I’m doing doesn’t move you back on those pillars to where you felt good, at least make some progress there, then we’re not doing anything, right? Because that’s how people feel good, just go out and observe in your own life, and take a look at people, and that’s really the things that it’s about. And so I then took an approach and said, there’s trillions of cells in the body. How can I focus on getting the cells to act more the way they were before so that you feel that way, that you can move that way, that you have a little bit of sexual energy, that you are inspired to go to the party and be social and be around people rather than, oh my God, I can’t believe we have to go to this thing tonight. That’s all a feeling of ourselves and our brain acting the way they did before, I’ll say.

Joseph M. Raffaele, M.D.

Right, no, absolutely. I’ve never heard it broken down into those pillars, but they are really great ones because you’re right. I’ve had that conversation with patients as well. And they’re like, I don’t wanna live to be 120. And I immediately think, yeah, they have a misconception of what it is to be healthy at 120 or that they’re depressed, and just life isn’t treating them well. So anybody that is feeling good about life, wants to continue living, how do we help them do that? So you’ve mentioned sleep, is there a particular approach you take with patients? Is there a-

Steven Gabriel, M.D.

Yeah, sleep’s a big one, and it’s great you said that ’cause we’re talking about TA 65, and actually don’t have it on right now, but I wear a Oura Ring normally to track my sleep. Yeah, there you go. So I don’t know if you’ve done this with yourself, but I’ve done it with myself and multiple other people, patients, family. So one thing I include on sleep is if you do TA 65 at night, and I actually think two pills works better than one, but I’ve found different things with different patients.

Joseph M. Raffaele, M.D.

Two pills meaning two capsules for 500?

Steven Gabriel, M.D.

Two capsules.

Joseph M. Raffaele, M.D.

Of 500?

Steven Gabriel, M.D.

Yeah. If I do two capsules at night, my REM sleep goes up usually over two hours, okay? If I don’t do it, it goes less, go ahead and try it yourself. So there’s something going on there and an immediate effect with TA 65.

Joseph M. Raffaele, M.D.

That’s interesting.

Steven Gabriel, M.D.

It seems to have some effect on the pineal. I combine that with melatonin. If people really have trouble sleeping, inducing sleep, I’ll throw in Benadryl because I find that it doesn’t have any effects on deep sleep or on REM sleep, you still get good sleep. Whereas if you use any of the sleeping aids, the pharmaceuticals, if you’ve ever tried that or alcohol, basically wipes out all your good quality sleep. So you’re unconscious, but no real development is going on there. So, yes, I do, so sleep I basically hit pretty hard with melatonin, TA 65, may use some Benadryl. I also don’t have it on, but I sell some melatonin patches that all night long ooze melatonin in, and it seems to work pretty well for the people who wake up a lot at night. And for myself, I love it. My numbers get better on my Oura Ring. I wish I had the stuff on right now, but yeah-

Joseph M. Raffaele, M.D.

Melatonin right now.

Steven Gabriel, M.D.

Yeah, I don’t want the melatonin right now, but yeah. So that’s essentially where I’d come in with, and maybe I may add on some meditation, but a lot of it, the cornerstone of all of it is cellular aging, all those things I talked about, sleep, sex, social, spiritual movement, nourishment, as I put it in there as a last one. But all of those things, one of the cornerstones is this geno senescence that’s going on inside your cells. So as much as everyone is always trying to do all these supplements and exercise, and different things, the bottom line is your body is programmed to age. And if you don’t kind of try to interrupt some of that programming, it makes it challenging, that’s what I’ll say to him to hit all those other things. You know, just eating broccoli won’t reverse a whole lot.

Joseph M. Raffaele, M.D.

Right, so with the other ones, so for instance, movement, do you prescribe exercise to your patients or-

Steven Gabriel, M.D.

Yeah.

Joseph M. Raffaele, M.D.

Say go to the jungle gym and start running around like a kid?

Steven Gabriel, M.D.

Yeah, I do have an approach to that, so one is, you know, it’s funny we’re on this talk, but really I will say that TA 65 is a huge cornerstone. I also do some other, there’s some other telomere stuff too. I’m also really into senolytics, which could be a different topic, but-

Joseph M. Raffaele, M.D.

We’ll definitely get to senolytics in a bit, but let’s-

Steven Gabriel, M.D.

Let’s focus, so for movement, I do combine some supplements, but the key way that I do a lot of the movement is to do very small amounts of simple things that I tie to something else that you’re already doing. So I’ll give you a simple one that I started with myself. It’s every time I get in the shower, now I do 50 pushups before I get into the shower, okay? I actually started with 30, and then added two a week. And I’m good with 50 right now because I added some other things. So I tie it in no matter what, if I’m late, no matter what I’m doing, if I get into the shower, I have this exercise that takes two minutes, and it’s almost linked up like brushing my teeth. ‘Cause it’s hard to get into something like movement or exercise if you haven’t done it before. All of a sudden you’re signing up for the gym, I’m going to be there four days a week, it doesn’t last. So then later on, I tied in I’m going to do 50 sit-ups before I go to bed. So I linked them up with things I know I do every day, and I put the things on the patients. Then I tie in some stretching, but everything’s tied into a daily thing, and if the person wants to move on from there, they can, but at least you get something in because doing something is infinitely better than doing nothing.

Joseph M. Raffaele, M.D.

No question, consistency is very important as well. Do you end it with a cold shower, or Wim Hof?

Steven Gabriel, M.D.

Yeah, there you go. That’s interesting you say it, so I do, and me personally, I do do at the end of my shower, I blast it with cold for about a minute. But I don’t put that on everyone, it’s certainly not pleasant, but.

Joseph M. Raffaele, M.D.

It’s a great eye-opener, though. Really kind of wakes you up, gets you going.

Steven Gabriel, M.D.

Yeah, do you do that too?

Joseph M. Raffaele, M.D.

Yeah, I do it, I mean, in wintertime sometimes, I don’t do it as much, but I try to do cold therapy as frequently as I can, but you’re right. Sometimes you just don’t feel like it.

Steven Gabriel, M.D.

Yeah.

Joseph M. Raffaele, M.D.

So in terms of your use of telomere biology in your practice, do you do any telomere testing? Have you done any on yourself?

Steven Gabriel, M.D.

So I have done it on myself and I was pretty heavy TA 65 user. And I did have an increase in telomere length, but I personally now have stopped doing testing on patients. And the primary reason is that I’m going to do telomere, what we know is telomere therapy, no matter what. Like, one, it’s relatively expensive, and so for my patients, I say, look, I’ve done this on a few people, I’ve done it on myself. I have the data let’s say with TA 65, I have data with senolytics, I have whatever influence, let’s say, a milk thistle may have or an omega may have, or whatever anti-inflammatories may have on your DNA, I know all those things are good. 

So wherever your numbers are, you need them, you need these things. So let’s just focus and look at how are you feeling with the six pillars, and let’s move forward in those types of places because ultimately it’s not as relevant the number as are we moving along, you need this therapy, I know you do. Even if let’s say you’re a patient who has CMV who loses telomeres at a faster rate, okay, I know you need TA 65, okay? Even if your telomere is a little bit shorter next year, I still know you need TA 65. So what am I changing in terms of therapy based on those numbers. So that’s kind of where I’ve gotten with that.

Joseph M. Raffaele, M.D.

Oh, okay, and you said, so we talked about the sleep pillar, the movement pillar, the spiritual pillar. I mean, interesting that all of these things, various aspects of them had been shown in studies to correlate with slower telomere attrition and longer-

Steven Gabriel, M.D.

Yeah.

Joseph M. Raffaele, M.D.

In terms of the spirituality part, are you’re talking about meditation there or interacting with other people that way, that’s the social side.

Steven Gabriel, M.D.

Yeah, so in terms of the spiritual side, the big thing I say there is kind of seeing the world outside of yourself, this is another thing, young people do this great, this is not church. Now, if it’s church for you, that’s great. So whatever spiritual aspect works for you, there should be some component of it. That means could be meditation, could be a long walk on the beach at night. Some introspective moment, could be church on Sundays. It’s funny you said Wim Hof, my spiritual time, a lot of times doing a Wim Hof breathing because I think it’s very spiritual. But whatever kind of shuts off the world, lets you kind of see a bigger place, I think brings some spiritual perspective. Any one that sounds good to you, I’m not here to dictate what lets you see. So I, for the most part, when I talk to patients, when I talk to people about this, say, here’s a smorgasbord of things that would work, you know, telling someone to sit down and meditate, it’s sometimes frustrating for some people. And I don’t think that’s what you have to do. I can tell people, hey, get out in the woods, go on a trail for 30 minutes, take a walk on the beach. If you really like to do something, do the Wim Hof, it’s great. So all these things are good.

Joseph M. Raffaele, M.D.

And in terms of nourishment, I mean, yes, just eating broccoli is not going to cut it, any other approaches there? Do you have any other testing that you do? I mean, I know a lot of people test for, you have a background in microbiology and molecular genetics you do much with the microbio?

Steven Gabriel, M.D.

Yeah, so I don’t do the microbio, I do look at cardiovascular markers, CRP, all the small inflammatory particles, LDL, those sorts of things. That’s kind of the main areas that I hit there. I will say that in terms of nourishment, I do believe in not long-term, but brief periods of keto to get people started because I think that momentum, when people see results and get some momentum, they tend to go farther because you just see something happening. So I do like keto for that. I do like staying away from animal, if you can, intermittent fasting if people are open to that. I use ProLon quarterly, or if you can just, I don’t know if you know that.

Joseph M. Raffaele, M.D.

Sure.

Steven Gabriel, M.D.

So I’ll use ProLon quarterly, but some people will just say, hey, I can do the five day fast. And I say, you know, have at it.

Joseph M. Raffaele, M.D.

Yeah, I mean, absolutely, you don’t need ProLon if you can do a five day fast.

Steven Gabriel, M.D.

Yeah, if you can do the five day fast, then you should just do it.

Joseph M. Raffaele, M.D.

Have you done a five day fast or only through ProLon?

Steven Gabriel, M.D.

No, I’ve done a five day fast. So what I find with that is three days, the first three days are brutal. The last two are pretty easy. A matter of fact, when I’m on the fifth day, I’m always thinking I could go five more. I seems, but dang, that first and second day, it has to be someone who can, what I say, almost take a couple days off because if you have the stress of work, I think it’s pretty tough.

Joseph M. Raffaele, M.D.

Yeah, I mean, it is a little tough to do that. I mean, I’ve done fast in the office seeing patients, but I don’t have an emergency room type of practice.

Steven Gabriel, M.D.

Yeah.

Joseph M. Raffaele, M.D.

But I think you’re right. In some ways, sometimes being in the office is a little easier because you’re not thinking about food. You’re thinking about getting your work done. Have you done any DNA methylation testing because I know that that absolutely helps with autophagy, which is sort of a major goal with fasting, particularly longer-term fasting.

Steven Gabriel, M.D.

Yes.

Joseph M. Raffaele, M.D.

And that has been shown to improve DNA methylation ages in patients.

Steven Gabriel, M.D.

Yeah, so I don’t do a methylation testing. I mean, I know the benefits of the fasting, and it’s kind of like almost what I’m saying about the telomeres.

Joseph M. Raffaele, M.D.

Yeah, okay.

Steven Gabriel, M.D.

I know this is good for you.

Joseph M. Raffaele, M.D.

Absolutely, yeah, absolutely, that is true. The other, social connection.

Steven Gabriel, M.D.

Yeah, so social connection, I believe once somebody, I find, does, let’s say, a fast, gets on TA 65, improves the quality of their sleep, people tend to have more energy to want to be social. So this is like a tough thing to just say, hey, just get out there and social, I think as people’s body looks better, their energy levels rise, right? All these things happen together. You start to feel more comfortable, more like yourself and more proud, and you feel kind of yourself again. And as you feel yourself again, people tend to all of a sudden say to me, hey, you know, I went out to dinner with the neighbor couple the other day, and I was feeling great, the outfit fit me, I looked good. My hair looks a little bit better. I was giggling a little bit more. 

Usually as you start to feel yourself more, and I tend to feel, you know, I don’t like to say, oh, I focus on weight, but as you do all these things, as you improve your sleep right, thyroid function becomes better, hormone function becomes better, weight comes off, you’re doing a little bit of movement. Especially at the beginning, just do something, a little bit of momentum tends to feed to the next thing and the next thing. That’s why I personally never really push like, oh, you got to get to the gym for 40 minutes a week or something, I’ll start with a, hey, all we’re going to do is how many pushups can you do? You can do 10? You’re gonna do 10 pushups before you get into the shower. And a matter of fact, next week, you’re going to 12 and that’s all we’re doing nothing else. And then the people tend to move from there. How’s your sleep, I put you on TA and some melatonin. How you feeling inside the morning with that? Okay, let’s just add on a Wim Hof, let’s just do that. Okay, now the person starts to say, you know, I didn’t feel like having dessert, and oh my God, I lost three pounds and my pants feel better. And that made me want to be intimate with my wife last night. So you know, all this, I talk about all of it, so a lot of it I think is understanding, wants, and then movement forward from there.

Joseph M. Raffaele, M.D.

Yeah, so it’s a great conversation you’re having with patients to work within their parameters and then have them graduate to sort of improving themselves. So are we missing a pillar, let’s see, food, social, sleep, spiritual. And that was.

Steven Gabriel, M.D.

Did you say sex?

Joseph M. Raffaele, M.D.

Sex, right, so I think we covered most of them. You mentioned that you like to use senolytics, tell me about your experience with that and what are your sort of favorite senolytic substances?

Steven Gabriel, M.D.

Yeah, so that’s powerful too, as you know, because as much as we’re working on telomeres and keeping the telomeres long, and we’re trying to keep the telomeres as long as we can for as long as we can, right? But as telomeres get shorter, as we know, the cells can go into kind of three different phases, it can become like the zombie cell and go crazy, and wreak havoc everywhere, you can apoptosis and die, which is kind of nice. You can just become senescent and sleep, and take up some space. And we’re trying to say, hey, so there was all this work before on telomeres, but telomeres will get shorter. And when telomeres do get shorter, as much as we’re working on them, how are we handling those cells, right? So there’s lots of different ones. If you look at a lot of the pathways, nerve two related, cert related, some, you know, potential rapalogs, you know, if we go down that avenue, which I’ll leave for a different day. But I really like, I generally start people with like quercetin, quercetin and zinc, like berberine, I’ll sometimes throw in like genistein or fisetin for people as well. If I really think that they’re older, they’ve had problems with other chronic diseases. I look at people’s tolerance of how many supplements can you take kind of thing. 

What’s my biggest bang for the buck. I won’t take more than three, then here you go. Maybe I’ll get you on an omega, get you on TA 65, maybe throw you on a berberine or nicotinamide riboside or something of that nature. But for the most part, if somebody’s like really passionate about it, I’m going to have you on what I think saves your telomeres, which might be, like TA 65 is always my start out, we say that’s the cornerstone thing that you should be taking. TA 65, then I may have you on milk thistle to augment. I may then have you with alpha lipoic acid, as some support there. Then let’s tie in some senolytics, let’s get you on some quercetin, maybe some berberine, some fisetin, kind of hit a few different areas there, and do all the lifestyle things that I’m talking about. And that’s, you know, the .

Joseph M. Raffaele, M.D.

And what dosage do you typically use with quercetin and disetin?

Steven Gabriel, M.D.

You know what? I’ve got to go look at my bottles for that because although I wrote them at the beginning when I pick the products that I recommend, now I’m just like, hey, this is the right amount, take two. And I can’t remember the number that’s on there. Just like I don’t remember the numbers on the TA 65 bottle, at the beginning I knew all that. But off the top of my head, I can’t tell you the exact numbers.

Joseph M. Raffaele, M.D.

Some people with senolytics sort of pulse them or do cycles of them. I mean, particularly with rapalogs, there’s obviously side effect concerns with-

Steven Gabriel, M.D.

Yes.

Joseph M. Raffaele, M.D.

And immune suppression, with something like fisetin or certainly quercetin, which is a sort of a milder fisetin, there’s probably not any problem with continuing, some people say, well, do it for a while and then let it go. You don’t have a protocol like that?

Steven Gabriel, M.D.

I don’t have a protocol like that. I say just do it every day. Because I actually think when I look at the literature for some of this stuff that it’s not a 100% clear, I know that they’re good. Especially all this stuff that’s from nature I feel very comfortable with. I always say that it’s funny because when someone’s taking like an omega three, they’ll say, oh, can I take too much? And I say, no one ever asked me if they can eat too many French fries, or have too much ice cream, or how many gummy bears they can have. For some reason we’re not worried about that, but if I take two omega threes, am I gonna get sick? You know, it’s like, I just try to put it all in perspective. The stuff that really comes from nature, your body is really designed to handle. And the amounts inside those pills are not some massive doses if you look at it relative in terms of food. So I’m not too worried about it.

Joseph M. Raffaele, M.D.

Right, right.

Steven Gabriel, M.D.

I am worried about when I put somebody on a rapamycin or metformin, I’m not going to tell that guy, hey, take 2000 milligrams, 3000 milligrams of metformin because this stuff is all more synthetic. So we have to go with the data. When stuff actually comes out of nature and is organic, like what’s in TA 65, we just don’t have to worry as much.

Joseph M. Raffaele, M.D.

So do you do other forms of anti-aging for medicine, such as hormone optimization and hormone replacement therapy, testosterone, or any of that stuff-

Steven Gabriel, M.D.

Yeah, so-

Joseph M. Raffaele, M.D.

With PA 65, with that-

Steven Gabriel, M.D.

Yeah, so I like to see where people will get just doing some basic beginning stuff because a lot of times when you just start, hey, you’re exercising a little bit, losing a little weight, do a week of ProLon, get on TA 65, and we look in a month, usually just making yourself healthier. It’s like, what can your body do if we unleash some of the bad stuff that’s slowing you down. Then from that spot, let’s say, it’s somebody with, you know, the guy’s still saying, hey, I’m worried or whatever. And you look, then I will, generally I’ll go with like an hCG in that context.

Joseph M. Raffaele, M.D.

Yeah, you’re trying to go at the higher levels to sort of fix the problem.

Steven Gabriel, M.D.

Yeah, I like to try to induce your body to make stuff rather than supplement with exogenous. I think it’s better for your glands’ internal controls to handle some of this stuff, that’s the approach I take.

Joseph M. Raffaele, M.D.

So it’s a stepped approach working at the lifestyle, diet, and then supplements as needed, and then pharmaceuticals. Any other pharmaceuticals or biologics that you employ in your practice?

Steven Gabriel, M.D.

You know, I like, metformin is probably one of my more top of my list in terms of, if I was going to say in general, I try to stay away from a lot of synthetic drugs-

Joseph M. Raffaele, M.D.

Pharmaceuticals.

Steven Gabriel, M.D.

But, yeah, pharmaceuticals, but metformin, I do think the benefits outweigh the risk. There’s so much, and sometimes acarbose for people. There’s so much data on insulin spikes are bad, right? I have this joke that I tell people, and I say that, and everyone kind of like, what, I say, food is bad for you. What, what are you talking about? Just telling you, food is bad for you. You need food, but food is bad for you. And it’s kinda like I say, like with a car, yes, the car won’t run with gas, but running the car is what ages the car.

Joseph M. Raffaele, M.D.

Well, yeah, that’s true.

Steven Gabriel, M.D.

All right, so same thing. We need food because we need to run this machine, right? Because ultimately all you’re doing is oxidizing glucose. That’s how the whole machine runs. So you do need to put something in there, but that stuff you put in there is what ages you. So I’m not saying you can’t eat because you have to eat to run the car, but big picture, food’s bad for you.

Joseph M. Raffaele, M.D.

Well, we are certainly an overfed society, that’s for sure, we’re like the ad libitum rats and mice in the caloric restriction studies. And the ones that are actually doing what you do in nature, which is going periods without being able to eat much. And I think humans were optimized to really be in that fasted state for relatively long periods of time, that’s why we store fat. So taking that stored fat and burning it, and then not keeping it at a level of enough stored fat for a year, which is just a lot of adverse consequences. 

So I’ve never heard it kind of put that way, food is bad for you, but I think you’re, certainly insulin spikes are bad for you for the most part, unless you’re trying to shove amino acids into your muscle when you’re a bodybuilder. But yeah, you’ve actually had a couple of pearls here with regard to things to say to patients, particularly like the one where you you said nobody ever asked me if it’s too bad to have too many French fries, and then go onto supplements. Tell me any other sort of things that you do in your practice that our listeners might find interesting that help you manage your patients, and any other sort of marquee supplements that you like to use.

Steven Gabriel, M.D.

Yeah, so other marquee supplements, I personally, I do like NAD stuff. So it’s really popular right now, nicotinamide riboside, right, this is by the kind of Sinclair and Alicia, and that type of group. I actually like changing the ratio of NAD to NADH with oxaloacetate. I think it might be more important than total NAD pools. So I use that, I actually have an oxaloacetate product. I do have a few patches that slowly, you can get antioxidants, or you can get things like curcumin, and resveratrol, and things like that. I think that there’s some benefits there kind of, yeah. Yeah, kind of slow absorption into the skin, small amounts through the day. It’s tough to say, I mean, there’s no doubts things like resveratrol are hugely beneficial. 

The question is, can you actually get it into cells? Right, I mean, there’s no doubt that if we paint resveratrol on cells in a Petri dish and it works, the question is, hey, when I swallow some resveratrol, does it go anywhere that matters? And that’s the problem with a lot of supplements, right? So that’s why sometimes I like transdermal stuff. Almost all that stuff ends up inside your body. I have some interest there. I do like anything that seems to slow telomere shortening. People talking about, okay, can we activate telomerase? Which is what we’re all about with TA 65, and why I think that one’s so important, but people need to understand that slowing shortening can be just as powerful as activating telomerase and lengthening, right, I mean, you get-

Joseph M. Raffaele, M.D.

You wanna do both, yeah.

Steven Gabriel, M.D.

Yeah, I mean, if I never shortened, I don’t even need TA 65, right? But we all do shorten, so we do need it. I do think that there’s also some importance with the effect of chronic infections in our body. Just kind of another phraseology that I use that essentially what’s aging us is inflammation, oxidation, glycation on top of chronic infections, toxins, poor diet, poor sleep, lack of exercise. And so I do like to say for like chronic infections that I have tried with some people, and here’s another pharmaceutical like saying, hey, you should be on daily bowel tracks. I think people are, there’s lots of different, it seems to mostly work on herpes viruses, right? But possibly some effects on some other viruses, and you probably are having some low viral load of things much more frequently than you think. So I think that’s interesting.

Joseph M. Raffaele, M.D.

Just sticking with the Valtrex, and that is something that I employ in my practice as well, particularly in people who carry a fairly heavy burden of herpes viruses, you know, one through six, particularly CMV you’ve mentioned, which is heavy, and Valtrex is not gonna have an effect on CMV, but there is good data-

Steven Gabriel, M.D.

They have some, it may have-

Joseph M. Raffaele, M.D.

Yeah, I mean, yeah, but not like the ones that are used typically that are more toxic, like Aciclovir and Foscarnet.

Steven Gabriel, M.D.

Yeah.

Joseph M. Raffaele, M.D.

But the way it has, I think, potential beneficial effect is by keeping your immune system from being too busy with the other herpes viruses, so you keep them at bay. And then there is an emerging set of data showing that herpes virus one is perhaps a major player in Alzheimer’s disease risk. So if you can keep those from coming out regularly, then I think overall you’re probably doing a beneficial thing for the patient from a telomere standpoint, and then potentially from an inflammation standpoint. So it’s interesting that you mentioned that. I’ve seen observational data where they they’ve seen that people that get treated for outbreaks frequently have a lower incidence of Alzheimer’s versus those who don’t. But I haven’t seen sort of long-term, any kind of controlled trial of course where you’re looking at giving antivirals, such as-

Steven Gabriel, M.D.

Yeah.

Joseph M. Raffaele, M.D.

And long term.

Steven Gabriel, M.D.

When people have CMV, do you treat, like if you just do a test and they?

Joseph M. Raffaele, M.D.

Yeah, I mean, I check everybody for CMV because while it is relatively ubiquitous, it’s about 60% in the U.S. and goes up with age, there are quite a few people who are not CMV positive. I myself in that category. I’m trying to stay that way, but we will see. So I will treat not CMV ’cause the drugs directly are too toxic, but if have particularly high titers of CMV, which means there’s more shedding, more reaction taking place, and they have other herpes viruses, which almost everybody does have. If not one or two, most people have three, chicken pox and many people have. And HHV6 is quite common as well. So to keep that burden down, and I have seen titers get less with that approach. And I don’t think there’s any sort of long-term adverse effect from it, so I do. But I wish there were better drugs for CMV ’cause it’s a big, bad actor.

Steven Gabriel, M.D.

So you just use the Valtrex?

Joseph M. Raffaele, M.D.

Yeah.

Steven Gabriel, M.D.

So I also will throw in like fulvic acid because there’s a lot of stuff with that about effecting viral binding to the receptors on the outside of the cell.

Joseph M. Raffaele, M.D.

Oh, I’m not familiar with that. Do you have any, fulvic acid is?

Steven Gabriel, M.D.

Yeah, it comes like from like soil. And if you just take a look at it, humic and fulvic acids.

Joseph M. Raffaele, M.D.

Oh, you’re talking about the stuff that Zach Bush uses.

Steven Gabriel, M.D.

I don’t know Zach Bush, I just look at literature and then when I find the stuff that looks like it will support it, I’m like, okay, is anyone making this, right? Can I get some, and then I’ll use it. Actually, I think that chronic infections definitely plays a role.

Joseph M. Raffaele, M.D.

There’s no question about that, yeah. I think chronic infections are load, either viral or bad players in the microbiome, or intracellular pathogens like Lyme, and the et cetera. Certainly I think increased inflammation and ’cause the immune system to be working and-

Steven Gabriel, M.D.

Yeah.

Joseph M. Raffaele, M.D.

Increase in senescent cell burden. Yeah, I think that medicine needs to be more proactive about that and looking at sort of, it’s good to get exposed when you’re younger, so your immune system can develop some tolerance, but later in life, which we weren’t really evolved to be alive, that chronic burden, I think, really. Maybe one of the reasons that we see differential response to COVID infection even in younger people, they may have a heavier burden of infections. They may have more senescent cells, shorter telomeres. And again-

Steven Gabriel, M.D.

Yeah.

Joseph M. Raffaele, M.D.

So I think definitely that’s something that I do in my practice as well. Well, very interesting. So any kind of an anecdotes in terms of patients besides the REM thing, which I’m going to definitely look and see, I haven’t been taken T 65 at night. The company’s agnostic about when you should take it. Some people find it a little bit activating at night, but that’s a small proportion of them. So it would be interesting to see if the-

Steven Gabriel, M.D.

Yeah, almost everyone I know who has an Oura Ring, when I put mine on, has gotten some benefit. It’s interesting. I will start hitting two and a half to three hours of REM if I take like three of them, it’s pretty. But it starts stealing from my deep, I find, stealing from my deep.

Joseph M. Raffaele, M.D.

Right, that’s interesting, yeah. So you want both, you definitely want the deep for sure. Yeah, it may be because it’s a little activating potentially. It’s hard to say. I mean, mostly TA 65 is fairly inert in other systems. We think de-repressing the repressor and the promoter for telomerase, but there’s certainly these non-canonical, off target mitochondrial effects and antioxidative stress effects. So who knows, I have a fair amount of data, I have a fair amount of patients, have some of them try taking it at night. That’s a really interesting thing to give a trial of.

Steven Gabriel, M.D.

Yeah.

Joseph M. Raffaele, M.D.

So really it’s been great talking to you. And do you have any closing thoughts about where are you going next with things and telomere biology.

Steven Gabriel, M.D.

Yeah, yeah, so for telomere biology, I believe really at the end of the day that it’s our geno senescence or aging of the DNA that is ultimately aging us. All the theories, and I don’t want to say any of them are bad, there’s no doubt we’re oxidizing over time. All those things are true, but the real thing pushing you down the rabbit hole is that our DNA is designed to age the cells. And people ask, well, why would that be there? And it is, I believe, for evolutionary purposes, it’s based on how long should people be around with changing environments so that we can pick up different methylation patterns and different things, and some evolution of our species to keep the species alive. 

So if we’re going to focus on this, it really has to be at the DNA level. I think that a lot of this stuff, I think there’s no doubt that the cornerstone of this is really all about keeping the telomeres long. I think there’s a lot of data to show that. I think that this combined with some of the cool stuff that’s coming off about affecting mTOR, and how we’re going to do that all combines with this, and also how we keep our insulin spikes low. The clearest body of evidence really surrounds, I would say, those three things, and hitting those three things early and effectively is obviously the most powerful thing we can do in terms of us hitting what is, I would say, having a younger, more vital, energetic life and forget about the number, Just forget about the number.

Joseph M. Raffaele, M.D.

Right.

Steven Gabriel, M.D.

The goal should be about, and I’m going to put it ’cause this is my part, those six pillars are you moving towards those, are those staying vital in your life? And if you’re doing things that are doing that, I think things will be pretty good.

Joseph M. Raffaele, M.D.

We’ll end on that very positive, interesting note. Thank you very much for being on, Steven.

Steven Gabriel, M.D.

All right, thank you so much. It was great talking with you.