#444 The Best Bloodwork for Longevity - Dr Michael Lustgarten

Dr Michael Lustgarten (0:00)

Eat real food and exercise. Everyone that's ever used that approach has died, right? So, but there's gotta be a deeper layer. What are the biomarkers of this cachexic phenotype where you're just decaying, you're still alive, but you're basically literally dying and decaying and decomposing over a 10 or 15 year period?

Siim Land (0:17)

Michael, welcome back to the show.

Dr Michael Lustgarten (0:19)

Hey Siim, thanks for having me back.

Siim Land (0:21)

Yeah, I'm excited to have you back. And yeah, this is our third episode, or even fourth, I think. And yeah, like I always have you back, because we never go into all the details that we want to talk about, so we need separate episodes for different topics. And yeah, this time we wanted to talk about blood work, which I think you and I agree that it is one of the most important things for your, let's say, longevity potential. So like if knowing which direction are you heading in, like are you heading in the wrong direction or in the right direction? And blood work is kind of a reflection of your inner health as well. What is your, like, I guess, philosophy when it comes to blood markers? And how would you like to prioritize it?

Dr Michael Lustgarten (1:09)

Yeah, perfect. First question. So let's frame it as the health and potentially longevity hierarchy optimization, right? So I see body composition, right? So leanness, relatively low body fat, low visceral fat, relatively high bone mineral density. But then it's not just one time point. It's avoiding age-related changes, right? So loss of lean mass, resisting age-related increase for body fat and visceral fat, decline for bone mineral density, right? That's at the top of the hierarchy, optimizing that. Also physical fitness, right? VO2 max, grip strength. And then, you know, as a harder to measure aspect, cognitive function, right? Because who wants to be fit and lean, and then cognitively, you know, right? So, but that's a harder thing to measure, right? So at the top of the pyramid is leanness and fitness, right? But this has been the approach forever, right? Just eat real food and exercise. And everyone that's ever used that approach has died, right? So I'm not saying I'm going to be the first to break that mold, but there's got to be a deeper layer, a deeper layer, right? So this is going to be a long-winded answer. I hope I don't lose anyone. But anyway, it's important to get out there, right? So then if we look under the hood, right? Then let's look at just using blood biomarkers as an example, because there are things like blood pressure, so vascular health, lung function, how strong is your forced exhalation, just as one example, that are not included in blood biomarkers, but there are obvious important measures of organ and systemic health that get worse with aging, right? So that's also on the list. I don't want people to think, oh, it's only blood biomarkers. It's far from the truth, right? It's hierarchy at the top, and then subdividing into all of the biomarkers of as many organ systems as possible. So with that in mind, where to start, right? So blood would be a good representation of without taking tissue biopsies, right? I can't imagine any of us is going to go in eight times a year and pull muscle or pull liver. This is just unreasonable, right?

So then in terms of looking at a blood sample, about 45% of it is red blood cells, right? So obviously looking at red blood cell markers, whether it's total red blood cells, the size of red blood cells, which is the MCV, the variation in the size of the red blood cells, which is the RDW, which I'm sure you know, and maybe others may know, is an important predictor of longevity, at least in mice. And the data in humans matches the data in mice, which suggests it could be a marker of longevity in people too, a dramatically underrated marker of longevity. And then hemoglobin, right, which declines during aging, it's your oxygen carrying capacity. So all of those red blood cell measures would be basically second tier, where because it's such a huge fraction of blood and a major cell type, we want to be measuring those biomarkers. And then slightly above that are the white blood cells, right, at 1% of the total blood volume. So that doesn't mean that red blood cells are 45 times more important than white blood cells. It's just dissecting everything in blood and trying to measure the biggest trees in the forest, right? So white blood cells. But then white blood cells can be further subdivided. They don't all move in the same directions. So neutrophils and monocytes increase during aging. Lymphocytes decrease during aging. So we want to keep our eyes on those three because that's about 95% of total white blood cells. We want to keep an eye on those three over time. And it isn't just one time point. It's making sure that the neutrophils and monocytes aren't increasing and the lymphocytes aren't decreasing. All right. So now we got the cells and also platelets are in that list too. Right. So now we got the cells. We covered that in the blood. So now we've got the plasma fraction, right, where you've got proteins, metabolites, you know, and then so just starting with the proteins, right. So we could jump straight into things like cystatin C as a marker of kidney health or CRP, you know, inflammatory markers, CRP, IL-6, TNF-alpha. But the way I look at this is, I'm trying to go after the biggest trees in the forest. For me, it makes sense that optimizing the biggest trees would have the biggest impact long-term. So what are the biggest trees in the blood forest, right? So most of us are focused on glucose and lipids, lipoproteins, right? But just to put it into perspective, glucose is 80 milligrams per deciliter. Albumin is 4500 milligrams per deciliter, right? So albumin by far in terms of concentration is way more than glucose and even lipoproteins, right? If total cholesterol is say 200, 200 milligrams per deciliter versus 4500 milligrams per deciliter for albumin. So albumin for sure is a big tree in the forest that is almost always ignored or underrated, right? But then also, you've got the globulins, which can be subdivided too into IgG, which a recent paper showed is associated with longevity if you keep it relatively low. CR can reduce it, exercise can reduce it, parabiosis reduces it. Globulins can be up to 2500 to 3000 milligrams per deciliter. So again, putting that 2500 to 3000 versus the 80 for glucose or 200 for total cholesterol, globulins are a big tree. And then also looking at fibrinogen, right? So fibrinogen, 250 milligrams per deciliter, which again is three times higher around for glucose and then also higher than. So those are the biggest protein trees in the blood force. Now, does that mean things like cystatin C, which is 0.7 milligrams per liter or 70 micrograms per deciliter is less important? No, there are low abundance proteins in blood like CRP, cystatin C, TNF-alpha, IL-6, which are in microgram to even picogram. So 10 to the negative 6, 10 to the negative 12 in terms of grams, that are in very low abundance, can be very important for tracking during aging. So I'm not putting all of my eggs in the low abundance proteins. I'm looking at the big trees in the forest while also including some of the lower abundance stuff. And then last but not least are the metabolites, right? So technically glucose falls into that category. The lip lipoproteins fall into that category. Cholesterol is a metabolite. But then also looking at, you know, quote, unquote, novel cutting edge metabolites, kinuronin divided by tryptophan, EPA and DHA, which may be important for inflammation or a whole host of stuff. But even those metabolites, creatinine is a metabolite, right?