Hernandez Paul Gonzalez Angela Davis Sarah

I just watched a 3 year old video of yours and now this and I gotta say, based on that one video from 3 years ago, how you talk (fluidity, errors,...) has improved so much, really great stuff. Also, yet another fascinating video...I'm usually just constantly smiling when looking at all that data and science and how crazy complex the body is. Thanks!

It's fascinating...there's so many foods with a variety of potentially benefitial compounds. You read about blueberries and kale, but then you have stuff that's not so common and you discover that these also contain potentially benefitial compounds. I'm almost thinking that one reason of why some foods are deemed so healthy is because of the amount of research that is put into those, which may be influenced by how well they can be sold and/or produced.

Can you make a video correlating your BMI index with your other biomarkers? Your BMI seems like it would be a far more significant variable than many of the things you have been looking at (like particular foods).

Why are we not using mean lifespan instead of median lifespan? It would be a more robust way to compare results

If we accept hi claim that using mouse data the maximum lifespan of humans is 90 years then it is common in some sub-populations for them to live 10 to 15% longer but so far there are no clear reasons why except reduce mitochondrial numbers and function, reduced telomere length, lack of naïve T cells and pluripotent stem cells.

semi-on topic for the video but: regarding relative risk reduction (and formulation of a "mathematical" (of sorts) formular for longevity science) in respect of (for example) "relative risk" or reduced mortality risk: often studies show relative reduction of reduction in mortality, but that makes it hard to figure out the magnitude "in the grand scope of things" of the different interventions and how they impact micromorts/microlives - technically this (initially) isnt as relevant (as long as a field is in its infancy, which longevity science might as well be considered to be) however: at some point it will not become important "which things u add to ur life or avoid" (because they r promissing/detrimental) but instead which ones r the most effective/efficient (resource/time-wise) overall. for example walking 8800 steps might be kinda nice (for longevity) but if it takes >1h to do (and if it wasnt compatible with other longevity stuff that u can do simultanously) then walking might be pretty F-tier so to say so tl;dr: yea maybe some big brain can come up with a way to converting relative risk reduction into micromorts(or in that case: microlives) for studies :P (need minimum 120 iq or ai help to understand this convoluted mess i just wrote, sorry)

another great video

do you eat the sardines straight out of the can or do you fry them? microwave them?

To correct rate the biological longevity of people, you have to check older people after 60 years old only. Because younger people often die not because of biological problems but because of drugs, bud habits and other mechanical reasons. (Hi from Siberia!)

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57:00 Really wish to know more about things affecting DNA repair greatly in actual humans. The last time I looked I stuck with: MSM reducing DNA repair capacity, but was somehow greatly beneficial regarding association with colon cancer. Kiwi, large doses of Vitamin C, green tea and Cat's Claw extract increased DNA repair, but weren't that great for cancer.

Great questions

Good guest

What about thymus regeneration, a la Greg Fahy?

I don't get the argument, perhaps, but he presented one is kind of seriously incomplete. I get the statistical argument, what I refute is the framing of it. An organism achieving high age is certainly more resilient han one that is dying early, such it would respond less to any disturbance. Applying a whole range of interventions and always ending up with a certain max age does certainly NOT indicate a species specific barrier. It is only a limit for a given set of theories, practices, and configurations. so, so what, if the animal that would live longer anyway, up the the currently avalable empiric limit, does not respond??? Vice versa, assuming that there is an inherent max life span, increasing life, healthspan for for otherwise short lived animals is exactly what we want to achieve, do we? Regarding mice, but also for other higher animals, it is extremely important to be aware about the cause of their deaths. In mice, it is lymphoma for 90%%+ of cases, something that is very rare for humans. We die from a disabled immune system and the attacks of bugs, if we did not manage to kill ourselves through bad habits (misguided experimentation). This applies to especially to the interention of calorie restriction, as cancer is dependent on nutrient availability. Such, looking for long lived controls is definitely not the solution. Instead, an animal model has to be created which reflects perfecly the same causes of death as we face as humans. Only then we can draw conclusions. Whether those are long lived or not, does not matter at all. What would matter, however, would be a proper physiological description of the organisms, much like what michael is doing with himself. Without that: simply bad 19th century science. IPS. forget it. How culd youo replicate an experiment 8 times at 2 lab locations, all with small samples, and the lump them ? That's not bad science, that's science informed by ideology.

It should also have been mentioned that mice die primarily from cancer, humans primarily from cardiovascular diseases. What extends a mouse lifespan is essentially something that delays cancer development.

How do you use the information from his answer 49:30 onwards? In short how you have selected which biomarkers you want to keep at youthfull levels? That is what I am missing with your aproach.

Very good presentation and discussion. Thanks! The AKT-2 inhibition on one graph is interesting (at 17 min). If memory serves, cruciferous vegetables inhibit the PI3k-AKT2 pathway. Would be good to do a critique of the ITP process at some point. One issue is that their intervention doses are often not realistic for human consumption (way too high) and they do not provide human equivalent doses (very important for context) in their papers. Same applies to many studies other than ITP. On CR vs Fasting and protein restriction, the Lamming Lab has done some interesting recent work, appear to show that Fasting does a lot of what CR is credited for, but also that the overlap in gene expression changes is not 100%. Based on this mild DR combined with TRE might be the way to go. They also showed that isoleucine restriction might be worth further life extension studies.

Timestamps: 0:00 Intro 0:30 Paper Presentation 25:32 Q&A-Maximum Lifespan Assessment? 26:32 Sample Size In Longevity Studies 27:56 Disparity For CR Studies In Terms Of Background Genetics 29:00 20% vs 40% CR Included In The Analysis? 29:50 CR + Fasting + Circadian Alignment 31:52: Diet 33:00 Protein/Methionine Restriction 33:57 Keto 35:02 Would Supplements That Extend Lifespan In Short-Lived Controls Have More Benefit In An Unhealthy Human Population? 37:50 Using Biomarkers To Guide Whether Longevity Compounds May Be Beneficial 40:15 Does Rapamycin Work In People? 43:22 Healthy Fatness Longevity Impact? 45:15 How Has Your Research Impacted Your Personal Supplementation Approach? 46;28 Supplemental Intake vs Circulating Levels 49:10 Shifting The Circulating Metabolome Towards A Youthful State 51:20 What's Next For Kamil 53:05 Chemical vs Non-Chemical Interventions 54:18 What's The Aging Community Slow To Study? 55:19 Under-Appreciated Longevity Approaches 56:12 Combination Therapies For Lifespan Extension

So you don't have any other dietary substance that correlates inversely with these gut microbiome byproducts and yet does nothing adverse anywhere else? I think you should look for such substances and leave the coconut butter where it is.

Because your IS and PCS have increased in your last 11 tests, it would seem you could loo at your diet changes that you make before each test and derive the information on the effects of coconut oil or other nutrients that are suspected of raising the metabolites. For IS, tests 4, 6, 10, nd 11 it substantially raised. For PCS, tests 2, 3,, 5, and 6, substantially raised. Look at test No. 8. Woohoo excellent result. What did you consume for those results. Perhaps you can leave coconut oil out of the mix and concentrate on other nutrients first. Telomere length is a critical factor to keep as long as possible. I think. And one last thought: what is the repeatability of the Iollo tests? How do you know the results are not within some wide margin of error?

What's your CRP after this diet?

Whoa whoa. Broccoli is correlated with an INCREASE?? Why could this be?

The actual life expectancy differences in years is interesting to point out. I do wonder what the effect of obesity was on that, since as you guys mention they didn't provide values adjusted for BMI. I've only watched a few Attia videos on VO2 Max, but I don't think he goes overboard with regards to training solely to maximize VO2 Max? I think he himself does mostly Zone 2 cardio, with a session or 2 a week of 4x4 type interval training for VO2 Max. That doesn't seem like overtraining for VO2 Max to me. Of course, all of your general points are well taken about overall health and healthy practices/lifestyle.

Association with flexibility- may be a healthy user bias, for example: ppl who take care of their health exercise and stretch… so maybe its not the state of flexibility by itself

idk if u already covered it (maybe indirectly - thru means of bmi) but: do u have (in ur never ending data stream 😂) info on how basic bodily metrics impact life expectancy? i mean stuff the average scale displays - namely: weight (bmi), water percent (more = better? up until like maybe 75%?), fat percent (j shaped?), muscle percent (the more the better (up to a certain point)?), bone percent (the more the better?) ? 🤔 and how to impact them (for some its obvious, but i guess eating more salt to get higher water retention isnt the way to go for body water percentage 😂)

Is there any special reason for you to eat macadamia? They don't play a role in my diet. My nut intake is already above 70g/day

This was very informative to me. - Are there interspecific differences between different kinds of mushrooms or any kind of edible mushroom should negatively correlate with these metabolites? - Are there reasons to believe that supplementing with pantethine instead of consuming B5 from food of supplements will also negatively correlate with these metabolites given that higher levels of pantethine correspond to higher levels of B5? - Is kefir expected to positively correlate with both of these metabolites or at least with indoxyl suflate?

Hi Michael I have noticed you are a big consumer of strawberry I was wondering the "idea" behind? Fisetin?

dont oyster mushrooms have much more ergothioneine than other mushroom types?

there are much higher mortality for other derivataves of tyrosine and tryptophan in the diagram

Lopez Jose Gonzalez Gary Anderson Charles

possibly its like so: satfat (generally speaking)= bad for telomeres (thats somewhat basic vegan knowledge) but - lauric acid (the main (saturated)fatty acid of coconuts) messes with the gut bacteria (u mentioned at 0:29) that convert the 2 aminos into shitty metabolites (yea i know the data u displayed didnt include "satfat" so i could technically conclude that there is no such association but who knows) u could try swap out the coconut for C12 sattyfatty MCT oil (if that exists?) and see if some interesting new associations pop up - or alternatively if there is an alternative to mess with those sucky bacteria that convert the aminos

What happens if you combine high levels of mushrooms and Coconut butter?

amazing video. I started doing the 800 gram lifestyle by EC Synkowski and it has changed my life.

The adventure hits a fork in the road!

Honest comment. You have gone way too far into the weeds. The tools you are using to measure then adjust are just not that precise or accurate. But I do enjoy your videos.

not a conundrum. just ignore coconut butter all together and focus on other factors. 6/24 data should be scrutinized more closely as an outlier and possibly be removed. perhaps there was a latent viral infection or something else going on.

So does that mean that higher intake of tryptophan could potentially lower albumin levels?

Beef increases telomere length. How about beef fat

Have you made any efforts into weighting different correlations? Like maybe a certain food raises your glucose but lowers your homocysteine, how would you weight which one affects your longevity and/or healthspan more?

Conundrum indeed

I think coconut butter can stimulate bile secretion, and bile acids are known to augment our microbiome. But this mechanism contradicts to nuts consumption negative correlations. Maybe these nuts contain some components that stimulate bacteria overgrowth.

The second to last test around 6/24 seems like an outlier in my opinion. Does the entire analysis change if that is removed? It would have a large "influence" on the analysis, you could calculate a cooks distance to quantify it.

If the coconut butter correlation stands, you can try different coconut products like coconut oil or coconut flour. And you may also go more granular later, like mct or other components of coconuts. As for the mushrooms, have you thought about changing the species? I don't think mushrooms should be treated as one single thing, they are as diverse or more than plants and their nutritional profiles vary a lot. I just found that lentinus edodes (Shiitake) has half the niacin pleurotus ostreatus (Oyster mushroom) has doi: 10.1021/jf001525d. Of course sadly most species are not available in the supermarket and some that are can be quite expensive if they are will caught, but a few of them are.

now, with those seemingly contradictive pieces of evidence it gets interesting ;) First, about the metabolites: indoxyl and -cresol are highly correlated with LPS. Is that included in IOLLO? should be... They are also correlated wth bad gut bacteria. not all of them create indoxyl and p-cresol. Maybe, in your case, that aspect is the dominant one. What also caught my eye was beta-carotene. In your case, since you feed them raw, beta-carotene may also be a marker for a certain type of gut microbiome, since carrots, like other veggies growing close to the soil surface, or even in it, are populated with a wide range of not so friendly bacteria. Second, about the seemingly contradictive pieces of evidence. This is clearly a consequence of your monovariate approach. Yet, even a multi-variate statistical approach will yield the same contradictions. At your level of empirical sophistication, you need a completely different empirical approach. (about homocysteine we talk later when you will show the mushroom effect in one of your next videos)