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Horvath Epigenetic Age: A Weak Spot, But I Have A Plan (14-Test Analysis)

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Resisting An Increased Epigenetic Speed Of Aging (14-Test Results)

Conquer Aging Or Die Trying!

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Papers referenced in the video:
Underlying features of epigenetic aging clocks in vivo and in vitro
onlinelibrary.wiley.com/doi/1...
Effect of long-term caloric restriction on DNA methylation measures of biological aging in healthy adults from the CALERIE trial
www.nature.com/articles/s4358...

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8 июн 2024

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Комментарии : 68

@jamesgilmore8192 Месяц назад

Bryan Johnson revealed that they think it was either a peptide or the follistatin gene therapy that dropped his DunedinPACE. In my opinion the follistatin gene therapy seemed more likely. Previously to this he said many of the longevity interventions they were trying were increasing his DunedinPACE.

@conqueragingordietrying1797 Месяц назад

Hopefully Bryan's tracking its impact on other biomarkers. It seems as if he's heavily weighing DP relative to other metrics, and I hope this isn't improve 1 biomarker, make others worse...

@jamesgilmore8192 Месяц назад

@@conqueragingordietrying1797 It's a shame he never mentions or publishes the other data.

@barrie888 Месяц назад

fascinating stuff with professional presentation, glad i stumbled on your channel Sir

@hristosstrihas4010 Месяц назад

Amazing!!

@jamesgilmore8192 Месяц назад

Mike -- tough situation. Some suggestions: 1) The omega 3 correlation is worth assessing with fish oil and/or flaxseed oil, very little downside it seems. 2) I would redo the analysis excluding the high-dose nicotinic acid point at 0.98. There is also the point at 0.89, but I don't know what was happening there (NMN?), but I'd try that as well to generate more ideas. 3) Treat the high-dose nicotinic acid point as a case study (and the 0.89?) and see what else changed from baseline both before and after in all your data. That should generate some hypothesis about what changes this for the negative and you can then work forwards. Perhaps make a video about it. 4) Would it be possible to label each point with the experiments you were conducting during each time frame? Maybe some patterns will show up. 5) Since these tests are reliant on blood spots it would be good to label any anomalies in RBC's and WC's, as some of the earlier clocks aren't robust against those changes.

@justsaying7065 Месяц назад

Good ideas. Yeah, I agree that the data point from nicotinic acid should be excluded since it's clearly an outlier. Also, I would analyze the three lowest data points (around 0.75 and lower; I'm just eyeballing the levels) and see what's special/different about those three.

@conqueragingordietrying1797 Месяц назад

Thanks James, these are great ideas. For #1, neither flax nor sardines is significantly correlated. I'll do #2, which is a definite statistical outlier that was caused by high-dose NA, which could provide more insight. I wouldn't exclude the 0.89, though, no interventions were being used for that. For #3, I can definitely label it, but for may tests, there were specific dietary interventions, which may include more than 1 variable. #5 is more tricky-that variability should be somewhat standardized form test-to-test.

@conqueragingordietrying1797 Месяц назад

@@justsaying7065 One was via NMN, but I didn't do a full blood panel on those days to see if other biomarkers were worse. I'm also not keen on supplementing with 2g of NMN/d...

@jamesgilmore8192 Месяц назад

@@conqueragingordietrying1797 With #1 I was thinking of moving away from whole foods. My only other thought was there are enough lean people on the epigenetic leaderboard to suggest that CR is probably important, although there seems to be a limit. This might suggest making a fixed adjustment/regression for calorie intake to DunedinPACE giving a deviation, and looking at correlations with "DunedinPACE deviations", rather than correlating the actual data or making calorie adjustments for each variable would be worth trialling.

@maestroharmony343 Месяц назад

When I was taking 500 mg Niacin, my DP was the worst of all. Then, when I wasn't taking any B3-related supplements, DP got significantly better. Also I tried taking 1000 mg NMN and DP test was not as bad as with NA. Now I was taking 100 mg NA again and just did the test. I'll see.

@chris-lk4ml Месяц назад

Maybe you'll find some correlations with sports and your favorite type of relaxarion methods

@djblame8954 Месяц назад

Awesome video! In addition to brocolli sprouts what sprouts do you recommend for anti aging?

@conqueragingordietrying1797 Месяц назад

Thanks @djblame8954. Alfalfa sprouts are in my current approach, too, but I think the best approach includes sprouts that are specific to one's biomarker needs...

@j.c.higginbotham6401 Месяц назад

Radish Sprouts has sulforaphENE, which seems to have its own benefit when compared to Brocolli sulforaphANE

@adamd9418 Месяц назад

Thanks for an informative video as usual. It's surprising that there isn't anything specifically in your diet that correlated to the Dunedin pace of aging. Although it appears that the # of calories does.

@conqueragingordietrying1797 Месяц назад

Thanks @adamd9418. Although calorie intake was significantly correlated with DP after earlier tests, it's not currently significantly correlated.

@Nof1LongevityQuest Месяц назад

I'm still struggling to understand Caloric Restriction. Let's say I am a 56yo female weighing 109 lbs with a BMR of 1300 calories per day and another 500 calories burned during running and daily movement. So theoretically, if I ate 1800 calories each day, I would stay at exactly the same weight and that would qualify as zero caloric restriction. It seems that if I ate 12% less than this, my weight would continually decrease in very slight increments. If 109 is already my goal, how is caloric restriction good for me? Maybe I just still don't understand the concept.

@Nof1LongevityQuest Месяц назад

I would love to see a video on the number of calories you consume and burn each day and what effect that had on your daily weight.

@conqueragingordietrying1797 Месяц назад

Hi Gail, my understanding is that CR is defined based on a restricted intake relative to ad lib intake. For example, since 2015 my highest average intake that corresponds to a blood test is 2800, and my current intake is around 2100, which is a 25% restriction. I'm not sure how many calories that I burn, as WHOOP's metric for that isn't accurate (I'd gain weight based on their equation, not lose over the past3y). But, I know how many calories that it takes to maintain BW, as I weigh all my food in conjunction with daily weighing.

@Nof1LongevityQuest Месяц назад

@@conqueragingordietrying1797 Thanks for this. I do believe Garmin is fairly accurate in measuring calorie burn, and I have dialed it in so that I can keep my weight much more stable than I used to. I've been measuring my food, like you, since May 1 of this year. It's sort of challenging at this low body weight and caloric need to hit all the nutrient targets. That definitely keeps me eating only unprocessed foods. I guess, for me, caloric restriction is meaningless since I definitely don't eat any additional calories other than what is needed to fuel me and keep weight within +/- 2 lbs.

@ChessMasterNate Месяц назад

I would assume reducing calories would also reduce your weight until there is a match between that consumed and that burned.

@jamesgilmore8192 Месяц назад

You need to differentiate between what your goal is (109) and what biomarkers related to longevity say. At your weight the obvious risk is low bone mass as you age, and say you had a strong family history of hip fracture, you could argue that 109 is too low and therefore you are too restricted already and need to do resistance training. So its complex, and its not simply about CR, the biomarkers related to longevity need to be considered.

@YuraL88 Месяц назад

There are 2 obvious outliers at 3:07, one of them is even close to 1. Do you have any idea/hypothesis what might have caused them?

@conqueragingordietrying1797 Месяц назад

Yep, high-dose nicotinic acid (600 mg/d) for the 0.98 point. I'm not sure about the other (0.89). Covered in this video: ru-vid.com/video/%D0%B2%D0%B8%D0%B4%D0%B5%D0%BE-NvzTCiaAYZo.html

@YuraL88 Месяц назад

@@conqueragingordietrying1797 thanks.

@costa768 Месяц назад

@@conqueragingordietrying1797 This paper can give insights into why "The acute effect of different NAD+ precursors included in the combined metabolic activators" Also a p value is also higher than 0.05 is also significant "Are Only p-Values Less Than 0.05 Significant? A p-Value Greater Than 0.05 Is Also Significant!" Also omega 3 is negatively correlated?

@ChessMasterNate Месяц назад

Have you considered combining all the different kinds of epigenetic tests together that you do, looking for correlations with foods? Quick and dirty would just be averaging all the correlations for each food, but now with a larger number of tests, significance may be achieved.

@conqueragingordietrying1797 Месяц назад

The epigenetic tests have different strengths-for example, while Horvath is the best predictor of chronological age, it's not for ACM risk.Conversely, DunedinPACE is among the best for ACM risk but is not strongly correlated with chronological age. So combining these tests into epigenetic aging metric aisn't the best option, imo

@ChessMasterNate Месяц назад

@@conqueragingordietrying1797 Each of these looks at a very small subset of methylation points, so there is not likely to be a lot of overlap, which would be the main concern in combining them, I would think. Each, though, is methylation, and each is designed to measure aging. And I would assume whatever improved future tests are developed that are superior would look at more methylation sites to achieve greater accuracy. Combining tests gives you a sneak peek at what a more advanced test might show, and you can use all these data points collected, rather than waiting 3 more years of testing to have as many data points to work with for each individually. Each of the methylation points chosen likely corresponds with things likely to change on a typical Western diet and lifestyle. A bigger net is probably more useful if your diet and lifestyle is atypical. I would think.

@jamesgilmore8192 Месяц назад

@@conqueragingordietrying1797 Yes Mike is correct. You shouldn't combine the tests when looking at/for factors that influence the tests. They all use different cohorts, statistical approaches, end points, etc and they need to be examined individually.

@newdata Месяц назад

can double check w total calories/protean vs the test result

@conqueragingordietrying1797 Месяц назад

Yep, both aren't significantly correlated with DunedinPACE

@jamesgilmore8192 Месяц назад

Celtics or Mavs Mike?

@conqueragingordietrying1797 Месяц назад

Ha, I divorced all my sports teams a long time ago, so I don't have any skin in the game, but it's highly probable that the Celtics win this series

@justsaying7065 Месяц назад

What happened to your hypothesis that LDL is negatively correlated with DunedinPace? (I’m doubtful about this hypothesis.) I believe you increased saturated fat and cholesterol intake to raise LDL to test the hypothesis.

@conqueragingordietrying1797 Месяц назад

Hi @justsaying7065, apologies, I should've gone into that at the end of this video... For 2 tests, I indeed increased SFA and/or dietary cholesterol with the goal of increasing LDL to test its DP correlation, and although LDL was on the high side of my recent range (82, 83 mg/dL), it wasn't beyond my normal range, which may have failed to reduce DP (assuming that LDL is causative in this equation, which may not be true). Additionally, these dietary changes may have made other biomarkers worse (kidney function, Horvath, as examples). So for now, I've paused the LDL-DP experiment, even though they're still significantly correlated.

@justsaying7065 Месяц назад

No worries. Thanks for the update.

@jamesgilmore8192 Месяц назад

@@conqueragingordietrying1797 Disappointing but maybe not unexpected. Perhaps the association is related to the receptor or some other mechanism in the general population.

@darrenparis8314 Месяц назад

The DunedinPACE does not correlate with your diet components - OK What about other factors? Did you find any?

@conqueragingordietrying1797 Месяц назад

I looked at body weight and calorie intake, but nothing significant there, either

@darrenparis8314 Месяц назад

@@conqueragingordietrying1797 what about cortisol?

@dirkheyer6871 Месяц назад

Vitamin D, Magnesia, Carotinoids, Lifestyle and Sports should be also important for methylation. I know there is a study about Vitamin D and methylation, maybe done in 2022.🤔 ...and for Vitamin D is Magnesia/K2 an important faktor, maybe also Gut Bacteria, with some you get older and they can be a pre faktor for DNA methylation.

@conqueragingordietrying1797 Месяц назад

Thanks @dirkheyer6871. I could go higher for Vitamin D, Magnesium is already ~2x the RDA, carotenoid intake is high. Gut bacteria should be close-to optimized with 85g of fiber/d

@dirkheyer6871 Месяц назад

@@conqueragingordietrying1797 I have seen a Diagramm that Vitamin D influences the DNA repairing positive, maybe positive on DNA methylation. Maybe Fiber intake is only one Part, there are Gut bacteria who like apple vinegar or Milk products, maybe other things and more than Fiber. There are also studies about different Gut bacteria as Supplement, which are better for Sport or Longevity etc. Maybe you are testing different Gut bacteria later.

@PaulBeauchemin Месяц назад

Time for rapamycin

@conqueragingordietrying1797 Месяц назад

I'm open to it-I'm currently tracking Candida IgG, which is higher than it should be, and rapa is well known to kill Candida. But, I've been able to reduce Candida from a high of 1.2 to 1.0 for the last test, so I might not need rapa. But if I get stuck, short-term rapa is definitely an option.

@monnoo8221 Месяц назад

was't grimage showing the best association with ACM? In my opinion, hose age clocks need to be related to a wide vector of physiological markers, and to health events like cancer, or CVD, in a cohort that has not chronic disease and a healthy body composition. Using ACM is already integrating the treatment aspect and should not be used as endpoint. Those aging clocs are all based on a weak theory, IMO, which s why they use chronological age on both side of the equation.... I think the proper approach would be to have as much classical markes as possible arranged in a vector / profile, and then determining the (non-euclidean) distance of your data to a youthful condition. That distance you could track over time. it would make much more sense than those fancy marketing tools.

@conqueragingordietrying1797 Месяц назад

DunedinPACE and DNAmPhenoAge are in the same ballpark as GrimAge for ACM risk Agree on classical markers

@MikeG-js1jt Месяц назад

its $500 .............. how the hell are you spending this much money on all this testing, I understand some of us have more than others, but sheesh! to spend it on this so often seems a little ridiculous.

@conqueragingordietrying1797 Месяц назад

I disagree-I see it as an investment in a potentially longer life. Others can disagree, no worries

@a_bar8579 Месяц назад

Unfortunately, you are ignorant and do not know how much effort this work is worth!

@joebartles3986 Месяц назад

I assume he can buy the tests at a reduced cost and/or he gets a commission on the people who buy this test using his discount code…

@aquamarine99911 Месяц назад

Hah, I've got four electric basses, two electric guitars, three amplifiers, two 88-key pianos (one electric, one regular), two synthesizers, a rack mount Mellotron (!) and another tone generator. And I'm not even a professional musician. Seems a little ridiculous, right? My wife certainly thinks so. This is Michael's passion, and it can potentially help all of us. I just finished reading the "The Discoverers", an excellent book. Normal people making financially rational decisions didn't help to advance civilization to where it is now.

@monnoo8221 Месяц назад

@@aquamarine99911 absolutely true. I for myself also took a lot of risk, and did not get paid out in the end. As with all discoverers, some are too early, and such for any successful we should not forget about those who tried and failed in some way

@whatthefunction9140 Месяц назад

............................................................................................................................................................................. Hello there

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