Epigenetic Tests #1 and 2: Horvath, Hannum, DunedinPACE
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- Опубліковано 14 жов 2024
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Papers referenced in the video:
Underlying features of epigenetic aging clocks in vivo and in vitro
pubmed.ncbi.nl...
DNA methylation‐based measures of biological age: meta‐analysis predicting time to death
pubmed.ncbi.nl...
Decreased epigenetic age of PBMCs from Italian semi-supercentenarians and their offspring
pubmed.ncbi.nl...
DunedinPACE, a DNA methylation biomarker of the pace of aging
pubmed.ncbi.nl...
Effect of Long-Term Caloric Restriction on DNA Methylation Measures of BiologicalAging in Healthy Adults: CALERIE™ Trial Analysis
www.medrxiv.or...
By FAR channel with the best content on longevity. Again looking forward to the video!
You got me man! I'm becoming your Patreon supporter today! This channel is really the best anti-aging channel out there. Thanks a lot!
Thanks for all the learnings and sharing this with the community!
Thanks Gokhan, and thanks for the support!
Excellent results 👍. You have the most relevant and reliable numbers. Keep up your wonderful work. You are the one!
Thanks Ket TOO! If I can keep it going for the next 74y+, then maybe I am the one!
@@conqueragingordietrying123 Yes You are the one! You're most welcome.
Fascinating so much to ponder and discuss here
WOW! That was an incredible video, Dr.
Will you show GrimAge in the next video?
I didn't know that GrimAge showed no statistically significant effect of calorie restriction in humans!
I believe that DunedinPACE shows the current aging rate (that's why it can be lowered quickly with short-term interventions).
In contrast, GrimAge shows an aging snapshot of all the aging accumulated over a lifetime.
I speculate that's the reason why GrimAge couldn't find an effect of a 24 month CR.
Cool info
I've noticed something that doesn't make sense about the clocks in the CALERIE Trial. In the Ad Libitum group, we expect to see 1 year increase in biological aging at 12 months and 2 years increase at 24 months. But that's not what we see for most clocks. Only Hannum and GrimAge are trending toward these expected patterns, while DunedinPACE shows a 1 year increase in biological aging in the AD group at 24 months. Horvath clock which has the highest correlation with chronological age, shows about twice the increase at 24 months compared to 12 months (makes sense) but at 24 months, it shows only 1 biological year has passed (doesn't make sense). To conclude, something is fishy about DunedinPACE in that data.
For all the clocks except the Dunedin's, epigenetic age increased in the AL group up to 2y during the 2-yr intervention. But, I get your point-both Dunedin clocks don't show that at the 2-yr time point for AL. We need more studies, more data to sort it out! Ha, battle of the epigenetic clocks.
Looking forward to seeing this. :)
Very Interesting ! Thanks. Using DunedinPace for example, can you drill down to see which gene expression can be tweaked for better results? Also, wondering of Levine's DNAmPhenoage tracks consistently with any of these tests? for instance if you improve on Levine's Phenoage, is there a proportionate impprovment in DunedinPace? Will have to do some more homework to better understand these tests and why the first test was such an outlier.
Thanks Peter. TruDiagnostic provides the full CpG methylation data, so I'll have to take a look.
I have corresponding PhenoAge data only for the 7/11 test (blood draw around the same time, 730 AM), and it was 32.6y, which tracks with Hannum and DunedinPace, but not Horvath.
In terms of improving the possible connection between PhenoAge-epigenetic data, stay tuned-I plan on testing with TruDiagnostic multiple times, and each with corresponding blood testing to calculate PhenoAge and aging.ai.
This is exciting. the phenotypical age calculators meet epigenetic clocks!s
You're right. This is exciting.
My Horvath was 4 years older as well and phenotypic based on markers 12 years younger.
Great video again to stimulate debate about optimal longetivity. So maybe i was wrong about the brocoli and its benefits. Hahaha. Thanks for sharing your data. At least your are transparent sharing the positive and negative about the different methodologies about aging. I am confused about the results about the epi clocks which have a low HR. If your HR below 2, you can have a statistical significance. That is what i have learned. Over time we will get to better define what is better for each person. In the meantime, i continue to xecute on resistance and more on cardio so that i have a higher Vo2 max>HRV>RHR. I am not targeting to live at >120 but rather to beat the one hour bike speed record for people >100 yr old at 27km. Hahaha
Thanks ccamire. Note that when the 95% confidence interval is either completely above or below 1, then we have statistical significance.
You finally did a methylation! I bit surprised how these test have different numbers. Is any way to change the Horvath number?
Ha, yep Olya! I'm not sure, but I'm planning on retesting, so we'll find out!
I have 4 FOXO3 all homozygous for increase lifespan. Most of my great grandparents and grandparents lived between 97-106. They didn't do anything different among the populations they lived with.
That's great, TheShumoby. Have you tested your Horvath age? I'd bet that it's a lot younger than mine.
What test did you do to get this information?
@@conqueragingordietrying123 No, I haven't done the Horvah test. I'm 45, but I still get carded at bars. People say I look like I'm in early 20s.
@@realanli I downloaded my raw data from 23andme to foundmyfitness.
@@TheShumoby thanks 🙏
Michael, how accurate and repeatable are the labs that perform the epigenetic testing such as Horvath?
Horvath and DunedinPACE are well-researched clocks (i.e. published, peer-reviewed), so I'm not concerned about TruDiagnostic measuring them. That's in contrast with other epigenetic clocks (or other biological age clocks) that have no publications (I can name names, but won't!).
Congratulations! Is the TruDiagnostic data suitable for use in Dr. Horvath's online GrimAge calculator? It doesn't say GrimAge on that page, but studies such as "Does the epigenetic clock GrimAge predict mortality independent of genetic influences: an 18 year follow-up study in older female twin pairs" state that it's available there.
Thanks Paul. DunedinPACE is a different test than Horvath's, so I don't think that works. There's evidence that DunedinPACE may be better than GrimAge, that's at the end of the video.
@@conqueragingordietrying123 Okay, I asked the company and will update here with their reply. Dunedin is a good cohort for you as they have the same birth year and ancestry. Think there's more work to be done to show that measuring pace of aging is better than measuring the total progress of aging, and that its test-retest results are reliable.
@@paulrice147 Definitely-also note that test-retest data is their related paper is in the video's description, and it was pretty good.
Anecdotally, test-retest for me was 0.8 and 0.82 in tests 6-weeks apart, which is also reliable.
@@conqueragingordietrying123 From TruDiagnostic: Thanks for reaching out. Yes, the raw data should be suitable to use for calculating GrimAge. However, the IDAT files will need to be processed to generate beta values (which I believe is the input). This should not be too much trouble to convert to beta values however using a pipeline such as minfi.
We can also provide beta values.
@@paulrice147 Ah, my mistake, that's great!
Can you help me understand the chart provided for the CR on the DunedinPACE? It says change in DunedinPACE and it's like -1 for CR and +1 for AL. I don't get what that means. It can't surely mean the DP value went from like 1.6 to 0.6?
Sure N330AA, no worries. From Figure 2 in that paper, " change scores are denominated in Pace of Aging units
scaled to be interpretable as percent difference in the rate of aging relative to the reference norm of one
year of biological decline per calendar year."
@@conqueragingordietrying123 Oh boy, now i'm even more confused. So CR reduced pace of aging by 1%?
@@N330AAI don't think it's 1%-because DunedinPACE is a pace of aging measure, and not an absolute age, they scaled their data in easy into understand units, i.e. +1, -1
I appreciate all of your hard work Michael, thank you.
DunedinPace and GrimAge might be the best measurement options for now and GrimAge isn't available so that leaves DunedinPace. Now if DunedinPace happens to correlate with the phenoage spreadsheet we would have a cheaper way to periodically check because the necessary blood tests are less than half the cost of the Dunedin test.
I agree that yours is the best approach currently available to slow biological aging and I do the same thing but I wonder if it is truly accurate to say that we have slowed it? I took a screenshot of you when you did the Michael Rose interview and put your image into one of the online photographic AI age estimators and it calculated your age at 49 when you were 48. So are you, me or anyone else really "biologically younger"? I am wondering if all we really are doing is reducing our future time in poor health, which is a worthwhile outcome itself.
Hi Lee, I appreciate the constructive criticism, but you're assuming that photoaging-based clocks are as good as blood-based biomarker or eipgenetic clocks-I haven't seen any published studies making those comparisons.
That said, my experience with the photoaging clocks is that they can be manipulated with good lighting, for example, and I'd bet that taking screenshots of me in videos wouldn't be ideal.
Ha, people should take their shirt off and then a photoage should be calculated-with the shirt on, people can hide their physical limitations.
Nonetheless, I'm always adding to this approach with the intention of continuous improvement, so let's see whether I look younger or older over the next few years.
@@conqueragingordietrying123 I am sorry it sounded like criticism because it isn't. You are doing a fantastic job. My poorly worded point is merely that I am not sure what to believe when all these clocks claim great correlation yet they all give a different result. To me it means none of them can be trusted yet. But with regard to "biological age" IMO to be considered to have a younger biological age than calendar age EVERY aspect of the person needs to be indistinguishable from a person of that younger age.
👍
Do you know if GrimAge is available commercially? I am far more interested in predicting all-cause mortality risk than calendar age.
No
@@joachimdrtuerk Thank you for your response. I haven’t seen it and was wondering. The tests covered here do offer good alternatives.
@@christopherbrand5360 There's data in the video that DunedinPACE may be better than GrimAge.
@@conqueragingordietrying123 I was reacting to the hazard plots for the two studies, where it looked like GrimAge looked stronger (at least trending stronger). I did have some distractions while playing the video and should go back and re-watch. Thanks!
@@conqueragingordietrying123 DunedinPACE is definitely attractive as a potential add to blood bio marker testing
OMG FINALLY
lol Alex
Do essentially all women have a biological age which is 5 years younger than their chronological age? (Because they tend to live 5 years longer than men). Or would their biological age just have a different scale than a man's?
I see the logic, but I'm not sure if it's true. Maybe they have a slower aging rate, too?
@@conqueragingordietrying123 The phenotypical age calc doesn't ask if you are male or female correct? So it would be interesting to know if what I said initially is how that slower age rate would express itself in the calc.
@@surfreadjumpsleep You could ask Morgan Levine, she's on Twitter and generally responsive...
@@conqueragingordietrying123 OK I just did and tagged you too. Yeah that's a twitter burner account. Twitter kept kicking me off for being angry with Russia this spring.
I read that women have longer telomeres - they evolved to help out with child rearing by advising younger women, whereas older men are not so useful.
I wonder if your methylation age is not due to the fact that you've been taking a B12 supplement for many years I believe. B6-B9-B12 supplements has been shown to accelerate methylation aging. I probably have the same problem, given that I have taken multivitamins for most of my life, and even B6-9-12 supplements for about 6-7 years. I take CaAKG now, hopefully it helps.
Your methylation seems to be your weak point, perhaps it would make sense to try and concentrate on that rather than on your biological age based on blood markers?
I stopped taking B12 in early March, which is ~3 months before the 1st epigenetic test, so I doubt that's the case...
@@conqueragingordietrying123 Maybe that's why your Dunedine test shows slow methylation aging of 0.8. But for many years you may have been above 1 because of the B12. You've accumulated all that DNA methylation over the years, and it's hard to demethylate now.