DNA methylation test

myDNAge has a $299 urine or blood test for DNA methylation, they're running a buy get one 50% off at the moment. Steve Perry recommends this company, I ordered a test and will let you know how it goes. I'm using the spread sheet that JGC  created on this excellent thread for comparison. I'm expecting they should agree +- 3 years, if not I'd suspect the Levine paper results. 

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  • Hi Dan. No rush but just wonder if you got results. Sorry if I overlooked them in case you posted in another thread. BTW, I wish to congratulate for your activity in this Forum and your posts. Best wishes for the new year and keep up the great work 😀

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      • Danmoderator
      • skipping my funeral
      • dantheman
      • 1 yr ago
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      albedo No problem, but no I haven't gotten it yet. Takes a number of weeks, plus we have the holidays. 

      Thanks for the kind words otherwise. 

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  • Hi Dan. Do you know how many CpG sites the DNAage probes? The original Horvath's clock uses 353 sites while the "new" one (Levine's 2018) aka DNAm PhenoAge uses 513.The two only partially overlap.

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      • Danmoderator
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      • dantheman
      • 1 yr ago
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      albedo No I don't know what exactly they're testing, here is what they say

       

      The myDNAge® Epigenetic Aging Clock service is based on Steve Horvath’s aging clock and utilizes SWARM™ (Simplified Whole-panel Amplification Reaction Method) technology to analyze DNA methylation patterns of >500 genetic loci and provide epigenetic age predictions in a high throughput manner.

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  • <moved>

    I got the results of my test back, 48 +-3, and I'm 52. This was done as a baseline before I did NAD patches and started Metformin, but is with a life of healthy living (exercise and whole foods vegan, plus fasting the last five or ten). Disappointing, but it also said I was in the 91% percentile, meaning that I'm younger than 91% of their customers who are also at my age.

    A little surprising, I expected a lower measured biological age and a lower % as their customers (I assume that people testing for this would be a healthy lot). I also wonder how my reported age is used here. From the papers I'd expect it to be a pure measurement, but oftentimes with these kinds of things they'll normalize it for your age (a technique I've never been happy about).  

    For comparison the calculators gave me IIRC something like 35 and 45 calculatedbiological age. One of them at least was within the error bars of measured. 

     

    {reply from  albedo  }

    Thank you for sharing. 

    It would be interesting to repeat also after your metformin/NAD trial.  However, I feel today there is too much heterogeneity between the different methodologies to determine biological age and almost daily we get a new paper with a new calculator. DNA methylation looks to be a kind a standard that is imposing itself though. Your value is still positive though despite the error and despite I understand you were expecting much better.  I am trying to arrange this also for myself and maybe I will learn more to tell you in response. 

    I do not understand well the normalization process they seem to make. What does it mean? If normalization is to your age, then probably this hints to look longitudinally to a trend as I always thought, independently on the methodology? I tend to agree with you now: it looks like a relative measurement not an absolute one. And then we have, I guess, the unresolved issue of DNAm correlation vs causation of aging. Age is included in many of the calculators, e.g. the Levine's Phenotypic Age we discussed, but for the latter the reason was to convert the regression to a "year" measurement, IIRC.

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      • Danmoderator
      • skipping my funeral
      • dantheman
      • 1 yr ago
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       albedo  I don't know that they are normalizing but am just guessing. Also I'm wondering what is really being measured here? Consider, the original researcher did statistical analysis to correlate methylation to bio age. This should calibrate out (or perhaps better 'include') the fact that people take care of themselves differently. If the statistics/data is really good, then he could theoretically find your biological age regardless of how good you take care of yourself. The short point is that this approach may well be measuring absolute markers of age (e.g. 'tree rings') rather than lifespan.

      The more I think of it, the more I'm believing this is the case, and it's perhaps not a good measure of likely lifespan. Regardless I will be taking the test again in six months. 

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      • albedo
      • albedo
      • 1 yr ago
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      DanMcL 

      Interesting, thank you.

      Wrt repeated tests with Zymo remember to take into account the variability of their measurements at different points in time. Do they say something about this? Reason was emphasizing this aspect in one of his blogs:

      "...DNA methylation tests can be ordered from either Osiris Green or Epimorphy / Zymo Research - note that it takes a fair few weeks for delivery in the latter case. From talking to people at the two companis, the normal level of variability for repeat tests from the same sample is something like 1.7 years for the Zymo Research test and 4.8 years for the Osiris Green tests. The level of day to day or intraday variation between different samples from the same individual remains more of a question mark at this point in time, though I am told they are very consistent over measures separated by months. Nonetheless, as for the cardiovascular measures, it is wise to try to make everything as similar as possible when taking the test before and after a treatment: time of day, recency of eating or exercise, recent diet, and so forth..."

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    • Dan Did you get your second test results?

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      • Danmoderator
      • skipping my funeral
      • dantheman
      • 1 yr ago
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      aribadabar No, haven't finished the protocol yet. It's taking a while to get the hormones sorted out (two conventional MD's that didn't know what they were doing, now I've got somebody who does). I did do NAD patches and Metformin, but not Senolytics. Anyhow now I've got it all lined up and am going sequentially through the next several months, then will test again. 

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      • Larry
      • Larry.1
      • 1 yr ago
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      Dan Dr Horvath tested older than his chronological age with the test used in MyDNAage but when he retested using GrimAge he tested at his chronological age. We just have no idea what these clocks are measuring. 

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      • Joseph
      • Joseph
      • 11 mths ago
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      Dan how are you getting your metformin?

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      • MAC
      • MAC
      • 3 wk ago
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      Dan Got my DNAage test result back. Reported DNAage of 52, I am 55; 85th percentile. I only started my "interventions" about 4yrs ago, so there's 51 years of previous lifestyle baked in. My protocol: strict ketogenic, OMAD (one meal a day), daily aerobic/resistance exercise (run or spin 100km/week daily 30-45 minutes free weights. Quite of few supplements, only testosterone/DHEA as meds. In excellent physical/cardio shape NOW vs. previous 51 years. Turns out...exercise apparently INCREASES methylation, although it's deemed GOOD re lifespan. We all know that pretty much every longitudinal study shows enhanced lifespan with cardio/physical fitness.

      Modified aging of elite athletes revealed by analysis of epigenetic age markers

      https://pubmed.ncbi.nlm.nih.gov/29466246/

      "Accordingly, the complete 5‐CpG model revealed age acceleration of elite athletes and the result was more significant amongst power athletes. The modified methylation of TRIM59 and KLF14 in top athletes may be accounted for by the biological roles played by these genes. Their known anti‐tumour and anti‐inflammatory activities suggests that intense physical training has a complex influence on aging and potentially launches signalling networks that contribute to the observed lower risk of elite athletes to develop cardiovascular disease and cancer"

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      • Fred Cloud
      • Fred_Cloud
      • 11 days ago
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      MAC Have you considered taking rapamycin?

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      • MAC
      • MAC
      • 11 days ago
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      Fred Cloud yes have seriously considered it, worried about long term subtle mtor2 suppression. There are rapalogs in development that only target mtor1, but probably years away from approval. 

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      • Fred Cloud
      • Fred_Cloud
      • 11 days ago
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      MAC So stretch out the interval to 10 days or longer and it wont be an issue. Also, research is coming out that it can rewind the clock, you could always use it short term and rewind the clock and then stop using it. 

      https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6555449/

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      • MAC
      • MAC
      • 11 days ago
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      Fred Cloud The science is promising, but I'd like to see real longevity and all cause mortality data in HUMANS. Has anyone on this forum posted on epigenetic clock JUST on rapamycin? (vs. a cocktail of interventions, where teasing out rapa would be impossible).

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      • Fred Cloud
      • Fred_Cloud
      • 11 days ago
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      MAC Not for me, rapamycin offers so much more than adding a few years onto to your lifespan, so much so that I actually dont care if rapamycin extends life or not I would still take it. Are you under the impression that it only has the promise of life extension?

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      • MAC
      • MAC
      • 11 days ago
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      Fred Cloud I am so healthy, superb physical shape, eat strict keto, OMAD. Exercise religiously. Never had any illness, or taking any meds. My biomarkers are stellar. Why would I take it? 

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      • Fred Cloud
      • Fred_Cloud
      • 10 days ago
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      MAC Impressive, probably no need to take it yet then. Well then what is your interest in this group if you dont need to reverse your age?  Usually people in here are feeling their age.

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      • MAC
      • MAC
      • 10 days ago
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      Fred Cloud damn, was hoping you’d have some other compelling science pathway to convince me! I am interested in continuous health/lifespan improvement, looking to learn wherever I can. Ultimately my doctor and I discuss interventions and proceed accordingly. My first priority is exercise diet, and sleep,  not Pharma. I don’t believe popping a pill will rescue you if you have metabolic dysfunction or not in prime physical shape. 

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      • Fred Cloud
      • Fred_Cloud
      • 10 days ago
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      MAC Seriously? You want me to keep trying? It sounds like you are trying to make a good case of why you dont want to take it. All I can add is that early life interventions often payoff way later in life. Dr Sabatini had taken rapamycin early in his career when he was young and now decades later after not taking it for a long time he looks incredibly young for his age. We are built to have autophagy through fasting throughout life and none of us are getting it at early ages. Not sure if you do regular water only extended fasting of several days or not, you could always do that and that would be more ideal than rapamycin.

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      • MAC
      • MAC
      • 10 days ago
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      Fred Cloud Yes my default is NO, unless otherwise swayed. I've not ventured into the water only/extended fasts. With my exercise regiment, I'd loose too much weight, then have to do big re-feeding, and I don't want that type yo yo and social disengagement. The daily keto/OMAD is generating a very intense ghrelin signal (highly neurobioenergetic) and super low blood sugar/insulin (borderline hypoglycemic most days) is sending strong signal to the body. My doctor tried to lower by TSH and raise my free T3 early on with meds...but all in vain, it would NOT budge. The strict keto/OMAD was blunting the TSH and T3...my body was revving so slow, it could do with much less free T3. The brain "thinks" I am starving myself, yet, I've been weight stable for 2yrs+. I showed him the literature, he finally relented. Re Sabatini, n=1 is not convincing science. My mom is 81, she's never taken a med in her life...her skin looks like a 50 yr old.

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      • MAC
      • MAC
      • 10 days ago
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      Fred Cloud while on the n=1 indications, most all of my peer group have significant grey hair, yet I have just have some threads at 55 yo. No one has undertaken the interventions I have. Conicidence, association, causation? My doctor thinks it’s my lifestyle mediated. 

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      • Paul Bee
      • Paul_Bee
      • 9 days ago
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      MAC you should read Cracking the Aging Code by Josh Mitteldorf

      evolutionary biology is programmed to kill your body off. Diet and exercise won’t save you.

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      • MAC
      • MAC
      • 9 days ago
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      Paul Bee I will have a look thanks Paul, I follow Josh's blog, fascinating, especially the comments. I am not looking for "saving", simply enhanced health-span/lifespan. Just trying to be very fit and strong in old age. There is no other proven lifespan extension in humans (talking hundreds of RCT longitudinal studies) than cardiorespiratory fitness. Everything else I do...rolling the dice.

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  • Questions about Horvath's DNAm Age

        Steve Horvath's DNA methylation clock is based on the presence or absence of methylation at 353 (out of many thousand) CpG sites on a human or animal genome.  The sites selected were best correlated with age while being independent of cell type.  This clock has become the standard for determining the "biological age" of tissue, blood, and urine samples. I've had my DNAm age done by Zymo on two blood samples taken at the same time using some version of this technique.  They were both just a bit below my calendar age and one was about 2 years different from the other.

         I have recently been studying several papers by Horvath and others on DNA methylation vs. aging, and I've also watched his video interviews and presentations.  However, as a physicist interested in mechanism, I find that there are basic questions that do not seem to be addressed in any of these DNAm papers or videos that I have read or watched.  Perhaps some of you are more knowledgeable than am I about this area, so let me present my questions here: 

    (1) Of the 353 CpGs selected by Horvath for use in determining the DNAm age, how many of them have a positive correlation (increase with age) and how many of them have a negative correlation (decrease with age)?

    (2) Of the 353 CpGs selected for use in determining the DNAm age, how many of them are located in the non-coding region of DNA, how many of them are located in the coding region of DNA, and how many are located in CpG islands in protein promoter regions?

    (3) Does the methylation of a particular DNA region cause gene expression or gene silencing?  What's the mechanism?

    (4) David Sinclair discusses epigenetic acetylation and methylation almost interchangeably.  What are the respective roles of acetylation and methylation in determining the activation of a DNA region (switching on/off a gene)?  Is there also an acetylation clock?

    (5) Is there any discernible pattern to the methylated DNA locations of the very young vs. the very old?

    (6) If a subject's DNA was cleared of all methylation, what would be the result?

     

    Answers, anyone?

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  • A Few Answers to my DNAm Age Questions

        I've read further and have found tentative answers to some of my questions listed above.

    (1)   About 2/3 of the CpG sites used by Horvath have methylation that is positively correlated with age, while about 1/3 have methylation that is negatively correlated with age.  That means (see below) that twice as many genes are being silenced as we age as are being newly expressed (at least for those sites that show up in the profile Horvath uses).

    (2)  Many (most?) of the Horvath sites are in CpG islands in protein promoter regions.

    (3&4)  Methylation tends to silence gene expression by blocking the promoter region, while acetylation tends to promote gene expression by exposing the promoter region to transcription factors. 

    (6) The subject would die.  The methylation pattern is part of the selective epigenome that fixes the functions of particular cells (all with identical DNA) so that they become neurons or muscle cells or liver cells or skin cells or fat cells.   With no methylation they would lose their identity and cease to function correctly.

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