@Joseph_Lavelle please mote - I’m not saying what you should do or trying to convince you of anything
Just saying that any data that is collected today should be backward compatible with any future clocks and analyses that are even better and enable time series data that one can look back at. (And that time series data is very valuable on N=1 as we don’t have other controls than how we change the protocols and routines over time and how outcomes and data change over time).
Do you agree with that specific point or do you not think that specific point (that was all my post above was about) is correct?
Whether you weigh that impacting your overall decision or not is of course 100% your choice and I’m not saying it should change your overall conclusion - just that it was a dimension that did not seem to have been weighted in any of your prior posts.
Two tests, six months apart. Went from 67 to 74. OK then.
Guess I shouldn’t have taken up shooting heroiin during the interim.
Musculoskeletal and brain age increased by nine years in six months. But basically everything looks correlated. Going to hell in a handbasket on a systemic, indeed symphonic, basis.
My question is would you have seen the same thing if you took the test two days in a row, one test in the morning when fasted, one test after a big meal? The trouble is at these prices you cannot really do much test by test validation, and I’ve seen no data to suggest that the company has either.
@Neo I do think it’s a good idea for these companies to offer such a service when people like Matt Kaeberlein (and Steve Horvath?) are saying the tests are not ready for individuals to use in managing their health. I am not saying I think no one should use these tests; I’m just explaining why I don’t use them.
The key for me is to do the things that matter for my health and longevity (and my enjoyment of life). Analyzing accurate data to help me prioritize my investments of time and money is important but only if data is accurate enough and actionable. If it’s only directionally accurate (or worse), then it isn’t helping me assess small changes in my interventions (and it might confuse me). I already know the big levers. I’ll bet you do as well.
I’m working on (wil test):
eliminating visceral fat (Dexa)
lowering HbA1c (CGM, blood)
increasing mitochondrial mass (vo2max)
increasing lactate and hypoxic signaling (HIIT time)
increasing (gradually) my physical capabilities (strength, endurance, dexterity, balance, range of motion, reaction speed) - functional metrics
getting more sunshine (emphasis on red end of spectrum) - daily exposure
reducing plastic (and other pollutant) exposure (?)
lowering protein intake without losing recovery (intake vs recovery vs muscle mass)
Here is an interesting article from Feb 2024 with quotes from the leading lights.
Ultimately what I think it comes down to is: “what is the marginal benefit, vs the marginal cost”, and is it the best investment of your money (assuming its “limited” in some sense), compared to some other investment for longevity. I would prefer, for example, to put the $450 (or whatever the current price is) into doing a personal dose escalation study of rapamycin for myself - doing a complete blood test series, and blood sirolimus testing, on a regular schedule to better understand my blood/sirolimus curve, and the impact of different doses on my blood measures.
I suspect that this type of test would have much more potential benefit for my long term health and longevity than a periodic TruDiagnoistics DunedinPace test. But your thoughts may differ…
Absolutely! We all have to prioritize our time and resources. I haven’t settled on the TruDiagnostics test yet. The SimonOne body scan recently recommended by @DrFraser also looks good. What puzzles me is all the skepticism about the validity of a 3rd generation epigenetic age test. This is very well studied science at this point (3rd generation) and it’s established as valid, just not fully evolved yet. I just reviewed and I have dozens of links to studies and papers to back this up. I’ll select some good ones to post. Depending on coming launches of other omics age tests (particularly proteomics), I think we’re on the verge of a BioAge clock test that’s repeatable, reliable and accurate enough to be used as a measuring stick for longevity interventions. And the price will come down as it gains widespread use. Epigenetics are the leading candidate at this point.
Epigenetic clocks are based on pattern recognition. By analyzing large databases they see patterns in the DNA methylation sites (CPGs) that correspond very well with health states, conditions and ages. But there are hundreds of thousands of sites, so they are still researching which are the most useful sites. And they are still determining between correlation and causation. But it’s based on big statistical averages so of course there will be exceptions and outliers, but it will work for most people to tell them how they compare with the general public average for their age. And it’s likely that they will be more accurate when focused in on smaller groups, like young people or old people or possibly men and women. As @Steve_Combi has pointed out, your pace of aging normally changes as you get older and as we’ve seen that may not be linear change but may accelerate in stages.
Here is a very good but basic explanation and overview of epigenetic clocks. Everybody should at least know this much before criticizing their validity.
Read this article if nothing else, it’s short and simple.
What Is The Best Biological Age Clock?
The best epigenetic clock would be one that is trained on many powerful biomarkers of health, disease and mortality risk.
These can be real, physiological biomarkers, like the size of your brain (during aging, the brain shrinks), blood pressure, weight, dental health, facial health (if you look older, changes are your body is also older), balance, grip strength, gait speed, working memory, reasoning, and so on. It should also incorporate other biomarkers, like blood biomarkers (HDL cholesterol, inflammatory proteins, glucose levels, and so on).
One of the few clocks that actually measures various of such biomarkers, is the DunedinPACE clock. This clock has been the result of scientists tracking the health of around a thousand people for decades, regularly measuring their grip strength, dental health, brain size, memory, facial aging, and so on. All these measurements paint a more accurate picture of one’s health and biological age.
How about if you submitted the SAME sample twice? Would you get the same result?
WhenI paid for the SA report (only $15) from my first sample they also regenerated omicage. Here’s the first and regenerated ages, side by side.
I’m 71.37 calendar in both (of course, it’s the same sample) But omicage 68 ->76 eight years difference.
Their ‘disclaimer’ is seems to have slightly changed wording between the first and second. A different reference population? Maybe if you make a change like that, you should point it out? But even if that’s what happened, wtf, eight years change by changing the reference population?
Anyone who paid the $15 symphony age upgrade presumably also got a recalculated omicage. You should check to see how your omicage changed between runs.
Here’s another very good, slightly more detailed article on Epigenetic Clocks that covers the basic science and evolution.
Epigenetic Clocks – What are they?
Senescent cells that are induced via irradiation-related DNA damage and oncogene activation also don’t show increased age when measured by epigenetic clocks [35,36]. Furthermore, not all longevity drugs have been found to impact methylation age. Rapamycin reduces methylation age, for example, while NAD, NR, and Metformin do not.
Importantly, there are many other epigenetic clocks beyond the four discussed here, such as the DunedinPoAm and the DunedinPACE clocks and those developed for other species/organisms [37-40]. As interest in these clocks accelerates, they will undoubtedly continue to be improved upon. Future studies will aim to more concretely define biological aging and to further distinguish it from chronological aging. The next generation of epigenetic clocks will likely continue to become more precise, accurate, validated, and application-specific – as well as more complicated.
Beyond development, future research will also look more towards application. These clocks can be utilized to test basic theories in the biology of aging, diagnose biological age, and assess risk of age-related disease. The near future will likely see clinical trials which report changes to methylation age as exploratory outcomes [41]. Beyond longevity, these clocks also have applications in the fields of forensics, archeology, and zoology.
While much is uncertain, it seems only a matter of time until this once-niche area grows into a fully-fledged field of its own.
Here’s a recent (5 days ago) Matt Kaeberlein talk which includes a short bit about bioage clocks …start around 49:00 to 55:00. He lays out his primary objections for the current state of development.
Great podcast - I watched it all. Thanks for posting it! It’s the first Kara Fitzgerald one I’ve watched, she was good. I don’t think Matt was particularly negative on epigenetic clocks but he did say there are still questions. Kara was more positive. And I agree it’s still early, I haven’t completely decided to do it but I’m leaning positive. Price is an obstacle - however 50% off looks better. Matt certainly is a little conservative in general, notice his section about not declaring anything until we have absolute proof - maybe an anti-Sinclair stance. And even though he was a co-author on the Taurine paper, he still had his doubts.
In the end what we are trying to get is functional improvements. Hence we need to measure function and see if it improves.
I think DNA methylation is like the grass that grows on roads that are not driven down. It grows on genes that stop being used as much. Hence it can be a useful indicator.
Excellent list! And I’m with you on all of those. I still need to get a baseline VO2 max test. Hopefully we’ll soon get Continuous Lactate Monitors from Abbott which should help to monitor mitochondrial health. I would add “forever chemicals” to reducing microplastics. I guess you get your biohacker merit badge back. And I probably need to increase protein to build more muscle (I think I’m CR).
I’m with both of you on functional improvements…and, as a biohacker, testing to quantify it.
*This is a big part of what makes the Rejuvenation Olympics a good idea. A competition is somehow more motivating…“I coulda been a contender”…and even if I’m down, I can always make a shocking comeback. I’ll show them.
***Anyway, the NPR article @Joseph_Lavelle posted along with it’s companion piece that @RapAdmin had posted in another thread make a great pair and cover most of the issues here. The testing regime laid out is pretty thorough - and includes both epigenetic and functional tests. And as pointed out in the articles:
For now, says Horvath, the tests are most useful for scientists studying aging. The goal of Horvath’s nonprofit Clock Foundation is to make the GrimAge test accessible to the research community, but it’s also possible for consumers to order the test, which has been validated with published research.
After all, biohackers, are just amateur scientists studying aging with an n=1.
That’s basically addressed here (in the Kris Verburgh article).
The DunedinPACE is a rate of aging clock: it tells how fast your biological clock is currently ticking. That’s good.
However, you would also want to know the time on the clock (how much time has already passed). For this, you need a biological age clock. A decent biological age clock is the GrimAge clock (a second generation epigenetic clock).
So ideally, one does two epigenetic tests: one test to measure your rate of aging (how fast the clock is ticking now), and another to measure your biological age (the time on the clock).
From the study above that @Steve_Combi posted.
" DunedinPACE distills the 20-year pace of aging into a single-timepoint DNA methylation blood test"
" DunedinPACE shows exceptional test-retest reliability"
Gamification is a powerful motivator for many. Including me my wife has a killer instinct and is anxiously waiting her latest results with the hope she moves up the ladder LoL!
Who doesn’t like to “win” especially when it improves your life.
One finding of interest was that several methylomic clusters exhibited more variability with age. These findings corroborate a report by Slieker et al., which reported that aging is synonymous with an increase in methylomic variation [34]. According to our data, variance for distinct clusters appears to ramp up around 70 years of age. Related work from the laboratory of Dr. Tony Wyss-Coray has shown that the human plasma proteome undulates with age, with noticeable peaks of differential expression occurring at ages 34, 60, and 78 [35]. A previous meta-analysis in human transcriptomic data analogously identified a plethora of genes that were both variably and differentially expressed after age 70 [36]. While multi-omics data from the same individuals is ultimately needed to better understand how the molecular landscape becomes aberrant with age, current evidence suggests that multiple molecular systems are dysregulated in the final decades of life.
We next compared CheekAge to four other epigenetic clocks for which all CpGs were available in our dataset. Specifically, we analyzed RMSE, MAE, R 2, age bias, and test–retest error of PhenoAge [23] (Fig. 5a), Horvath et al. [24] (Fig. 5b), Zhang et al. [25] (Fig. 5c), and PedBE [11] (Fig. 5d) alongside CheekAge (Fig. 5e). As would be expected since none of these clocks were optimized for adult buccal tissue, CheekAge displayed the best overall performance (Fig. 5f), even after controlling for systematic age bias using the same rotation transformation applied to CheekAge
Notably, they did not compare to GrimAge or DunedinPace, the 2 best. But here’s an article on CheekAge in Frontiers.
To our knowledge, this is the first study to demonstrate that an aging biomarker optimized for buccal tissue can be applied to blood for mortality prediction. Our findings build on previous work by Lowe et al. (2013) from more than a decade ago, which found that buccal methylation data was highly informative for a variety of phenotypes and diseases. The magnitude of the HR for mortality prediction outcompetes all first-generation clocks tested and compares favorably to the next-generation blood-trained clock DNAm PhenoAge. These data suggest that adult buccal tissue, which is relatively painless and easy to collect in a variety of settings, may represent a rich source of aging biomarkers. Furthermore, it is encouraging that an Infinium MethylationEPIC clock trained in buccal tissue can capture mortality risk in Infinium HumanMethylation450 blood data. Because most methylation changes that occur with age are tissue-specific (Slieker et al., 2018), we hypothesize that the mortality association would be stronger in a longitudinal dataset containing either cheek swab or saliva methylation data. In summary, this work provides further evidence that CheekAge is a next-generation model and reveals novel CpGs linked to human mortality.
Also I think you may be a new leader on accelerated aging leaderboard.
my wife has a killer instinct and is anxiously waiting her latest results with the hope she moves up the ladder LoL!