I wish I had some insights to offer, but unfortunately I don’t. It does seem strange though that as someone who is generally fit you’d get those results. Maybe you are right about the allergies and autoimmune conditions. Please post an update if you learn anything more about this.vegarejuvinated wrote:Hi All - I recently ran a DNAge test to check on how my interventions were going. I’ve read that these tests based on Horvaths clock are pretty accurate and I was keen to get a sense (and honestly felt like it would make me feel good as I’m fitter than most people I know which a good body weight and healthy habits). Imagine my surprise when my bio age came back as 69 when my chrono age is 47! I have emailed DNAge but they don’t seem interested in communicating with me
I did the blood test not urine and I think this is maybe a reflection on my immune system (long standing challenges with allergies and autoimmune conditions)
Thanks in advance to anyone who can help me troubleshot this disturbing result.
Hello to an Aussie 4/4 from someone who is also ApoE 4/4 and at the chronological age of 69!vegarejuvinated wrote:... I’m fitter than most people I know which a good body weight and healthy habits). Imagine my surprise when my bio age came back as 69 when my chrono age is 47! ...
Thanks in advance to anyone who can help me troubleshot this disturbing result.
As an aside, a quick look at an earlier post of your about PPRA (G/G) as a metabolic risk gene seems to be different than articles showing it is seen in elite endurance athletes. So maybe you ARE incredibly fit and the methylation DNA test is measuring one, but not a telling, biomarker.A systematic review of 16 prospective studies concluded that physical activity decreased the risk of developing AD by 45%
...The findings also suggest that physical activity may prevent Aβ accumulation that occurs in the brains of ε4 carriers before clinical symptoms of AD even become apparent
floramaria wrote: Iwish I had some insights to offer, but unfortunately I don’t. It does seem strange though that as someone who is generally fit you’d get those results. Maybe you are right about the allergies and autoimmune conditions. Please post an update if you learn anything more about this.
NF52 wrote:Hello to an Aussie 4/4 from someone who is also ApoE 4/4 and at the chronological age of 69!
vegarejuvinated wrote: I’ve read that these tests based on Horvaths clock are pretty accurate and I was keen to get a sense (and honestly felt like it would make me feel good
Biomarkers of aging and epigenetic clocks [1:29:15]
What would biomarkers for aging look like?
When Peter had Eileen White on the podcast, she pointed out that we don’t even have biomarkers for something as important as autophagy
We don’t know how long a human should fast to generate a meaningful amount of autophagy (in mice it’s a day, and in humans 7 days is likely enough, but we don’t precisely know)
We can measure telomere length, but Peter does not think this is a helpful measurement for aging: “I think there’s plenty of data to suggest that while telomere length is a very important marker of cellular division, it really speaks very little about the organism’s state of aging”
Peter doesn’t think epigenetic clocks are useful either because they can easily be manipulated by short-term interventions that don’t seem biologically relevant
The epigenetic clock refers to chemical marks on DNA that regulate gene expression (whether or not a gene is turned on or off)
these marks change with age in pretty much every organism where it’s been studied
We have identified patterns of change at specific locations in the genome that correlate very strongly with chronological age
So we have tried to create clocks that look at specific chemical marks in the DNA to determine how long that that organism has been alive
You can identify individuals whose chemical marks are not in line with what we would expect given their chronological age
They seem to be aging faster or more slowly than expected
And indeed, those individuals who tend to be off the line turn out to be at lower or higher risk for specific diseases depending on whether they seem to be aging more slowly or more quickly
This adds some weight to the argument that epigenetic clocks are measuring biological age
Can we develop epigenetic clocks that will, in a predictive way, tell you how old you are biologically?
Some companies are selling these tests right now
Human tests are based on markers in the blood, but it’s not clear whether the “biological age” of the blood reflects the biological age of the entire body
They are mostly looking at peripheral blood mononuclear cells (PBMCs) and maybe saliva tests, but Matt’s not sure how the commercial companies are doing it
Peter discounts clocks that use inputs like glucose or vitamin D level, because they vary widely from day to day and are easy to manipulate
Matt thinks the data and correlations of epigenetic clocks are strong
But he’s skeptical that there are so many data points in the epigenome that you can find a pattern that will fit pretty much anything you look for
It may not be a robust predictor of biological age, but they are telling us something
Peter would like to have Steve Horvath on the podcast to talk about the details of data from epigenetic clocks
Matt says that people are now “going beyond the epigenetic clocks to try to look at every possible thing you could measure, sometimes combining that with the epigenetic clock to build these multi-element clocks”
Now you have tens of thousands of additional data points, which makes it more likely you can find a pattern
We’re not yet at the point of getting to biological explanations for what the patterns are telling us
Are the genes at the mark locations causal for biological aging in any way? We’d need to understand the mechanism to know
“We have a lot of biomarkers of aging. We just don’t have any validated biomarkers of aging. …You can identify all sorts of things that correlate with age. How do you get to the point of convincing yourself … that these things are actually telling you something about biological aging that can then be used to understand whether an intervention is working?’” —Matt Kaeberlein
The goal would be to develop a test you could take to find out if something you are doing (fasting, taking metformin or rapamycin, etc.) is working based on a set of biomarkers
We are not there yet
Prospects of a test that could calculate biological age [1:37:45]
Steve Austad was recently on the podcast and made a similar point about the ITP studies
They out a lot of time and money into it, but you can argue that the technology simply wasn’t mature enough
Now, 30 years later, we have “omics,” machine learning, etc.
Maybe it could be done today, but it might be too disjointed a project for academia
But it’s not a particularly good commercial endeavor because you’d have to invest far too much up front before it would pay off
“someone’s got to pony up a lot of money to develop the foundation of a pyramid that will ultimately become a great tool for drug discovery”
Matt thinks there isn’t much of a barrier to doing it pre-clinically now
You could do a multiomic analysis of aging in mice
Apply machine learning to identify patterns that predict the effect of interventions and individual outcomes for longevity
Would be restricted to looking at blood if wanted to do a longitudinal study because you could not kill the animals
The biotech company Calico has the resources and expertise to do this kind of study
They are interested in multiomic signatures of different aging processes
They’re a kind of hybrid between academia and industry
You could develop a test of, say, 24 factors that give you 95% confidence on remaining life
Then you could do an independent study to see if it works
It would be really impressive if you could predict how long mice would live at the individual level when they are 6 months old, and even more impressive to show that a specific intervention can predict they’re going to live 30% longer
But you can’t use this approach in humans
It takes a long time to do the validation step and know that you have actually changed somebody’s biological state so that they are at lower risk for disease and are likely to live some X percent longer
You are almost obligated to have some level of faith in the test at that point
It’s not clear what you’d have to do before you could convince regulators that you can actually go out and tell the general public that this test works (although they are not really stopping people who are already doing that)
Tincup wrote:In this Peter Attia interview with Matt Kaeberlein they talk about these biomarkers and gave their opinions, which don't seem as positive as you might expect.
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