Wow, certainly useful but a lot to digest. There’s so much information, the challenge is trying to structure it in a way that is actionable and then connect it to what’s measurable (biomarkers) so you can gauge what works most efficiently.
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Yes, I suspect little of the information in that paper is “actionable”, its just interesting to see where the current trends are in research, and how they target the hallmarks of aging. It does perhaps provide a bit of a guide in terms of where interesting things are happening and where to look more deeply.
For example, I was not aware of the rapid increase in parabiosis papers over the past 4 years… the area with the most rapid increase in research. It seems to be a good signal to at least look at that area (i.e. parabiosis / plasmapheresis).
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Unfortunately, reminds me of vampires.
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What we want doesn’t exist. And it’s not even just hard to do, or someone would be selling it to us. But I think it’s not far off.
The bigger idea is the digital twin. I heard of the digital twin concept from Dr Price of Thorne. He says they have built a model of Alzheimer’s development that takes individual dna, lifestyle, blood markers, etc. to project whether and when (based on probabilities) a person will develop Alzheimer’s. And then they can input interventions to see which interventions wil work best. He says they will be building these digital twins piece by piece until they have the whole thing. But not yet.
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You make a good point here… he’s basically saying that you can’t compare results from different clocks because they all measure different things. Which is fine - I agree with that.
Then he goes on to say that even within a single clock the results aren’t “actionable” - which, as you suggest, basically means he thinks there isn’t much you can do that you don’t already know you should do (e.g. eat vegetables, and exercise, etc.). So he’s saying the clocks don’t provide any new value in that area.
Yes - I’m with you on this Joseph, I tend to disagree with him a bit on that later point. While its certainly unproven that a given clock test results change over time (e.g. over a day, over a week, or month) is actually a meaningful change, or just noise,(because there haven’t been any good longitudinal studies on biocloeks in people, and various interventions).
But yes, for longevity and healthspan maximalists , we believe that there is a reasonable probability that some of the things we are doing are moving the needle in the right direction (no matter how hard it is to get a read on that needle movement). Whether its rapamycin, acarbose, exercise, … we believe that the evidence is that these move things in the right direction.
I think Steven Horvath is like most scientists, its not “proven” until there are good human studies demonstrating benefit. I think we likely take a slightly more “risk/reward” approach to longevity therapeutics, so we have a different view than Steven.
But I do agree with Horvath in that because there have been no good human longitudinal studies with these bio / aging clocks, they aren’t of much proven value (e.g. the data coming out Longevity Olympics isn’t really of scientific value, even it its interesting, entertaining, and possibly indicative of some sort of health trend). So, I feel the Levine Phenotypic clock is just find for my purposes right now.
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Parabiosis (taking blood from one mammal … e.g. a younger one, and cycling to another … e.g. older one, yes - I can see the connotation.
But I think the trend is moving toward finding the beneficial factors in young blood, and removing the harmful factors in old blood, and so that perception will likely be moot soon.
I did a 3 month period of plasmapheresis as part of this clinical trial, and it was not a big deal - go in to the clinic, a cannula in one arm, another in another arm, tubes taking blood out of one arm, going into a plasmapheresis machine and then back into the other arm. Lie back and listen to a podcast for 3 hours, and then you’re back in your car and off to the next activity. Not a big deal at all. Actually a pretty enjoyable experience; when else do I get to lay down for 3 hours with my favorite podcasts in a quiet environment. It was almost “spa-like”.
I think this type of thing may be the future: Plasmapheresis Startup Looking for Clinical Trial Participants SF Bay Area
But, the cost needs to come down. The series of 6 plasmapheresis treatments I got would have been $36,000 in current clinics. Thus… Lowering the Cost / Improving Access for Therapeutic Plasma Exchange (Plasmapheresis)
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Digital twin to test interventions on would be great. But “individual dna, lifestyle, blood markers, etc.” is a lot of data and yes, it would probably be expensive.
I think most of us take a shotgun approach which obviously wastes ammunition but at least we hit some or most of the targets (and don’t risk missing the most valuable ones). Once I settle on the best testing routine and optimize as much as possible, I’ll just drop things one by one until I see a negative effect on the biomarkers. I’m certainly taking too many supplements.
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Could be, and I think the medical establishment would like something that involves going into a clinic for blood filtering or replacing blood factors. But I would prefer just being able to tune up our own biological processes to repair/correct those problems.
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For me, and I believe Agetron, this only occurred after taking high doses for an extended period.
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I like your thinking here… what we need to develop is a testing protocol for all the key variables (blood, functional, etc.) that we think may be impacted by the therapeutics / drugs / supplements people are taking. And, then track and report on how these change over time, given different inputs.
This is a little bit like what Sergey and Michael have started - but perhaps additional things could be added… Biomarker Optimization - Crowdsourcing Biomarker Knowledge by Michael Lustgarten and Sergey Vlasov
Or, just start your own Google spreadsheet to track your variables and share here in the forums occasionally so we can see how others are responding to a given treatment regimen.
Ultimately a professional version of this type of effort needs to be done by a company or academic group so that it gets rigorously tested.
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Yes, I think you talked about an App but as you said, a big project. But I think in terms of gauging results - that the Levine spreadsheet and Aging.ai may be very effective for using such a minimal dataset. But you would think that if you expanded from 10 inputs to 20-30 or more that it would be much more comprehensive. And lots of measures that are talked about here: ApoB, Cystatin C, A1c, testosterone, blood pressure, RHR, HRV, etc, we know are important.
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I’m looking again, but a thought I saw a number of people here who were still waiting for their blood markers to improve.
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I agree with you entirely.
First thing I found.https://www.rapamycin.news/t/my-insidetracker-innerage-test-results-before-and-after-rapamycin/2560/4
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I’m only suggesting that if we eliminate the epigenetic clock tests as not yet reliable enough and are mainly relying on the Levine blood test markers and Aging.ai, that they may not give us a very good picture of what rapamycin is doing. It seems that without even getting too complicated that we could incorporate a lot more measures from blood tests, home tests like blood pressure, functional and strength tests, heart rate, sleep quality, etc. that would be simple and inexpensive. And hopefully give us something more complete and quantifiable to show the improvements from taking rapamycin.
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What the tests that tell your “true age” really mean
The market is flooded with tests for “biological age,” but it’s important to understand their limitations
https://www.salon.com/2024/01/28/what-the-tests-that-tell-your-true-age-really-mean/
…
A recent New York Times profile of 46 year-old entrepreneur Bryan Johnson noted his elaborate diet and fitness routine, as well as his fixation on meticulously testing and documenting different markers of his age, from his hearing to his wrinkles to his heart health. And it noted that “His ‘biological age,’ he claimed until recently, is 42.5. … In other words, he has spent about three years shaving off — maybe — a little more than three years.” Three years and, by his own count, “millions of dollars.”
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The key as I see it is identifying functional tests that indicate the health of individual body systems. These include blood biomarkers, but also things like the sit to stand tests.
From that you can identify if any particular organ system has any specific problem and work on that.
I like Morgan Levine’s phenoage formula and other similar formulae, but they all have their difficulties and tend not to handle U shaped mortality curves that well.
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NPR
Scientists can tell how fast you’re aging. Now, the trick is to slow it down
I used to flinch at the topic of aging. Is there anything we can do about the inevitable?
But recently I’ve been digging into a new wave of longevity research that is making it an exciting time to be an aging human – which is all of us.
It turns out, we all age at varying rates. Super-agers may have great genes, but research shows our habits and routines – everything from what we eat and how we move our bodies to who we spend our time with – matter a lot, when it comes to aging well.
Now, the next frontier is to target the basic biology of aging and come up with new interventions to slow it down.
Many scientists are optimistic that we’re on the cusp of breakthroughs. Not only to help us live longer, but — more importantly — to extend the number of years we live with good health.
This is the goal of researchers at the Human Longevity Lab at Northwestern University Feinberg School of Medicine. They’re recruiting study participants so that they can test what kinds of interventions may slow the rate of aging. To that end, I decided to roll up my sleeve for science.
…
Democratizing aging
People who live in the upscale Chicago neighborhood where the Human Longevity Lab is located, can expect to live a much longer, healthier life compared to people who live just a few miles away. Dr. Vaughan wants to help close this gap.
“I’m worried about the poor soul in south Chicago who has a life expectancy of 55, compared to 92 in the neighborhood where we’re standing right now,” he says. A stunning difference of more than 30 years. (You can check out life expectancy in your zip code here.)
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My Levine age score hasn’t improved while on Rapa (May 2023) but I am much “healthier” feeling. For me anyway that shows the limitations of a simple model like Levine (even though I like it). My improvements in quality of health have come in pain elimination benefits. My hsCRP was already very low so what changed? I don’t know. I also had a rise then net fall in HbA1c, and a fall in my apoB…all would logically be good for longevity but no improvement in score.
Functional markers (strength, balance, etc) are obviously important but how to sort out the improvements from better health status and improvements from training that is covering up a poor diet, etc.
Maybe there is no benefit to an overall age score. Perhaps an organ / system score is best since it only takes one failure to get you.
I look forward to someone figuring it out.
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The theory about an overall age score is that it works out for any one intervention whether that intervention is helping or hindering. One problem, however, is that it is quite sensitive to noise in the biomarkers.
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