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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Chronologically, I just turned 70. Being fit and never having had health problems, I never paid much attention to my health. My diet was reasonably good and I was fairly active - but never went to a gym or used weights. So I just sat down and said, OK, aging comes with new challenges and I better pay attention. I started looking for information and after a little wandering around, I landed here on this forum. It’s been a tremendous resource, full of like-minded people - curious, intelligent and willing to think outside the box (the medical establishment) while still relying on science.
I think our goals are generally the same - how to stay as physically healthy and mentally sharp as possible (for me longevity is a secondary benefit). Just by shifting focus, as I said, before I was lazy - I’m stronger and more muscular now than ever. I see others here (like Agetron) that may be the same.
My point is that in pursuing these goals (mental and physical fitness as we age) we have more and more (too many) promising options but need a better yardstick to measure results with. I expect many better yardsticks will be showing up but what will they cost?
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How old are your really? I doubt the aging clocks determine biological age.
As Richard Miller states in 29:17, aging biomarkers are like the odometer. These aging clocks or aging rate indicators are the speedometer. The speedometer does not tell you how many miles you traveled (how old you are). It only tells you how fast you are travelling (to 100, or frailty, or death). So that 46 year old billionaire fella
He is using aging clocks to quantify his health and try and reduce his biological age. He claims that he has reduced his biological age by 5.1 years and that this is a world record.
He is traveling to 50 years (or 100), at the speed of a 40.5 year old. But he is still at milepost 46. His efforts did not bring him back to milepost 41.
There is one organ in the human body that has stopped at a youthful milepost.
UC San Diego Health Health Library | San Diego Hospital, Healthcare"No%20matter%20if%20you%20are,be%20protective%2C%20the%20researchers%20said.
“No matter if you are 20 or 84, your liver stays on average just under three years old,” Bergmann said.
Not all liver cells are that young, however. A fraction of cells can live up to 10 years before renewing themselves. These cells carry more DNA than typical liver cells and could be protective, the researchers said.
Full text below:
https://www.cell.com/cell-systems/fulltext/S2405-4712(22)00171-5
That, to me, should be the Holy Grail - to study how the body keeps the liver eternally young, and apply it to other parts of the body - the heart, kidneys, lungs, etc… Imagine if your skin could be as smooth and supple as a three year old’s skin. We look around for the answers in other mammals, but the human body seems to already have the Fountain of Youth. It just has to be decoded.
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As I understand what Richard Miller was saying, the difference between Aging Rate Indicators (ARIs) and Aging Biomarkers would be like looking at the plaque buildup in arteries (biomarker) compared to the amount of cholesterol currently in the blood that is about to be deposited (Indicator).
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People can probably guess what is different about the liver (in terms of membrane transport proteins) if I am asking the question.
Great article!
"Over a four-hour period, they performed more than two dozen assessments. At first it felt a bit like an annual physical. They checked my blood pressure, weight, glucose and cholesterol.
But then, the tests got a lot more interesting. Inside a small exam room, a medical assistant opened the hinge of a BodPod, a capsule that looks like a submersible. The machine assessed my body composition, determining the ratio of fatty mass to lean mass, which includes muscle. Strength is a key marker of healthy aging, helping us fend off frailty and falls.
Next, I was asked to sniff and identify a range of distinct smells — from leather to chocolate — to test olfactory function. The loss of smell can be an early sign of disease and cognitive decline. They scanned my retina and took digital images of the inside of my eyes, which can also help detect disease. And I took a memory and cognitive function test, called MOCA. Thankfully, all was healthy.Then I went through a slew of cardiovascular health tests. They measured my endothelial function, which keeps blood flowing smoothly through the body. They looked at my heart rate variability and pulse-wave velocity, which is an indicator of stiffness of the arteries. I had electrodes placed onto my chest for an electrocardiogram."
Now, there’s the kind of testing we need! Do you think Bryan Johnson gets anything like that? Surprised that they didn’t check eyesight and hearing (but did olfactory). And apparently they endorse GrimAge.
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I agree. We need to pull together a “BioHacker Optimal Longevity Biomarkers”, and related “Biohackers Longevity Assessments and Tests” together from all these different groups. Put them in a single page so people can easily find them, then regularly (every 6 months or year) and track them as we try different therapeutic approaches / supplements / drugs, etc.
I’m sure Bryan Johnson gets all this and much more…
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Yes. Please let’s follow through on this. A great idea.
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Lots of very promising work being done on epigenetic clocks. First a current look that talks to Horvath and Levine:
This says they could get cheaper.
https://www.nature.com/articles/s43587-023-00555-2
And here is one of the newer ones:
https://www.biorxiv.org/content/10.1101/2023.03.01.530561v1.full
And they work on mice.
Collectively, the results described here with primary cells from a large number of donors and multiple cell types, as well as in vivo mouse experiments previously reported38,39, indicate that nutrient sensing, mitochondrial function, stem cell exhaustion and altered cell–cell communication affect epigenetic aging as measured by Skin&blood clock, but cellular senescence, telomere attrition and genomic instability do not (Fig. 4h). The connection of epigenetic aging to four of the hallmarks of aging implies that these hallmarks are also mutually connected at a deeper level. If so, epigenetic clocks will be instrumental in identifying the underlying unifying mechanisms. The absence of a connection between the other aging hallmarks and epigenetic aging suggests that aging is a consequence of multiparallel mechanisms, crudely divided into deterministic pathways: those associated with epigenetic aging and stochastic ones, which are independent of epigenetic aging and may result instead from wear and tear. This brings together two long-argued causes of aging. It is clear that epigenetic clocks have and will continue to bring even greater clarity to the overall process of aging. The described work is limited by the absence of animal experiments, which are now made possible with the recent availability of mouse and universal mammalian epigenetic clocks.
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