How Old Are You Really? (Age Clocks)

#41

NPR

YOUR HEALTH

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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#42

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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#43

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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#44

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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#45

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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#46

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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#47

People can probably guess what is different about the liver (in terms of membrane transport proteins) if I am asking the question.

#48

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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#49

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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#50

Yes. Please let’s follow through on this. A great idea.

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#51

Lots of very promising work being done on epigenetic clocks. First a current look that talks to Horvath and Levine:

https://www.technologynetworks.com/genomics/articles/the-power-and-potential-of-epigenetic-aging-clocks-374135

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.

https://www.nature.com/articles/s43587-022-00220-0

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#52

Latest video from @ConquerAging about biological age.

Michael will also due blood analysis consultation which is available through his Patreon. A very informative video! (I’m glad my blood biomarkers are doing well!)

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#53

Thanks, very useful. Just surprising that the Levine BioAge calculator that everyone uses hasn’t been updated/improved. He even states in the video that creatinine should probably be replaced by cystatin C for people over 40. Certainly looking forward to the upcoming presentation of his about how diet and supplements directly affect each of the 9 blood biomarkers that the Levine BioAge calculator uses.

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#54

I’ve been wondering about a conversion of cystatin-c results to creatinine so I could use it in the Levine model. But I couldn’t find anything.

#55

You need to reverse engineer the eGFR formulae.

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#56

I’m all for this as well. First deciding on what the best tests/markers would be, without having too many (maybe 25-30) to make it unwieldy. Then to show it on some kind of timeline that would also show your supplements/interventions (and changes) so that you could crosscheck how changes in one set would correspond with changes in the other set. If we had a big collection of these from the users here, I believe that would give us actionable data.

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#57

Been doing a lot of searching on BioMarkers and Age Clocks. Here’s something good and recent June 2023:

https://onlinelibrary.wiley.com/doi/full/10.1002/mef2.50

And a good article on NPR:

Out of curiousity, I watched the video of Peter Attia and Matt Kaeberlein talking about epigenetic clocks and Peter says how can it be based on something so easily changeable like blood glucose levels or vitamin D levels? My understanding was that epigenetic clocks were based on DNA methylation marks. What do glucose levels or vitamin D have to do with it? Those are blood test measures.

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#58

First link:

Given the unprecedented phenomenon of population ageing, studies have increasing captured the heterogeneity within the ageing process. In this context, the concept of “biological age” has been introduced as an integrated measure reflecting the individualized ageing pace.

Second link:

If you take one of these tests, you’ll get back a number — an estimate of your biological age. You probably shouldn’t put too much stock in it, researchers say. No test can tell you exactly how long you’ll live, of course. What the test can do is estimate how fast or how slowly you’re aging compared to your peers.

Precisely what Dr. Richard Miller said. They are speedometers, not odometers. They do not tell you have old your body is, biologically. They tell you how fast you are aging. So a 50 year old with a 45 year old score, is aging as slowly as a 45 year old. But his body is not biologically 45 years old. He is just traveling more slowly than other 50 year olds, to frailty or death.

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#59

Yes, but…this is the interesting thing. Dr. Miller was saying that, and distinguishing by calling them “Aging Indicators” not BioMarkers. However, epigenetic clocks, as I understand them, are looking at methylation marks on the DNA that accumulate over time as opposed to the Levine Phenotype Blood Age Clock that is looking at what the state of your blood is at the moment. So Levine (and the ITP studies) would be the speed you are going at the moment but epigenetic clocks would record the distance covered (ergo damage done). What I don’t understand is how positive longevity interventions would demethylate/unmethylate the DNA to improve your score on the epigenetic clock bioage test. And I can’t believe that it’s as easy as improving your blood glucose level or Vitamin D level (as Peter Attia said). Another analogy would be that your lipid panel (LDL, triglycerides, ApoB) represent the speed you are going but the buildup of plaque in your arteries (the damage) is how far you have come. So, which is BioAge?

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#60

I think the point is that stress levels and vitamin D levels shift the methylation markers. Lots of things shift methylation markers, but are not necessarily an indication of improved health.

I think there are some biomarkers that strictly indicate health rather than a rate of change. One, for example, is Cystatin-C another is the background level of CRP (not the level from infection, but the level when not affected by infection).

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