Blood test can reveal if you are at risk from organs aging prematurely

Scientists can now accurately predict which vital organs are likely to fail first with a simple blood test meaning heart failure and Alzheimer’s disease could be treated early….‘

‘…… Therefore, by measuring the levels of these proteins in the blood, the researchers were able to tell how aged each of the 11 organ systems that they tested for was—including heart, fat, lung, immune system, kidney, liver, muscle, pancreas, brain, vasculature and intestines. The algorithm could also guess how old the person was based on the 5,000 proteins in the blood, finding that the organs within a person’s body often aged at very different rates.

The researchers then developed an organ “age gap” representing the difference between an organ’s true biological age and its estimated age based on the algorithm’s predictions based on the proteins in the blood.

They discovered that in 10 of the 11 organs (all but the intestines), a larger age gap was associated with an increased risk of death over the next 15 years, both relating to the organ in question and all other reasons. Organs defined as having “accelerated aging” had a 15 to 50 percent higher mortality risk over the next 15 years.

In particular, those with faster-aging hearts were 2.5 times more likely to experience heart failure, and those with faster-aging brains were 1.8 times more likely to experience cognitive decline’

Organ aging signatures in the plasma proteome track health and disease

Animal studies show aging varies between individuals as well as between organs within an individual1,2,3,4, but whether this is true in humans and its effect on age-related diseases is unknown. We utilized levels of human blood plasma proteins originating from specific organs to measure organ-specific aging differences in living individuals. Using machine learning models, we analysed aging in 11 major organs and estimated organ age reproducibly in five independent cohorts encompassing 5,676 adults across the human lifespan. We discovered nearly 20% of the population show strongly accelerated age in one organ and 1.7% are multi-organ agers. Accelerated organ aging confers 20–50% higher mortality risk, and organ-specific diseases relate to faster aging of those organs. We find individuals with accelerated heart aging have a 250% increased heart failure risk and accelerated brain and vascular aging predict Alzheimer’s disease (AD) progression independently from and as strongly as plasma pTau-181 (ref. 5), the current best blood-based biomarker for AD. Our models link vascular calcification, extracellular matrix alterations and synaptic protein shedding to early cognitive decline. We introduce a simple and interpretable method to study organ aging using plasma proteomics data, predicting diseases and aging effects.

https://www.nature.com/articles/s41591-023-02296-6

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Anyone creating a test available to the public?

Its interesting… this seems to be an area of increasing research.

At the Longevity Summit this week I spoke with Raghav Sehgal, a researcher out of Yale (a guy from Morgan Levine’s group) who had a poster on an organ aging clock that looked very interesting. Here is a photo of it below.

These will likely be available soon from companies (and hopefully published with more information):

Steve Horvath mentioned at the conference he sees the Biomarker world doing in two direction, the “Groupers” and the “Splitters”. The groupers are trying to gather up signals from all sorts of variables in the body to come up with a single measure of “biological age” and the “splitters” are trying to narrowly divide up the body into specific areas of focus with specific biomarkers for each region/organ, etc.

This one is from one of the “Splitters”:

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The source code is here on GitHub but you need the bio banks data to use it.

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Looks like they are launching a product/service:

More info here

https://www.rapamycin.news/t/teal-proteomics-2024-launch/10965

One can pre-sign up here

https://www.rapamycin.news/t/teal-proteomics-2024-launch/10965/5

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Can Organ Aging Clock Foretell Cognitive Decline?

For brain, the authors linked a set of 49 proteins to rapid aging and dementia risk. The proteins predicted cognitive decline better than did plasma p-tau181. Many of them are expressed in synapses, myelin, and the vasculature, suggesting that defects in these systems could foreshadow decline. The data could point toward new biomarkers and therapeutic targets, Wyss-Coray told Alzforum.

Brain aging associated with cerebrovascular disease. Curiously, Alzheimer’s disease was most closely linked to overall organismal aging, rather than to a specific organ, suggesting that many systems contribute to it. Partly, this may be because the organismal aging protein set includes many vascular, metabolic, and immune proteins that are found in brain, but are not specific to it.

To home in on the proteins responsible for cognitive slippage, the authors looked for brain-specific proteins that correlated with worsening CDR scores. They identified 49, many of them active in synapses, myelin, and extracellular matrix. The set included the synaptic proteins complexin and neurexin, oligodendrocyte proteins carnosine dipeptidase 1 and LancLike Glutathione S-transferase 1, and ECM proteins tenascin R and heparan sulfate-glucosamine 3-sulfotransferase 4. This “CognitionBrain” protein set predicted decline, with people one standard deviation higher on the scale having a third higher risk of sliding by two points on the CDR over the next five years.

The CognitionBrain protein set predicted decline better than did plasma p-tau181, baseline CDR, or an AD polygenic risk score (Apr 2022 news). Combining CognitionBrain and plasma p-tau181 boosted overall predictive accuracy, suggesting the plasma proteins capture distinct information that is separate from amyloid and tau pathology.

https://www.alzforum.org/news/research-news/can-organ-aging-clock-foretell-cognitive-decline

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Just a general note on this approach at determining biological age for humans / organs… at the recent Longevity Summit the issue of biological clocks came up frequently in presentations and discussions. I think it was Steve Horvath that made the comment that the " …omics" (as in proteomics, etc.) type of clock were still very expensive as far as gathering the data… and that the perspective is that to become widely adopted and used the clock needs to be inexpensive to perform, and by inexpensive he cited a cost of “ideally under $5, but definitely not higher than $10”.

I don’t know the cost to get this new clock calculated (i.e. the cost to get the proteomics data used in the test) but given that this is at the stage of a research project, its likely still at the cost level of thousands, if not tens of thousands of dollars right now. And this is without the profit requirements of any company making this type of test available to the public or clinics.

For what it is worth I think insurance would cover these if predictive value is good at around an order magnitude higher than the 5-10 dollars. Many often used single Quest and LabCorp tests are 40 dollars or more, more specialized ones are even higher and tests like ColoGuard costing a couple of $100 seem to be covered by most insurance.

Then of course CT scans, MRIs etc are much more expense and often covered to in many contexts at least.

So think question to a large extent is about how valuable the data / info / predictive value would be

You might be right. But my guess would be that given that they launched the company in a way that seems to be targeting a consumer market, they will have some form of offering that many (though far from most) could consider buying as a normal credit card transaction, so <$1000, perhaps <$500 to not be massively higher than the Iollos, TrueDiagnostics and InsideTrackers of the world.

Its a start in the right direction… and perhaps if it proves to be accurate and becomes well-validated, then I can see myself paying a few hundred dollars for such a test every year or perhaps more frequently.

I think that Steve Horvath was talking about a type of inexpensive test that could be rolled out widely to be used in large clinical trials, in humans and animals, and widely used by the research community… so he’s talking about a different sort of application than a premium consumer type of product (which most of the bioclocks are …

Steve, also said this (below) last week. I’m not sure if he would generalize to all bioclocks, but I suspect so.

I’d still disagree with him on that I thing - as I each of these things that I mentioned are also routinely listed in pre-clinical studies and in clinical trials

Many often used single Quest and LabCorp tests are 40 dollars or more, more specialized ones are even higher and tests like ColoGuard costing a couple of $100 seem to be covered by most insurance.

Then of course CT scans, MRIs etc are much more expense and often covered to in many contexts at least.

Could it be that he actually has a path to making epigenetic testing at only 10ish dollars per test? (Would not surprise me, given that sequencing and automation and big data are on at least More’s Law type of Trajectories)

And now laying out rationale now for how that will be crucial?

The new research, published on Wednesday in Nature, identified about one in five healthy adults older than 50 years old as an “extreme ager”—a person with at least one organ aging at a highly accelerated rate, compared with a cohort of their peers. One in 60 adults had two or more organs that were aging rapidly. The study team measured proteins related to organs, including the brain, heart, immune tissue and kidneys. The researchers hope their findings will lead to a future blood test that can pinpoint rapidly aging organs, letting doctors target them for treatment before disease symptoms begin.

The team sampled the blood of more than 5,500 people, all with no active disease or clinically abnormal biomarkers, to look for proteins that originated from specific organs. The scientists were able to determine where those proteins came from by measuring their gene activity: when genes for a protein were expressed four times more in one organ, that designated its origin. Next the team measured the concentrations of thousands of proteins in a drop of blood and found that almost 900 of them—about 18 percent of the proteins measured—tended to be specific to a single organ. When those proteins varied from the expected concentration for a particular chronological age, that indicated accelerated aging in the corresponding organ.

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More on this @RapAdmin - one method two orders of magnitude cheaper:

benchmark favorably against conventional methods despite being up to 100-fold less expensive.

https://www.nature.com/articles/s43587-023-00555-2

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