Plasma proteomics and brain aging (Wyss-Coray Lab)

#1

Plasma proteomics links brain and immune system aging with healthspan and longevity

Plasma proteins derived from specific organs can estimate organ age and mortality, but their sensitivity to environmental factors and their robustness in forecasting onset of organ diseases and mortality remain unclear. To address this gap, we estimate the biological age of 11 organs using plasma proteomics data (2,916 proteins) from 44,498 individuals in the UK Biobank. Organ age estimates were sensitive to lifestyle factors and medications and were associated with future onset (within 17 yearsʼ follow-up) of a range of diseases, including heart failure, chronic obstructive pulmonary disease, type 2 diabetes and Alzheimer’s disease. Notably, having an especially aged brain posed a risk of Alzheimer’s disease (hazard ratio (HR) = 3.1) that was similar to carrying one copy of APOE4 , the strongest genetic risk factor for sporadic Alzheimer’s disease, whereas a youthful brain (HR = 0.26) provided protection that was similar to carrying two copies of APOE2 , independent of APOE genotype. Accrual of aged organs progressively increased mortality risk (2–4 aged organs, HR = 2.3; 5–7 aged organs, HR = 4.5; 8+ aged organs, HR = 8.3), whereas youthful brains and immune systems were uniquely associated with longevity (youthful brain, HR = 0.60 for mortality risk; youthful immune system, HR = 0.58; youthful both, HR = 0.44). Altogether, these findings support the use of plasma proteins for monitoring of organ health and point to the brain and immune systems as key targets for longevity interventions.

Open access paper:

https://www.nature.com/articles/s41591-025-03798-1

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#2

brain age, conventional age, PhenoAge and sex were key predictors in the combined model (Fig. 4c). Application of FIBA to understand contributions of brain and conventional aging model proteins on mortality risk highlighted BCAN, NEFL and PTPRR from the brain as well as ectodysplasin A2 receptor (EDA2R, organismal protein), chemokine C-X-C motif ligand 17 (CXCL17, organismal protein) and elastin (ELN, artery protein) from the conventional aging model as important proteins (Extended Data Fig. [6c]

https://www.nature.com/articles/s41591-025-03798-1#Fig10

#3

writeup from Stanford PR dept. I have to wonder if this is the test that is being commercialized by Teal: Teal Proteomics 2024 launch - Organ Specific Biological Clock

“We’ve developed a blood-based indicator of the age of your organs,” said Tony Wyss-Coray, PhD, professor of neurology and neurological sciences and director of the Knight Initiative for Brain Resilience at the Wu Tsai Neurosciences Institute. “With this indicator, we can assess the age of an organ today and predict the odds of your getting a disease associated with that organ 10 years later.”

They can even predict who is most likely to die from medical conditions associated with one or more of the 11 separate organ systems the researchers looked at: brain, muscle, heart, lung, arteries, liver, kidneys, pancreas, immune system, intestine and fat.

The biological age of one organ — the brain — plays an outsized role in determining how long you have left to live, Wyss-Coray said.

In other words, someone with a biologically old brain is approximately 12 times as likely to receive a new diagnosis of Alzheimer’s disease over the next decade or so as someone the same age with a biologically young brain.

In addition, Wyss-Coray said, brain age was the best single predictor of overall mortality. Having an extremely aged brain increased subjects’ risk of dying by 182% over a roughly 15-year period, while individuals with extremely youthful brains had an overall 40% reduction in their risk of dying over the same duration.

Although the analytical tool is available only for research purposes now, Wyss-Coray has plans to commercialize it. He is a co-founder and scientific officer of Teal Omics and Vero Bioscience, two companies to whom Stanford University’s Office of Technology Licensing has licensed technology developed in this and related research for commercializing, respectively, screens for new drug targets and a consumer product.

The test could be available in the next two to three years, Wyss-Coray said. “The cost will come down as we focus on fewer key organs, such as the brain, heart and immune system, to get more resolution and stronger links to specific diseases.”

Websites of companies commercializing this technology:

https://www.verobioscience.com

#4

So, another TruDiagnostic.

#5

Organ-specific clocks seem much more valuable and actionable to me… though of course the need to be validated by third parties, and more evidence provided.

#6

I think the company is called Vero?

#7

Then you’ll be wanting the TruDIagnosit SYMPHONYAge reports -

https://www.trudiagnostic.com/symphony-age