Nature medicineJul 9, 2025

Blood proteins connect brain and immune system aging with healthy lifespan and longevity

Longevity & Aging Weekly Brief ↗PubMed ↗DOI ↗OA ↗

Updated Mar 19, 2026

Abstract

Plasma proteomics data from 44,498 individuals identified aged organs as significant predictors of mortality risk.

Organ age estimates were influenced by lifestyle factors and medications.
An aged brain is associated with a (HR) of 3.1 for Alzheimer's disease, comparable to the genetic risk from one copy of APOE4.
A youthful brain (HR = 0.26) protects against Alzheimer's disease, akin to carrying two copies of APOE2, regardless of APOE genotype.
The risk of mortality increased with the number of aged organs: 2-4 aged organs (HR = 2.3), 5-7 aged organs (HR = 4.5), and 8+ aged organs (HR = 8.3).
Youthful brain and immune systems are linked to lower mortality risk (HR = 0.60 for a youthful brain, HR = 0.58 for a youthful immune system, and HR = 0.44 for both).

Simplified

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 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 years' 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 ( (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.

Key numbers

3.1×

Increased Alzheimer's Disease Risk

Risk associated with having an aged brain.

8.3×

Mortality Risk Increase by Organ Aging

Risk associated with having 8+ aged organs.

0.26

Youthful Brain Protection

for risk of Alzheimer's disease with a youthful brain.

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Funding

Competing interests

Competing interests: T.W-C., H.S.-H.O. and J.R. are co-founders and scientific advisors of Teal Omics, Inc. and have received equity stakes. T.W-C. is co-founder of Vero Biosciences. The remaining authors declare no competing interests.

PubMed

Blood proteins connect brain and immune system aging with healthy lifespan and longevity

Abstract

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Competing interests

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Abstract

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