Can a routine blood draw tell us how fast our organs are aging?
Researchers have found that proteins in the blood may estimate the biological age of major organs and predict future risks of disease and death.
The study analyzed data from 44,498 individuals aged 40 to 70 years using plasma proteomics—a technique that measures proteins circulating in blood.
The team developed aging models for 11 organs: brain, heart, kidney, liver, lung, pancreas, intestine, immune system, artery, adipose tissue, and muscle. Machine learning was used to predict biological age based on organ-specific proteins. The difference between predicted and chronological age was defined as an age gap, with positive gaps indicating older-than-expected organs.
Individuals with older-appearing organs, particularly the brain and immune system, were more likely to develop chronic diseases and die during the 17-year follow-up. A one standard deviation increase in brain age was associated with a 59% higher mortality risk. Those with aged brains had a threefold increased risk of developing Alzheimer’s disease. Conversely, people with youthful brains had a 74% lower risk, independent of age, sex, and APOE genotype.
"The brain may be a central regulator of lifespan in humans," wrote co-author Tony Wyss-Coray of the Department of Neurology and Neurological Sciences at Stanford University School of Medicine, and colleauges, “similar to findings in animal models (worms, flies and mice).”
Risk increased with the number of aged organs. Having 2 to 4 aged organs was associated with a 2.3-fold higher mortality risk, while having 5 to 7 and 8 or more aged organs was linked to 4.5-fold and 8.3-fold increased risk, respectively. Over 60% of individuals with 8 or more aged organs died within 15 years.
In contrast, individuals with youthful brains and immune systems had the lowest mortality risk. This group showed a 58% reduction in risk compared to average agers. These associations were independent of traditional biomarkers such as estimated glomerular filtration rate and PhenoAge.
Organ age gaps were influenced by lifestyle and medication. Smoking, alcohol intake, processed meat consumption, and insomnia were associated with accelerated organ aging. Vigorous exercise, oily fish intake, and use of supplements such as vitamin C, cod liver oil, and glucosamine were associated with younger organ profiles.
Several brain proteins strongly contributed to aging estimates. These included neurofilament light chain (NEFL), a marker of axonal injury; glial fibrillary acidic protein (GFAP), related to astrocyte reactivity; and brevican (BCAN), a structural extracellular matrix protein. NEFL had the highest predictive weight in the brain aging model.
Plasma-based brain age was only weakly correlated with MRI-based brain age but both predicted Alzheimer’s disease risk, suggesting they capture different biological processes. MRI-based models were more reflective of structural loss, while plasma-based estimates likely incorporated molecular changes related to inflammation, glial activity, and extracellular remodeling.
The findings suggest plasma proteomics may serve as a noninvasive tool for estimating biological organ age, identifying individuals at higher risk for chronic disease and mortality, and evaluating lifestyle or pharmaceutical interventions. Researchers emphasized the central role of brain and immune system aging in influencing overall longevity.
Full disclosures can be found in the published study.
Source: nature medicine
