The biological age of the brain – not the number of candles on a birthday cake – may also be the strongest predictor of how long you will last.
Researchers at Stanford University analyzed blood samples from nearly 45,000 people and found that people with “young” brains live significantly longer than people with brains too early, even if they are the same age.
The study, published in Natural Medicine, shows that the same person’s organ age varies greatly. By measuring nearly 3,000 proteins in blood samples, scientists can now estimate the biological age of 11 major organs and predict the risk of disease in previous years of symptoms.
The brain as the gatekeeper for longevity
“The brain is the gatekeeper of longevity,” explains Tony Wyss-Coray, professor of medical neurology and neuroscience in Stanford. “If your brain has an old one, then the chance of death is increased. If you have a younger one, you may live longer.”
People with extremely high brain age face 3.1 times more suffering from Alzheimer’s disease, which is consistent with carrying a copy of APOE4, the strongest genetic risk factor for the disease. In contrast, those with younger brains have 74% protection against Alzheimer’s, similar to having two copies of the protective APOE2 gene.
The mortality difference is shocking. Over a 15-year period, older brains showed an increased risk of death in 182%, while younger brains showed a 40% lower risk of death.
Organ-specific disease prediction
A team led by Hamilton OH identified organ-specific proteins circulating in the blood that reveals the biological conditions of each organ. About 15% of the measured proteins come from a single organ, creating different molecular characteristics for the brain, heart, liver, kidney and other systems.
Using machine learning algorithms, scientists compared individual protein spectra with age-adjusted mean, assigning biological age to each organ. One third of the participants had at least one organ classified as “extremely aged” or “extremely young”—with a standard deviation of more than 1.5 compared to typical aging patterns.
Major disease associations emerged:
- Older heart forecasts a 75% increase in risk of atrial fibrillation and 83% increase in risk of heart failure
- Elderly lungs are associated with an increased risk of COPD in 39%
- Older kidneys are associated with a 66% increase in risk of chronic kidney disease
- Elderly brains show the strongest prediction of Alzheimer’s disease
Accumulation effect
Having multiple aging organs can greatly increase the risk of death. People with 2-4-year-old organs have a 2.3-fold increase in death risk for older organs, while those with 5-7-year-old organs have a 4.5-fold increase in death risk. The risk of mortality in people with 8 or more elderly organs increased by 8.3 times, with 60% of whom died within 15 years.
However, not all young organs provide protection. Only the young brain and immune system can greatly reduce the risk of mortality. People with young brains and immune systems showed the strongest protection, with a 56% reduction in death risk.
Molecular insight into brain aging
The signature of brain aging reveals unexpected findings about white matter deterioration. About half of the brain aging proteins are derived from oligodendrocytes, which produce myelin, a fat insulation material around nerve fibers. This suggests that white matter degeneration plays a crucial role in brain aging.
Key brain aging proteins include the neural filament chain (NEFL), a marker of nerve damage used in clinical trials, as well as glial fibrillary acidic protein (GFAP), indicating an inflammatory brain response. The analysis also highlights the specific structures that are involved in the peripheral neuronal network-stabilizing brain connections.
Interestingly, plasma-based brain age is only weakly associated with MRI-based brain age measurements, suggesting that they capture different aspects of brain aging. “MRI brain age captures global cell loss, while plasma brain age captures molecular changes related to cell states and interactions,” the researchers noted.
Lifestyle and intervention potential
Organ age measurements respond to lifestyle factors. Smoking, drinking and processing meat intake accelerates organ aging, while exercise, fish consumption and higher education promote young organ profiles. Certain drugs, including estrogen therapy and anti-inflammatory drugs, are also associated with the age of young organs.
Wyss-Coray would envision using these measurements to test anti-aging interventions before the disease progresses. “This approach may lead to human experiments testing the effects of new lifespan interventions on the biological age of individual organs,” he explained.
The technology may be commercially available within 2-3 years and may shift from treating disease to preventing them by monitoring organ health decades before symptoms appear. As healthcare moves towards personalized prevention, blood organ aging is a promising tool for extending health and longevity.
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