A major study of nearly 45,000 people in the UK has found that a youthful brain and immune system are the most powerful predictors of long life, more so than any other organ or conventional ageing marker. The research, which used advanced plasma proteomics to measure the biological age of organs, also revealed that ageing in the brain increases the risk of Alzheimer’s disease to a degree comparable to carrying a high-risk genetic variant. The findings were published in the journal Nature Medicine.
Scientists analysed blood samples from participants in the UK Biobank to estimate the biological age of 11 organs. By looking at over 2,900 plasma proteins specific to each organ, researchers developed a method to detect signs of ageing at the molecular level. Individuals whose organs showed accelerated ageing were more likely to develop diseases such as heart failure, kidney disease, type 2 diabetes, and chronic lung conditions.
The most striking finding was that people with an aged brain were over three times more likely to develop Alzheimer’s disease. This risk level was equivalent to carrying one copy of the APOE4 gene, the most established genetic risk factor for the condition. In contrast, individuals with a biologically younger brain had a substantially lower risk, similar to those with two copies of the protective APOE2 variant.
Beyond dementia, brain ageing was strongly linked to overall mortality. Those with an aged brain faced a 59% higher risk of death. A youthful brain, on the other hand, reduced mortality risk by 40%. When paired with a youthful immune system, the protective effect was even more pronounced, suggesting that these two systems may play a central role in regulating health across the body.
The researchers also observed that as the number of aged organs increased, so did the risk of death. Individuals with eight or more aged organs were over eight times more likely to die within 15 years than those with typical ageing profiles. However, youthful ageing across multiple organs did not offer the same protective benefit, highlighting the unique role of the brain and immune system in human longevity.
Importantly, the study showed that biological ageing was influenced by lifestyle. Smoking, alcohol intake, processed meat consumption, and poor sleep were linked to accelerated ageing in various organs. In contrast, exercise, oily fish consumption, and vitamin supplements such as cod liver oil and vitamin C were associated with youthfulness, particularly in the brain and kidneys.
These findings suggest that blood tests measuring specific proteins could one day offer early warnings of organ decline and help target longevity interventions. By identifying people at higher risk of disease based on organ ageing, clinicians may be able to intervene earlier and more precisely than is currently possible with standard diagnostics.
The study positions brain and immune system health as key targets in efforts to extend not only lifespan but healthspan: the number of years a person lives in good health.