Plasma Proteomics and the Secrets of Ageing: Why the Brain and Immune System Matter Most

Ageing is a universal experience, yet its pace and impact differ dramatically between people. While medicine has helped us live longer, questions remain about what truly governs the length of our healthspan—the years lived in good health. A recent study in Nature Medicine has provided powerful new insights, showing that the condition of our brain and immune system may hold the key to longevity.

By analysing plasma proteins from over 44,000 participants in the UK Biobank, researchers estimated the biological age of eleven organs, including the brain, immune system, heart, liver and kidneys. These proteins, circulating in our blood, act like molecular messengers from different tissues. When combined with machine learning, they reveal how “old” or “young” an organ is compared to peers of the same chronological age.

The results were striking. People with an “aged brain” had a threefold greater risk of developing Alzheimer’s disease, a risk on par with carrying a copy of the APOE4 gene, the strongest known genetic risk factor for dementia. By contrast, those with a “youthful brain” enjoyed protection equivalent to carrying two copies of APOE2, the rare but powerful protective genotype. The immune system also emerged as a crucial determinant: individuals with a youthful immune profile consistently showed lower mortality and greater resistance to chronic disease. Together, a youthful brain and immune system cut the risk of death by more than half.

The study also showed that organs do not all age at the same rate. Some people may have a young heart but an old liver, or a resilient brain alongside frail kidneys. The accumulation of aged organs compounded risk: those with eight or more aged organs faced mortality rates more than eight times higher than those with predominantly youthful profiles. In other words, while ageing is systemic, it is also uneven, and certain organs carry more weight in determining long-term health.

These findings resonate with what we already know from decades of ageing research. A review in Signal Transduction and Targeted Therapy reminds us that processes such as genomic instability, telomere shortening, mitochondrial decline and chronic inflammation underlie tissue dysfunction across the body. Yet the new plasma proteomics study goes further, pinpointing which organs most decisively shape our health trajectory.

The implications are profound. If we can maintain the youthfulness of the brain and immune system—whether through lifestyle, targeted therapies, or emerging interventions like rapamycin or plasma-derived treatments—we may not only add years to life but life to years. Plasma proteomics also promises to become a practical tool in medicine, allowing doctors to monitor biological ageing and anticipate disease risk before symptoms appear.

Ageing remains complex, influenced by genes, environment and chance. But the message from these findings is clear: protecting the brain and immune system could be the cornerstone of a longer, healthier life.

References

1. Oh HS-H, Le Guen Y, Rappoport N, et al. Plasma proteomics links brain and immune system aging with healthspan and longevity. Nat Med. 2025;31:2703–2711. https://doi.org/10.1038/s41591-025-03798-1 s41591-025-03798-1
   
2. Guo J, Huang X, Dou L, et al. Aging and aging-related diseases: from molecular mechanisms to interventions and treatments. Signal Transduct Target Ther. 2022;7:391. https://doi.org/10.1038/s41392-022-01251-0 s41392-022-01251-0