Aging, a universal process with heterogeneous organ aging rates (not just psychological), is explored in a Nature Medicine study of ~45,000 people’s blood proteins. It first enabled non-invasive assessment of 11 organs’ aging, finding brain/immune system "youthfulness" key to longevity—e.g., a "young brain" protects against Alzheimer’s like two APOE2 genes. The study used plasma proteomics and organ-specific proteins to build aging-prediction models, noting low inter-organ age correlation, higher disease/mortality in multi-organ aging, and lifestyle’s molecular "aging imprints," with healthy habits linking to younger organs—providing personalized anti-aging metrics and scientific basis for "refusing to admit old age."
Imagine looking in the mirror and seeing a face that seems to defy your birth certificate, yet feeling fatigued or foggy-headed more often than you’d like. The truth is, aging isn’t just a matter of how we look or feel—it’s a complex biological process unfolding at different paces within each of our organs. One person’s liver might be as resilient as a 30-year-old’s, while their brain shows signs of aging typical of someone a decade older.
Aging is not merely a psychological perception but a reality where the "biological age" of each organ in our bodies deteriorates at varying speeds.
Recently, a groundbreaking study published in the journal Nature Medicine analyzed the blood proteins of nearly 44,500 individuals and, for the first time, achieved the assessment of the aging status of 11 organs through blood tests. Surprisingly, researchers discovered that the "youthfulness" of the brain and immune system is actually a key predictor of longevity! For instance, a "young brain" provides protection against Alzheimer's disease comparable to carrying two copies of the APOE2 protective gene.
Does it suddenly make you feel that "refusing to admit old age" may not be blind confidence but a kind of science?
Why Conduct This Study?
Aging is an inevitable process for all living organisms, but the aging rate of different organs is inconsistent. Some people have a young liver but an prematurely aging brain; others have a heart that’s still "dancing" while their kidneys have already "retired". How to accurately and non-invasively evaluate the biological age of different organs has long been a core challenge in the field of anti-aging.
This study aims to use plasma proteomics technology to construct a machine learning model based on the levels of organ-specific proteins in the blood to predict the biological age of 11 organs and explore its relationship with the risk of future disease occurrence and death.
Study Subjects and Procedures
Researchers analyzed plasma samples from 44,498 volunteers aged 40–70 in the UK Biobank and detected approximately 2,916 proteins. Moreover, they constructed an "organ age model" through the following steps:
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Identify organ-specific proteins: Using tissue RNA expression data from the GTEx database, screen for proteins whose expression level in a certain organ is at least 4 times higher than that in other organs (such as neurofilament light chain NEFL from the brain).
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Train an age prediction model: Use a LASSO regression model to predict an individual’s actual age based on the levels of these proteins.
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Calculate the "age gap": The difference between the predicted age and the actual age, which is standardized to obtain the "z-scored age gap". A positive value indicates that the organ is "aging", while a negative value indicates "youthfulness".
In addition, they also established a "systemic aging model" (using non-organ-specific proteins) and a "conventional aging model" (using all proteins) for comparison.
Figure 1. Plasma-based biological organ age model
Organ Age Gap is Independent and Stable
The study results showed that the biological ages of different organs have a very low correlation with each other (average r=0.21), meaning each organ indeed "ages on its own". For example, a person’s heart may have obviously aged, while their kidneys remain relatively young.
Based on this heterogeneity of organ aging, the research team further divided the population into categories such as "extreme agers" and "multi-organ agers". It is worth noting here that more than a quarter of the participants were classified as "multi-organ agers", and this group showed a significantly higher risk of illness and death in subsequent follow-ups. This finding reveals for the first time at the system level that the asynchrony of aging between organs is closely related to its profound impact on health outcomes.
In addition to evaluating organ age, the research team further explored the potential of these indicators to predict future disease occurrence, and the results were very striking. As shown in the figure below, by analyzing the 2 to 17 years of health records of the participants, they found that the biological age of organs is highly correlated with the incidence of various chronic diseases. Specifically, for every one standard deviation increase in brain aging, the risk of Alzheimer’s disease increases by about 1.8 times; if the brain is in an "extremely aging" state, the risk rises to 3.1 times, which is equivalent to carrying one APOE4 high-risk allele. Conversely, if the brain is "extremely young", the disease risk is significantly reduced by 74%, and the protective effect is comparable to carrying two APOE2 protective genes.
Brain and Immune System Status are Keys to Health and Longevity
In addition, the data also showed that simultaneous aging of multiple organs will significantly increase the risk of various diseases, while maintaining a young state of multiple organs—especially the brain, immune system, and intestines—can effectively reduce the incidence of diseases such as diabetes, chronic kidney disease, and osteoarthritis!
Furthermore, the analysis results confirmed that lifestyle leaves a profound "aging imprint" at the molecular level. Bad habits such as smoking, drinking, lack of exercise, frequent intake of processed foods, or insufficient sleep are significantly associated with accelerated aging of multiple organs. On the contrary, people with high education levels, regular exercise, and a diet rich in fatty fish, fresh fruits, and vegetables tend to have "younger" organs. Even some commonly used drugs and supplements—such as ibuprofen, vitamin C, cod liver oil, and multivitamins—were found to be associated with the young state of the brain, kidneys, or pancreas. All this shows that daily choices really do have a tangible impact on our physiological age.
Even more notably, the number of "aging organs" in the body shows a clear positive correlation with mortality risk. Even if only one organ is significantly aging, the risk of death increases by 1 to 3 times; if multiple organs age simultaneously, the risk rises in a stepwise manner. However, the study also points out that not all "young organs" confer a survival advantage—only a young brain or a young immune system is significantly associated with a lower mortality risk. If both remain young, the individual's survival advantage becomes even more pronounced! In other words, the brain and immune system are likely the core representatives of the body's overall health status, and their vitality is truly the "foundation of longevity"!
Figure 2. Organ age predicts disease onset
Summary
In conclusion, this study not only has breakthrough significance at the scientific level but also brings many inspirations to real life. It provides a quantifiable and trackable indicator system for "personalized anti-aging"—with just a tube of blood, we can predict organ health, disease risk, and even lifespan. Compared with traditional blood tests such as renal function or inflammatory indicators, these protein models are more comprehensive, forward-looking, and better able to capture tiny but key physiological changes.
The work published by the same team in Nature in 2023 [2] first proved that plasma proteins can reveal the aging characteristics of organs, and this new study further builds on this foundation by directly linking "organ aging" to longevity. At the same time, this study also echoes the Whitehall II cohort study [3] published in The Lancet Digital Health in 2025, which emphasizes the prediction of disease risk by different organ aging characteristics. Together, the three gradually outline a clear blueprint: through plasma proteomics, humans are expected to identify risks in advance before aging becomes apparent and find opportunities for intervention.
Of course, the study also has certain limitations. For example, the attribution of proteins to organs is indirectly inferred based on RNA expression and still needs further experimental verification; the data is mainly from the European population, and there may be differences in other ethnic groups; and the "extremely young" organ state is not always healthier, and there may be a case of "too much of a good thing". The researchers also pointed out that in the future, it is necessary to combine long-term follow-up, multi-ethnic samples, and intervention experiments to fully verify the practicality and accuracy of these models.
However, overall, this study marks a step forward in our journey towards "scientific anti-aging". In the future, we may no longer need complex invasive examinations. Only through regular blood proteome analysis can we determine whether our brain and immune system are still "functioning well", truly realizing active management of healthy aging.
References
- Oh, H. S.-H. et al. Plasma proteomics links brain and immune system aging with healthspan and longevity. Nat. Med. 31, 2703–2711 (2025).
- Oh, H. S.-H. et al. Organ aging signatures in the plasma proteome track health and disease. Nature 624, 164–172 (2023).
- Kivimäki, M. et al. Proteomic organ-specific ageing signatures and 20-year risk of age-related diseases: the Whitehall II observational cohort study. Lancet Digit. Health 7, e195–e204 (2025).