Why Your Brain May Be Older Than Your Heart: A New Way to Measure How We Age
Aging does not happen evenly across the body. While your passport age ticks forward at a steady pace, different organs may be wearing out faster—or more slowly—than others. A major new study published in Nature Aging suggests that this uneven “organ aging” is not only measurable but also strongly predicts disease risk and lifespan. Crucially, the researchers show that the brain’s biological age may matter more than any other organ when it comes to survival.
Beyond the Calendar: Measuring Biological Age
For decades, scientists have searched for reliable ways to measure biological aging—the gradual decline in function that increases vulnerability to disease. Previous “aging clocks” based on DNA methylation or clinical markers typically produce a single number for the whole body. While useful, these clocks miss an important reality: organs age at different rates.
Loss of protein balance, or proteostasis, is a hallmark of aging and closely tied to diseases such as Alzheimer’s, cardiovascular disease, and diabetes. Because proteins sit closer to biological function than genes, the plasma proteome—the thousands of proteins circulating in blood—offers a powerful window into how aging unfolds inside the body.
Building Organ-Specific Aging Clocks
Led by Yunhe Wang and colleagues, the research team analyzed blood samples from 43,616 participants in the UK Biobank, measuring nearly 3,000 plasma proteins. Using tissue-expression data, they identified proteins enriched in ten major organs, including the brain, heart, kidney, liver, immune system, and arteries.
Machine-learning models were then trained to predict age from these protein patterns. The result was not just one aging clock, but ten organ-specific clocks alongside a whole-body (organismal) clock. The models were validated in two independent cohorts: 3,977 participants from China and 800 from the US, showing striking consistency across populations (cross-cohort correlations of 0.98 and 0.93).
Aging at Different Speeds
The researchers calculated an “organ age gap”—the difference between a person’s predicted biological age and their actual chronological age. Positive gaps indicated accelerated aging; negative gaps suggested a “youthful” organ.
Importantly, age gaps across organs were only weakly correlated. In other words, having an “old” kidney did not necessarily mean having an “old” brain. This confirms that aging is not a single process but a mosaic unfolding differently across the body.
Predicting Disease Years in Advance
These organ-specific clocks proved to be powerful predictors of disease. In the UK Biobank, 65% of disease–organ associations remained significant even after adjusting for age, sex, lifestyle, and socioeconomic factors.
The brain clock stood out. For every one standard deviation increase in brain age gap, the risk of:
- All-cause dementia increased by 88% (hazard ratio, HR = 1.88),
- Multiple sclerosis by 52%, and
- Parkinson’s disease by 30%.
Brain aging was also the strongest predictor of death, with a 44% higher mortality risk per standard deviation increase—stronger than any other organ.
Other organs showed expected but revealing links. Accelerated kidney aging strongly predicted chronic kidney disease and type 2 diabetes, while heart and arterial aging tracked closely with cardiovascular disease. Notably, organ-specific clocks often outperformed whole-body aging measures, showing that focusing only on overall aging can hide critical risks.
The Power of a Youthful Brain
One striking finding involved people with “extreme” aging profiles. Participants with five or more extremely aged organs had a 7.8-fold higher risk of death than those without any. In contrast, those with multiple “super-youthful” organs had up to a 60% lower mortality risk.
The brain again played a central role. A youthful brain appeared to buffer genetic risk for Alzheimer’s disease, even among people carrying high-risk APOE4 variants. This suggests that biological brain aging may be a modifiable factor—offering resilience despite inherited vulnerability.
Lifestyle, Genes, and What Comes Next
Organ aging reflected both environmental and genetic influences. Unhealthy behaviors—smoking, physical inactivity, poor diet—were linked to faster aging, particularly in the brain and pancreas. Conversely, healthy lifestyles were associated with slower aging in several organs.
Genetic analyses identified brain-aging links to genes such as GABBR1 and ECM1, previously implicated in neurodegeneration and brain structure, pointing toward shared molecular pathways between aging and disease.
Toward Personalized Aging Medicine
By reducing some clocks to small, clinically feasible protein panels, the researchers move closer to real-world applications. In the future, a simple blood test could reveal which organs are aging fastest—long before symptoms appear.
This study reframes aging not as a single countdown, but as a complex, organ-by-organ process. And if there is one lesson above all, it is this: how old your brain is may matter more than how old you are.
The study is published in the journal Nature Aging. It was led by Andrew Chan from Brigham and Women's Hospital and Harvard Medical School, Boston, USA.
