An international team of researchers has created the most comprehensive set of organ-specific “ageing clocks” ever developed, and shown that having a healthier brain may reduce your risk of dementia and early death. The findings, published in Nature Aging, reveal that the pace of ageing varies from organ to organ and predicts disease risk and longevity.
“Ageing clocks” are statistical models that enable measurements of biological age compared to chronological age. These tools estimate how fast a person’s organs are ageing compared to the expected ageing.
Ageing is not a single process. Instead, the brain, arteries, kidneys and other organs each follow their own ageing timeline. The organ-by-organ approach offers a powerful new way to understand why people of the same chronological age can have very different health outcomes.
The team from the UK (Oxford Population Health), USA (Broad Institute) and China (Peking University) combined data on proteins found in blood from participants in UK Biobank with genetic and tissue-level information from the US Genotype-Tissue Expression (GTEx) project. The models were validated using the China Kadoorie Biobank and the US Nurses’ Health Study.
Key findings:
- Ageing of the brain and arteries showed the strongest influence on overall biological ageing.
- Kidney and intestine ageing predicted kidney disease and type 2 diabetes better than traditional biomarkers.
- Organ ageing also indicated risk of heart attack, stroke, depression, sleep disorders and chronic liver disease.
- People whose organs aged faster faced significantly higher risk of early death.
- The ageing clocks performed consistently across the diverse populations, showing that the clocks can be used to predict disease risk in different settings.
Brain ageing:
- The brain ageing clock was used to assess Alzheimer’s disease risk across people with different genetic risks of dementia based on their APOE genotypes; a youthful brain appears to confer resilience to the increased risk of dementia in those who carry the APOE4 variant.*
- Brain ageing is associated with death from diseases outside the brain, highlighting the association between ageing in the brain and the rest of the body, as well as with typical brain diseases including neurodegeneration, neuroimmunology, and poor mental health.
- Brain ageing also contributes to health span (the part of a person’s life during which they are in generally good health).
- Brain ageing is determined by genetic drivers and unhealthy behaviours that accelerate ageing; a healthy lifestyle (such as non-smoking, and regular physical activity) is linked to slower ageing in organs such as the brain and intestine.
Cornelia van Duijn, St Cross Professor of Epidemiology at Oxford Population Health and co-author of the paper, said ‘Our study highlights the key role of the brain in our health and life expectancy. As a genetic neuro-epidemiologist, the finding that thrills me most is that managing your brain ageing may counteract any disadvantage based on your genetic make-up. This is a break through and worth the effort.’
The researchers also attempted to uncover mechanisms by which organ-ageing can lead to diseases. They found that both brain and artery ageing are linked to synaptic loss (impairment of communication between neurons), vascular dysfunction and glial activation (which are involved in coordinating the response to inflammation) – known risk factors for cognitive decline and dementia.
Zhengming Chen, Richard Peto Professor of Epidemiology at Oxford Population Health and senior author of the paper, said ‘Ageing is a complex process, shaped by genetic, environmental and lifestyle factors. Our proteomic ageing clocks give us a powerful new framework for understanding ageing and predicting disease risk across diverse populations. This opens the door to earlier interventions and healthier, longer lives for people around the world.’
‘Our findings substantially extend the concept of organ-specific ageing clocks to diverse populations,’ said first author and corresponding author Yunhe Wang, a research fellow at Harvard University, and former DPhil student at Oxford Population Health. ‘The consistency of these organ-ageing patterns, and their ability to predict disease and longevity across populations, gives us confidence that they reflect fundamental biology.
‘A key insight is that different diseases are shaped by different patterns of organ ageing — brain ageing is closely linked to neurodegenerative risk, while other chronic physical diseases arise from the combined ageing of multiple organ systems. Understanding this multi-organ ageing-disease network through the lens of organ-specific ageing clocks will be crucial for guiding more personalised approaches to disease prevention and healthy ageing.’
Sihao Xiao, co-first author and former DPhil student at Oxford Population Health, added ‘This study was only possible thanks to large, long-term cohorts from both UK and Chinese populations, coordinated through Oxford Population Health, where we could follow participants for many years and link a single blood test to their future health. Seeing the same organ-ageing signals across such different populations gives us confidence that these proteomic clocks are robust and brings us a step closer to guiding personalised prevention in the near future.’
* APOE4 is the most common of four versions of the apolipoprotein E (APOE) gene, and has been associated with a higher risk of Alzheimer’s.