You might recall the development a few years ago of a proteomic aging clock that provided estimates of biological age for various organs in the body, rather than simply one overall measure. It was noted that individuals tended to have a distribution of biological ages across various organs, an individual’s organs age to different degrees. Here, researchers apply that clock to a subset of the UK Biobank population, and find that it produces the expected results. A higher predicted biological age for a given organ resulting from the clock algorithm correlates with a higher future risk of age-related disease in that organ, and the more organs exhibiting accelerated biological age, the greater the risk of mortality.
Plasma proteins derived from specific organs can estimate organ age and mortality, but their sensitivity to environmental factors and their robustness in forecasting onset of organ diseases and mortality remain unclear. To address this gap, we estimate the biological age of 11 organs using plasma proteomics data (2,916 proteins) from 44,498 individuals in the UK Biobank.
Organ age estimates were sensitive to lifestyle factors and medications and were associated with future onset (within 17 yearsʼ follow-up) of a range of diseases, including heart failure, chronic obstructive pulmonary disease, type 2 diabetes, and Alzheimer’s disease. Notably, having an especially aged brain posed a risk of Alzheimer’s disease (hazard ratio, HR = 3.1) that was similar to carrying one copy of APOE4, the strongest genetic risk factor for sporadic Alzheimer’s disease, whereas a youthful brain (HR = 0.26) provided protection that was similar to carrying two copies of APOE2, independent of APOE genotype.
Accrual of aged organs progressively increased mortality risk (2-4 aged organs, HR = 2.3; 5-7 aged organs, HR = 4.5; 8+ aged organs, HR = 8.3), whereas youthful brains and immune systems were uniquely associated with longevity (youthful brain, HR = 0.60 for mortality risk; youthful immune system, HR = 0.58; youthful both, HR = 0.44). Altogether, these findings support the use of plasma proteins for monitoring of organ health and point to the brain and immune systems as key targets for longevity interventions.
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