A research group assessed plasma proteins between 1997 and 1999 from over 6200 middle-aged (45-69 years) individuals. They followed these people for 20 years and tracked 45 age-related diseases and multi-morbidity. They used SomaScan version 4.0 and 4.1. In addition to proteins for overall organismal age, they had clusters of proteins for arteries, brain, heart, immune system, intestine, kidney, liver, lung and pancreas.
“[Results] Over 123 712 person-years of observation (mean follow-up 19·8 years [SD 3·6]), and after excluding disease cases at or before baseline, higher organ age gaps were associated with an elevated risk of 32 out of the 45 age-related diseases, with HRs per SD increment of 1·20 or higher after adjustment for age, sex, and ethnicity (figure 2A), and an elevated risk of 30 diseases after an additional mutual adjustment for organ-specific age gaps (figure 2B, appendix pp 25–27). For six diseases, we observed perfect organ specificity (ie, diseases that were only associated with the respective organ age gap): liver failure (age-adjusted, sex-adjusted, ethnicity-adjusted, and other age-gap-adjusted HR 2·13 per SD increment [95% CI 1·41–3·22] in the liver age gap), dilated cardiomyopathy (HR 1·65 per SD increment [1·28–2·12] in the heart age gap), chronic heart failure (HR 1·52 per SD increment [1·40–1·65] in the heart age gap), lung cancer (HR 1·29 per SD increment [1·04–1·59] in the lung age gap), agranulocytosis (HR 1·27 per SD increment [1·07–1·51] in the immune system age gap), and lymphatic node metastasis (HR 1·23 per SD increment [1·06–1·43] in the immune system age gap). Partial organ specificity (diseases associated with age gaps in the respective organ and other organs) was observed for 12 diseases, including chronic kidney disease and cirrhosis, each of which was associated with as many as four organ age gaps. Another 12 diseases were not associated with the respective organ age gap, suggesting no organ specificity. These included end-stage renal disease (linked to heart, immune system, liver, and brain age gaps), fatty liver (heart and arterial age gaps), viral infections (arterial age gap), diabetes (kidney and immune system age gaps), dementia (immune system age gap), and Parkinson’s disease (intestine age gap). [..]
Diseases of the pancreas, intestines, and nervous system were not associated with age gaps of the respective organ, suggesting no organ specificity for these organ age gaps. Individuals with a large organismal age gap had an increased risk of diseases of the kidneys, pancreas, nervous system, liver, immune system, intestines, and cardiovascular system.
[..] the findings of the associations between organ age gaps and multiorgan multimorbidity remained statistically significant after additional adjustments for smoking, alcohol consumption, physical activity, obesity, and socioeconomic status. We also found that the organismal age gap and age gaps in all organs except the intestines and brain were associated with total mortality. The age-adjusted, sex-adjusted, and ethnicity-adjusted HRs per SD higher age gap varied from 0·99 (95% CI 0·93–1·05) for the brain age gap to 1·23 (1·17–1·29) for the immune system age gap, with the strongest association evident for the organismal age gap (HR 1·30 [1·23–1·38]).
[Discussion] Our 20-year follow-up supports organ-specific ageing, as indicated by a distinct proteomic signature, as part of the aetiology of age-related morbidity. The findings suggest diverse, mostly partial organ specificity in the links between accelerated organ ageing and health outcomes. First, the rates of ageing between different organs showed only modest correlations, aligning with the notion that biological ageing progresses at slightly varying rates among different organs within the same individual. Second, individuals with a fast-ageing organ faced an increased risk of 30 out of the 45 age-related diseases examined. We observed strict organ specificity for only six diseases. In contrast, the likelihood of developing the other 24 diseases was influenced by age acceleration in both the respective organ and other organs, or solely by age acceleration in other organs. Third, individuals with fast-ageing lungs had a higher risk of developing lung diseases than those with age acceleration in other organs. Similar patterns were observed with fast-ageing hearts and cardiovascular diseases, fast-ageing immune systems and immune diseases, and fast-ageing livers and liver diseases. However, advanced ageing in other organs also increased the risk of these organ-specific disease outcomes. Fourth, advanced ageing in almost all organs was linked to a higher long-term risk of multiorgan multimorbidity. Most associations with single-organ multimorbidity were weaker. [..]
In our long-term follow-up, faster ageing of the immune system emerged as the strongest long-term risk factor for incident dementia, and faster ageing of the intestines was the strongest risk factor for Parkinson’s disease. These findings are consistent with longitudinal studies that have linked circulating inflammatory markers (such as C-reactive protein, IL-6, and α-1-antichymotrypsin) and severe peripheral systemic infections to a higher risk of dementia, and a compromised intestinal barrier, as part of the overall immune system, to Parkinson’s disease. Furthermore, recent proteome-wide analyses suggest a role for inflammation in the aetiology of neurodegeneration. [..]
A better understanding of these signatures could potentially offer tailored prevention strategies for age-related diseases, contribute to disease-specific risk calculators, facilitate new organ-specific therapeutic opportunities, provide prognostic information for individuals living with diseases, and offer intermediary outcomes for interventions aimed at reducing age-related diseases. Plasma-based organ age signatures are attractive due to their quick and easy assessment, whereas existing methods to study individual organs, such as tissue biopsies and imaging, are expensive, invasive, or require equipment not available in all health-care settings.”
Full article, M Kivimaki, P Frank, J Pentti et al. The Lancet Digital Health, 2025 March.