Aging biomarkers are essential for quantifying the molecular, physiological, or functional features that vary among individuals as they age. These biomarkers can enhance the prediction of health outcomes beyond mere chronological age. In recent research, plasma proteomics have been utilized to estimate the biological ages of various human organs, providing insights into the aging process.
The study in question, published in Aging Cell, aimed to benchmark proteomic organ clocks against established multimodal ageing biomarkers to assess their associations with all-cause mortality. The research was conducted on the Lothian Birth Cohort 1936 (LBC1936), which included 861 participants, of whom 444 had died over a 16-year follow-up period.
What this study does not show
While the study identifies associations between various biomarkers and mortality risk, it does not establish causation or provide specific interventions based on these findings.
Evidence scorecard
- Analytic validity: established
- Clinical validity: established
- Clinical utility: not established
The evidence is based on primary research involving human participants.
The study found that accelerated ageing of the liver, immune system, and heart was significantly associated with increased mortality risk. Specifically, the hazard ratios (HR) indicated that accelerated liver ageing had an HR of 1.43, immune ageing 1.42, and heart ageing 1.38, suggesting a strong correlation with mortality risk. However, the strongest associations were observed with older epigenetic age, smaller total brain and grey matter volumes, reduced respiratory function, and poorer cognitive performance, with HRs ranging from 1.44 to 1.62.
Furthermore, survival analyses of 9703 plasma protein targets identified 368 proteins associated with mortality risk. High-risk proteins were predominantly linked to immune functions, while low-risk proteins were associated with genomic stability and cellular maintenance. Notably, GDF15, WFDC2, and TIMP1 emerged as leading candidates linked to increased mortality risk, with hazard ratios of 1.56, 1.47, and 1.45, respectively.
This comprehensive study provides a systematic benchmarking of proteomic organ clocks against established ageing biomarkers, highlighting the importance of specific proteins and biological functions in relation to mortality risk. The findings underscore the complexity of aging and the potential for proteomic analysis to enhance our understanding of health outcomes in older adults.