Aging biomarkers are essential for quantifying molecular, physiological, or functional features that vary among individuals as they age. These biomarkers can potentially enhance the prediction of health outcomes beyond just chronological age. Recent advancements in plasma proteomics have allowed researchers to estimate the biological ages of various human organs, providing a new avenue for understanding age-related health risks.
In this study, published in Aging Cell, the authors aimed to benchmark proteomic organ clocks against established multimodal ageing biomarkers. The research utilized data from the Lothian Birth Cohort 1936 (LBC1936), which included 861 participants and tracked 444 deaths over a 16-year period. The biomarkers assessed included the epigenetic clock GrimAge2, telomere length, physical function measures (such as grip strength and respiratory function), neuroimaging results, and cognitive assessments.
Among the findings, accelerated ageing of the liver, immune system, and heart was significantly associated with increased mortality risk, with hazard ratios (HR) indicating a strong correlation. Notably, the study found that older epigenetic age, smaller brain volumes, reduced respiratory function, and poorer cognitive performance had even stronger associations with mortality risk.
Furthermore, survival analyses of 9703 plasma protein targets identified 368 proteins linked to mortality. High-risk proteins were primarily associated with immune functions, while low-risk proteins were related to genomic stability and cellular maintenance. Key candidates identified included GDF15, WFDC2, and TIMP1, which showed significant associations with mortality risk.
This research provides a comprehensive benchmarking of proteomic organ clocks against established ageing biomarkers, revealing critical insights into the proteins and biological functions associated with mortality risk. The findings underscore the importance of integrating multimodal approaches in understanding the complexities of ageing and health outcomes.
What this study does not show
This study does not establish a causal relationship between the identified biomarkers and mortality risk, nor does it provide evidence for clinical utility in a practical setting.
Evidence scorecard
- Analytic validity: Established
- Clinical validity: Established
- Clinical utility: Not established