Aging biomarkers are crucial for quantifying molecular, physiological, or functional features that vary among individuals as they age. They may enhance the prediction of health outcomes beyond mere chronological age. In this study published in Aging Cell, researchers explored the relationship between multimodal ageing biomarkers and plasma proteomic signatures associated with all-cause mortality.
The study focused on the Lothian Birth Cohort 1936 (LBC1936), which included 861 participants, of whom 444 had died over a 16-year follow-up period. The researchers employed Cox regression to analyze the association of various biomarkers with mortality risk. These biomarkers included the epigenetic clock GrimAge2, telomere length, physical function measures (such as grip strength, walking time, and respiratory function), neuroimaging, and cognitive assessments.
Among the proteomic organ clocks evaluated, accelerated ageing of the liver, immune system, and heart were notably linked to increased mortality risk, with hazard ratios (HR) indicating a significant association (liver: HR = 1.43, immune: HR = 1.42, heart: HR = 1.38). However, older epigenetic age, smaller total brain and grey matter volumes, reduced respiratory function, and poorer cognitive performance showed even stronger associations with mortality, with hazard ratios ranging from 1.44 to 1.62.
In addition to benchmarking the proteomic organ clocks, the study also conducted survival analyses on 9703 plasma protein targets, identifying 368 candidates associated with mortality. The 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 proteomic candidates with significant associations to mortality risk (GDF15: HR = 1.56, WFDC2: HR = 1.47, TIMP1: HR = 1.45).
This research provides a systematic benchmarking of proteomic organ clocks against established ageing biomarkers, highlighting the importance of various biological functions and proteins in relation to mortality risk.
What this study does not show
This study does not establish causation between the identified biomarkers and mortality, nor does it provide specific clinical applications for these findings.
Evidence scorecard
- Analytic validity: Established
- Clinical validity: Partial
- Clinical utility: Not established