Aging biomarkers are crucial 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 enabled researchers to estimate the biological ages of various human organs.
In this study, published in Aging Cell, the authors aimed to benchmark proteomic organ clocks against established multimodal ageing biomarkers to assess their associations with all-cause mortality. The research utilized data from the Lothian Birth Cohort 1936 (LBC1936), involving 861 participants and tracking 444 deaths over a 16-year period.
What this study does not show
This study does not establish a direct causal relationship between the identified biomarkers and mortality, nor does it provide specific clinical recommendations based on the 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 identified several biomarkers, including the epigenetic clock GrimAge2, telomere length, and various measures of physical and cognitive function, which were associated with mortality risk. Among the proteomic clocks, accelerated ageing of the liver, immune system, and heart were notably linked to increased mortality risk. However, older epigenetic age, reduced brain volume, and poorer respiratory function showed stronger associations with mortality.
Furthermore, survival analyses of 9703 plasma protein targets revealed 368 candidates associated with mortality. High-risk proteins were predominantly linked to immune functions, while low-risk proteins were associated with genomic stability and cellular maintenance. Notable proteomic candidates included GDF15, WFDC2, and TIMP1, which were significantly associated with mortality risk.
This systematic benchmarking of proteomic organ clocks against established ageing biomarkers provides valuable insights into the biological functions associated with mortality risk, although further research is necessary to explore clinical applications.