Aging biomarkers are crucial for understanding health outcomes as individuals age. They quantify various molecular, physiological, or functional features that differ among individuals, potentially enhancing predictions of health outcomes beyond mere chronological age. In this study published in Aging Cell, researchers investigated the relationship between plasma proteomic signatures and established ageing biomarkers in relation to all-cause mortality.
The study involved participants from the Lothian Birth Cohort 1936 (LBC1936), comprising 861 individuals, of whom 444 had died over a 16-year follow-up period. The researchers employed Cox regression analysis to assess the associations between various biomarkers and mortality risk.
Among the biomarkers evaluated were the epigenetic clock GrimAge2, telomere length, physical function measures such as grip strength and respiratory function, as well as neuroimaging and cognitive assessments. Notably, the study found that accelerated ageing in specific organs—particularly the liver, immune system, and heart—was significantly associated with increased mortality risk. For instance, the hazard ratios for accelerated liver, immune, and heart ageing were 1.43, 1.42, and 1.38, respectively.
However, other factors showed even stronger associations with mortality. Older epigenetic age, reduced brain volumes, diminished respiratory function, and poorer cognitive performance were linked to hazard ratios ranging from 1.44 to 1.62, indicating a higher risk of mortality.
In addition to the organ clocks, the study also analyzed 9703 plasma protein targets, identifying 368 proteins associated with mortality. The findings highlighted that high-risk proteins were predominantly involved in immune functions, while low-risk proteins were associated with genomic stability and cellular maintenance. Notable candidates included GDF15, WFDC2, and TIMP1, with hazard ratios of 1.56, 1.47, and 1.45, respectively.
This research provides a systematic benchmarking of proteomic organ clocks against established ageing biomarkers, offering insights into proteins and biological functions that may influence mortality risk.
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 specific recommendations for clinical practice.
Evidence scorecard
- Analytic validity: established
- Clinical validity: partial
- Clinical utility: not established