Identifying Plasma Proteins Associated with Mortality Risk and Biological Age
Researchers here report on the results of screening a few thousand proteins found in blood plasma for those where levels correlate with (a) risk of mortality and (b) organ-specific biological age, using a consensus approach to determining those biological age measures from proteomic data. The usual caveats apply regarding whether or not such an aging clock is actually measuring biological age, or would still produce decent data if an anti-aging intervention were involved, but gathering more data on the performance of such clocks is nonetheless a potentially useful activity.
We aimed to identify plasma proteins associated with all-cause mortality and determine their relationships with chronic disease burden and biological aging at both the organismal and organ-specific levels, thereby providing insights into the biological mechanisms underlying healthy aging and longevity. We conducted a prospective cohort study of 1,025 older adults from the LonGenity study, analyzing 4,265 plasma proteins. Associations between protein levels and all-cause mortality were evaluated using Cox proportional hazards regression over a mean follow-up of 8.05 years. Mortality-associated proteins were further examined for their relationships with chronic disease burden and proteome-derived measures of organismal and organ-specific biological aging. Findings were independently validated in 1,124 participants from the Baltimore Longitudinal Study of Aging (BLSA).
Seventeen plasma proteins were significantly associated with all-cause mortality. Higher levels of epidermal growth factor receptor (ERBB1) and anthrax toxin receptor 2 (ANTXR2) were associated with lower mortality risk and younger biological age across multiple organ systems. Conversely, higher levels of growth differentiation factor 15 (GDF15), human epididymis protein 4 (HE4), and insulin-like growth factor-binding protein 2 (IGFBP-2) were associated with increased mortality and older biological age across multiple organ systems. Specifically, elevated MIC-1 was associated with older organismal biological age, whereas ERBB1 was associated with younger liver biological age. These associations were independently replicated in the BLSA cohort.